Pelvic Floor:
CHAPTER 2 During parturition, the pelvic floor helps the anterior rotation of
Maternal Anatomy
Innominate Bones:
Each is formed by the fusion of 3 bones – ilium, ischium, pubis
Ilium: superior bone
ASIS – attachment to the inguinal ligament
PSIS – marks level of the 2nd sacral vertebra
Iliac crest: ASIS to PSIS
Ischium:
Body – forms part of the acetabulum
Superior ramus – posterior and inferior to the body
Inferior ramus – fuses with inferior ramus of pubis
Ischial spine – separates greater sciatic from lesser sciatic notch
Ischial tuberosity – inferior part of the ischium (where we sit)
Pubis:
Body – rough surface, joined to the opposite pubis = symphysis
pubis (levator ani are attached to the pelvic aspect of the pubis)
Pubic crest – superior border
Pubic tubercle – lateral end of pubic crest (inguinal ligament and
conjoined tendon are attached in pubic tubercle)
Superior ramus – meets body of the pubis at pubic spine and
body of ilium at iliopectineal line
Inferior ramus – merges with inferior ramus of ischium
LANDMARKS:
ILIOPECTINEAL LINE: extends from pubic tubercle back to
sacroiliac joint, forms greater part of the boundary of the pelvic
inlet
GREATER SACROSCIATIC NOTCH: between PSIS superiorly and
ischial spine inferiorly
LESSER SACROSCIATIC NOTCH: between ischial spines posteriorly
and ischial tuberosity inferiorly
OBTURATOR FORAMEN: delimited by the acetabulum, ischial
rami and pubic rami
Sacral promontory: anterior superior edge of first sacral vertebra,
it protrudes slightly into the cavity of the pelvis, reducing the AP
diameter of the inlet
Coccyx: coccygeus muscle, levator ani muscles and sphincter ani
externus are attached to anterior aspect of the coccyx (impt in
pelvic floor function)
Sacrococcygeal Joint: synovial hinge joint between 5th sacral and
first coccygeal vertebrae, allows both flexion and extension (by
increasing anteroposterior diameter of the outlet of the pelvis)
Mobility of the Pelvis:
Under the influence of progesterone and relaxin → increased
flexibility of sacroiliac joints and symphysis pubis (hyperemia and
softening of the ligaments around the joints also take place)
Pubic bones may separate 1-12mm
In adolescence, the pelvis changes from an anthropoid to a
gynecoid configuration
Smaller pelvic capacity in adolescent girls may contribute to
higher incidence of CPD and other dystocias in the primigravidous
girls <15 years old
the presenting part and directs it downward and forward along
the birth passage
LEVATOR ANI:
Origin:
1. Posterior side of pubis
2. Arcuate tendon of the pelvic fascia
3. Pelvic aspect of the ischial spine
Insertion (anterior to posterior)
1. Vaginal walls
2. Central point of perineum
3. Anal canal
4. Anococcygeal body
5. Lateral border of the coccyx
Pubococcygeus Muscle: MOST IMPORTANT, MOST DYNAMIC,
MOST SPECIALIZED PART OF THE PELVIC FLOOR
• Lies in the midline
• Perforated by the urethra, vagina and rectum
• Often damaged during delivery
• Origin: posterior side of the pubis
• Muscle passes posterior and medially in 3 sections: (1)
pubovaginalis (2) puborectalis, and (3) pubococcygeus
o Pubovaginalis: most medial section,
horseshoe shaped, open anteriorly, its fibers
make contact and bled with ms of urethral
wall then form a loop around the vagina); acts
as a sling for the vagina – MAIN SUPPORT OF
THE FEMALE PELVIC ORGANS (tearing or
overstretching predisposes pt. to uterovaginal
prolapse); when it goes into spasm –
vaginismus
o Puborectalis MS: forms a loop around the anal
canal and rectum
▪ Insertion is into the lateral and
posterior walls of the anal canal
between the sphincter ani internus
and externus
▪ Suspends the rectum
▪ Controls descent of feces
o Pubococcygeus: most lateral fibers of the
pubococcygeus muscle, Y-shaped insertion
into the lateral margins of the coccyx; when it
contracts, it pulls the coccyx anteriorly
increasing the anorectal juncture, helps
control passage of feces
Iliococcygeus Muscle: arise from white line of pelvic fascia, join
with pubococcygeus muscle and inserts into lateral margins of
coccyx, less dynamic than pubovaginalis and act more like a
musculofascial layer
Ischiococcygeus Muscle: originate from ischial spines and insert
into the lateral borders of coccyx and fifth sacral vertebra;
supplement levators ani and occupy most the posterior portion of
the pelvic floor
When the presenting part of the fetus has reached the
proper level, the central point of the perineum becomes
thin, levator ani and anal sphincters relax, muscles of the
pelvic floor are drawn over the advancing head
PERINEUM
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Urogenital triangle:
1. Anteriorly: subpubic bone
2. Laterally: ischiopubic rami and ischial tuberosities
3. Posteriorly: transverse perineal muscles and base of the
urogenital diaphragm
• It contains:
o Opening of the vagina
o Terminal part of urethra
o Crura of the clitoris with the ischocavernosus
muscles
o Vestibular bulbs covered by bulbocavernosus
muscles
o Bartholin’s glands and their ducts
o Urogenital diaphragm
o Muscles that constitute the central point of
the perineum
o Perineal pouches (superficial and deep)
o BV, nerves, lymphatics
Urogenital Diaphragm:
Lies in the anterior triangle of the perineum and it contains:
• 2 muscles: deep transverse perineal and sphincter of
membranous urethra
• Superior layer of fascia (thin and weak)
• Inferior fascial layer – strong, fibrous membrane
PELVIC INLET
• Pelvic joints have limited degree of mobility
• During pregnancy → remarkable relaxation caused by
upward gliding of the sacroiliac joint
• May increase the diameter of the outlet by 1.5-2cm
• True conjugate: uppermost margin of the SP to the
sacral promontory
• Obstetrical conjugate: shortest distance between the
sacral promontory and symphysis pubis, 10cm (it
cannot be measured directly with examining fingers) →
thus you subtract 1.5-2cm from the diagonal conjugate
• Diagonal conjugate: distance from the lowest margin of
the symphysis to the sacral promontory
MIDPELVIS AND PELVIC OUTLET
• Levels of the ischial spines
• Interspinous diameter: 10cm (smallest pelvic diameter)
• Anteroposterior diameter: 11.5cm
SUPERFICIAL PERINEAL POUCH:
• Space that lies between the inferior layer of the
urogenital diaphragm and Colles fascia
• Superficial Transverse Perineal Muscles:
o Superficial parts of the deep muscles
o Have the same origin and insertion
o Outside the urogenital diaphragm
• Ischiocavernosus Muscles:
o Covers the clitoral crura
o Origin: inferior ramus of pubis
o Insertion: lateral aspect of the crus
o Compress the crura, blocks venous return →
erection of the clitoris
• Bulbocavernosus Muscle:
o Surrounds the vagina
o With the external anal sphincter, it makes a
figure eight around the vagina and rectum
o AKA Bulbospongiosus
o Origin: central point of the perineum
o Insertion: dorsal aspect of the clitoral body
o Compresses the erectile tissue around the
vaginal orifice and helps in clitoral erection by
compressing its dorsal vein
o Weak vaginal sphincter
o Real sphincter: pubovaginalis of the levator
ani
DEEP PERINEAL POUCH
• Lies between the two fascial layers of the urogenital
diaphragm
• Sphincter of the membranous urethra / compressor of
the urethra
• Deep transverse perineal muscles: lie between the
layers of the fascia of the urogenital diaphragm
o Origin: ischiopubic ramus on each side
o Insertion: central point of the perineum
2
 contractile portion; distention of the lower
segment dilates the cervix
ANAL TRIANGLE o Isthmus: small, constricted region of the
• Anterior: transverse perineal muscles and base of uterus; 5-7mm in length, lies superior to
urogenital diaphragm internal os of cervix
• Laterally: ischial tuberosities and sacrotuberous o Cervix: canal with an internal os superiorly
ligaments separating the cervix from the uterine cavity
• Posterior: coccyx and an external os inferiorly which closes off
• Contains: the cervix from the vagina; 2.5cm in length;
o Lower end of anal canal and its sphincters lower part pierces anterior wall of vagina and
o Anococcygeal body its tissue blends with that of the vagina
o Ischiorectal fossa Myometrium:
o BV, lymphatics, nerves • Where most growth takes place (in the myometrium of
the body and fundus)
PERINEAL BODY • First half of pregnancy: hyperplasia (formation of new
• Central point of the perineum or perineal body lies muscle fibers)
between the posterior angle of the vagina in front and • Second half of pregnancy: hypertrophy (enlargement of
the anus behind existing myometrial cells)
• Muscles that meet to form the perineum: • Individual myometrial fibers increase 10-fold during
o Sphincter ani externus pregnancy
o 2 levator ani muscles • At term: estimated number of cells: 200 billion
o Superficial and deep transverse perineal • Composed of 4 major proteins: myosin, actin,
muscles tropomyosin, troponin
o Bulbocavernosus muscle • Main stimulus to growth: 17 beta-estradiol
• During early pregnancy: uterine walls are thicker than in
the non-pregnant state → lumen becomes larger and
walls thinner
UTERUS • At end of 5th month: 3-5mm thick and remain so until
• Small, muscular organ composed of 3 layers: term
o Perimetrium: outer covering, serous • Late pregnancy: large, muscular sac with thin, soft and
peritoneal layer easily compressible walls → makes the corpus
o Myometrium: thick, middle layer made up of indentable and enables the fetus to be palpated
muscle fibers
o Endometrium: inner, mucous layer of glands Isthmus:
and supporting stroma attached to the • Lies between the body of the uterus and the cervix
myometrium • Boundaries are not well defined
• Myometrium is made up of 3 layers of muscle: • Non-pregnant uterus: 5-7mm long, it differs from the
o Outer layer: longitudinal fibers corpus in that it is free of mucus-secreting glands
o Inner layer: fibers run in a circular direction • Upper limit: constriction in the lumen of the uterus
o Thick middle layer whose fibers are arranged which marks the lower boundary of the body of the
in an interlacing pattern and through which uterus (anatomic internal os of Aschoff).
BV course • Lower limit: site of transition from the mucosa of the
• Shape: isthmus to the endocervical mucous membrane
o Non-pregnant: pear shaped (histologic internal os)
o 3rd month AOG: globular • As the uterus grows, isthmus increases in length to
o 7th month to term: pyriform about 25mm and becomes soft and compressible
• Size: • Hegar’s sign depends on palpation of the soft isthmus
o Non-pregnant: 7.5x5.0x2.5cm to 28 x 24 x between the body of the uterus above and the cervix
21cm below
o Weight: 30-60g to 1000g at end of pregnancy • Ovum implants in the upper part of the uterus → 3rd
o Changes from solid organ in the nullipara to a month: enlarging embryo grows into the isthmus which
large sac, capacity increasing form almost nil unfolds and expands to make room → eventually, the
to 4,000ml isthmus forms part of the lower uterine segment of the
• Location: uterus during labor → histologic internal os becomes
o Pelvis the internal os of pregnancy and the anatomic internal
o As it enlarges → extends into the abdominal os becomes the physiologic retraction ring of normal
cavity labor, stops when it reaches the cervix → 7th month:
• Uterine divisions: most of the enlargement takes place in the body and
o Fundus: part superior to the openings of the fundus and the uterus becomes pear shaped → onset
fallopian tubes of labor: lower uterine segment comprises about 1/3 of
o Body: main part, has thick walls, lies between the whole uterus
the tubal openings and the isthmus; main
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Cervix:
• Mostly of connective tissue interspersed with muscle
fibers
• Hard and fibrous in the non-pregnant state
• Softening is due to the increased vascularity, general
edema and hyperplasia of the glands
• Compound tubular glands become overactive = large
quantities of mucus → accumulates in the cervical canal
and thickens = mucus plug (seals off the canal from the
vagina and prevents ascent of bacteria into the uterine
cavity) plug is expelled early in labor
• End of gestation and during labor, internal os gradually
disappears and the cervical canal also becomes part of
the lower uterine segment leaving only the external os
Vagina:
• Fibromuscular membranous tube surrounded by the
vulva inferiorly, uterus superiorly and bladder
anteriorly, rectum posteriorly
• Direction: obliquely superior and posterior
• Cervix enters vagina through the anterior wall; hence,
the anterior wall of the vagina (6-8cm) is shorter than
the posterior wall (7-10cm)
• Protrusion of the cervix into the vagina divides the
vagina vault into 4 fornices: anterior, posterior, and two
lateral fornices - posterior fornix is much deeper than
•
the others
Walls of the vagina:
o Mucosa: epithelial layer
o Submucosa is rich in blood vessels
o Muscularis: 3rd layer
o Outer connective tissue layer connects the
vagina to the surrounding structures
NERVE SUPPLY
Pudendal Nerve:
• Formed from the anterior rami of S2-4 spinal nerves
• Courses between the piriformis and coccygeus muscles
and exits through the greater sciatic foramen at a
location posterior to the sacrospinous ligament and
medial to the ischial spine
• Landmark: ischial spine
• It then runs beneath the sacrospinous ligament (above
the sacrotuberous ligament) → lesser sciatic foramen to
course along the obturator internus
• Pudendal canal AKA Alcock canal (formed by splitting of
the obturator internus investing fascia)
UTERUS
• The lower portion of the anterior uterine wall is united
to the posterior wall of the bladder by a well-defined
loose connective tissue – the vesicouterine space
• Isthmus forms the lower uterine segment during
pregnancy
• 60 grams
• Pregnancy = hypertrophy
o Previously flattened fundus becomes dome
shaped
o Round ligaments appear to insert at the
junction of the middle and upper thirds of the
uterus
o Fallopian tubes elongate
o Ovaries appear grossly normal
Myometrium and Endometrium:
• Interlacing myometrial fibers surround myometrial
vessels and contract to compress the vessels which
helps in the hemostasis
CERVIX
• Ectocervix is lined by nonkeratinized stratified
squamous epithelium
• Endocervical canal: single layer of mucin secreting
columnar epithelium which creates glands
• Cervical stroma is composed mainly of collagen, elastin
and proteoglycans
• Pregnancy
o Increased vascularity → blue tint → Chadwick
sign
o Cervical edema leads to softening: Goodell
sign
o Isthmic softening: Hegar sign
LIGAMENTS
• Round ligament: corresponds Embryologically to the
male gubernaculum testis
o Below and anterior to the fallopian tubes
o Extends laterally and downward into the
inguinal canal to terminate in the upper
portion of the labia majora
o Sampson artery
o Non pregnant: 3-5mm → undergo
hypertrophy in and
• Broad ligament: 2 winglike structures that extend from
the lateral uterine margins to the pelvic sidewalls
o divide the pelvic cavity into anterior and
posterior compartments
• Cardinal ligament: “transverse cervical ligament” or
Mackenrodt ligament
o Thick base of the broad ligament
o Medially, it is united firmly to the uterus and
upper vagina
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BLOOD SUPPLY
• Uterine artery – main branch of the internal iliac artery
o Enters the base of the broad ligament and
makes its way medially to the side of the
uterus
o 2cm lateral to the cervix, the uterine artery
crosses over the ureter
o Once it reaches the supravaginal portion of
the cervix it divides → cervicovaginal artery:
lower cervix and upper vagina → main branch
turns upward and extends as a highly
convoluted vessel that traverses along the
lateral margin of the uterus
o Penetrates body of the uterus → arcuate
arteries → basal OR coiled spiral arteries
o Spiral arteries → functionalis layer
o Basal arteries / straight arteries → extend
into the basalis layer (not responsive to
hormonal influences)
• Ovarian artery
o Direct branch of the aorta
o Enters the broad ligament through the
infundibulopelvic ligament
o Supplies the fallopian tubes
• NERVE SUPPLY:
o Formed by sympathetic fibers arising from
spinal levels T10 – L2
o Parasympathetic innervation: S2-S4
o Combination of the 2 hypogastric nerves
(sympathetic) and 2 pelvic splanchnic nerves
(parasympathetic) = pelvic plexus
o Fibers of the plexus:
▪ Vesical plexus: innervates the
bladder and middle rectal travels to
the rectum
▪ Uterovaginal plexus “Frankenhäuser
plexus” reaches the proximal
fallopian tubes, uterus and upper
vagina
OVARIES
Anatomy
• Childhood: 2.5-5cm in length, 1.5 to 3cm in breadth and
0.6 x 1.5cm in thickness
• Lie in the upper part of the pelvic cavity
• Consists of the cortex and medulla
Ovarian Gametogenesis (oogenesis)
• Primordial germ cells (oogonia) migrate to the genital
ridge → meiotic division (primary oocytes) until they
reach the diplotene stage of the prophase (germinal
vesicular stage) → stay until stimulation by
gonadotropins in adulthood during the menstrual cycle
• Decline of primary oocytes due to process of apoptosis
and atresia of the enveloping follicle
• Oogonia:
o 2nd month of fetal life: 600,000
o 6th-7th month: 7million
• Ovarian follicles:
o Birth: 2-4 million
o 90% depleted by puberty
o 37 years old: 25,000
o 50 years old: 1000
Ovarian Folliculogenesis:
• Primary oocyte is surrounded by a single layer of
granulosa cells in a unit (primordial follicle) →
gonadotropin stimulation → primary follicle (multiple
layers of granulosa cells surround them)
o Occurs during the nonovulatory stages of
childhood
• Primary follicle → secondary or antral follicle → enters
the final stages of Folliculogenesis characterized by the
transition from intraovarian regulation to a major
control by the hypothalamic pituitary unit (requires
FSH)
• Only 400 follicles complete the process
PHYSIOLOGY
• FSH acts primarily on the granulosa cells of the
maturing
• antral follicle to stimulate follicular growth
• LH acts primarily on the theca cells to induce
steroidogenesis
• FSH and LH are transmembrane G protein coupled
receptors
• Upon binding of the receptor to the gonadotropin →
activation of G protein → G protein detaches from the
receptor → activates cAMP and dependent protein
kinases → catalytic units are released +
phosphorylation of proteins → activation of genes
Ovarian Steroid: Biosynthesis
• Production of ovarian steroids (occurs following binding
of both FSH and LH to their receptors)
• Ovary secretes THREE PRIMARY HORMONES
o Estradiol: primary estrogen
o Progesterone
o Androstenedione
• And other hormones:
o Estrone (less potent estrogen)
o Pregnenolone
o 17-hydroxyprogesterone
o dehydroepiandrosterone (DHEA)
• ALL STEROIDS ARE DERIVED FROM ACETATE which is
transformed into cholesterol
• STEPS:
o Cholesterol is transferred from the outer
mitochondrial membrane into the inner
membrane → cytochrome P450 → splits
cholesterol off the side chain → cholesterol is
now free (lipophilic) and is unable to cross the
membranes on its own → StAR (steroidogenic
acute regular protein) assists it
o Cholesterol → pregnenolone
▪ Hydroxylation of C-20 and C-22 and
cleavage reducing the C-27 into C-
21
5
 o 2 major pathways determine the capacity of the ovary
▪ Pathway through 17- to provide oocytes capable of being
hydroxypregnenolone and DHEA to fertilized
androstenediol • Measure FSH on day 2-3
▪ Pathway via progesterone and 17- of cycle
hydroxyprogesterone to the o High FSH:
androgens, androstenedione and ovarian aging →
testosterone fewer
recruitment of
follicles
• Antral follicle count
• Inhibin B day 2-3 of cycle
• Aromatase enzyme o The recruitment
o Converts androgens into estrogens, estrone of the follicle
or estradiol THROUGH THE LOSS OF THE C-19 cohort being
METHYL GROUP through OXIDATION reflected by an
o Estrogens are also synthesized in adipose INCREASE in this
tissue which in post-menopausal women hormone
becomes the major site of estrogen produced and
biosynthesis secreted
o In the ovary, the main androgen source is o Inhibin B levels
ovarian testosterone → main product is provide an early
estradiol indicator of the
o Adipose tissue the main androgen source is number of
circulating androstenedione (produced by the recruited
adrenals) → estrone follicles
o GREATER AMOUNT OF FAT PRESENT, THE • AMH
GREATER THE AMOUNT OF o Secretory
ANDROSTENEDIONE that is converted to product of
estrone via aromatase granulosa cells
• Ovarian Steroids: Blood Transport and Metabolism in preantral and
o After release into the circulation → sex small antral
steroids bind to a steroid specific transport follicles
protein known as the sex hormone binding
globulin (SHBG) which binds primarily adrenal
steroids to a lesser degree progesterone Fallopian Tubes:
• Prostaglandins • Extends 8-14cm from the uterine cornua
o Mediators of inflammatory and anaphylactic • Isthmus: 2-3mm
reactions • Ampulla: 5-8mm
o Most abundant precursor is arachidonic acid • Cross section:
o Help control early follicular growth by o Mesosalpinx: single cell mesothelial layer
increasing blood supply to certain follicles and functioning as the visceral peritoneum
inducing FSH receptors in granulosa cells or o Myosalpinx: smooth MS arrange din an inner
preovulatory follicles circular and outer longitudinal layer
MENSTRUAL CYCLE o Distal tube: 2 layers are less distinct and
• Follicular phase replaced near the fimbriated extremity by
• Luteal phase sparse interlacing muscular fibers
• Mean age of menarche: 12 yrs. old ▪ Undergoes rhythmic contractions
• Menopause: 45-55 years old o Endosalpinx: tubal mucosa
• FOLLICULAR PHASE ▪ Single columnar epithelium
o Recruitment of a Cohort of Antral Follicles: ▪ Ciliated and secretory cells resting
▪ FSH provides the critical signal for on a sparse lamina propria
the recruitment of a cohort of
preantral follicles
▪ FSH rescues the follicles from
programmed death
CHAPTER 3
▪ Start of the follicular phase is
characterized by a small but Congenital Genitourinary Abnormalities
significant increase in the FSH:LH
ratio GENITOURINARY TRACT DEVELOPMENT
▪ Ovarian reserve: the number of EMBRYOLOGY OF THE URINARY SYSTEM
antral follicles in the ovaries and

6
• Between the 3rd and 5th gestational weeks, an elevation
of intermediate mesoderm on each side of the fetus
known as the urogenital ridge, begins development into
the urogenital tract
• Urogenital ridge divides into the genital ridge (→ ovary)
and the nephrogenic ridge (→ mesonephros →
mesonephric kidney)
• Metanephros becomes the final kidney
• Early urinary tract develops from the mesonephros and
its mesonephric ducts
• Between the 4th and 5th weeks, each mesonephric duct
gives rise to a ureteric bud which grows cephalad to its
respective mesonephros
• As each bud lengthens it induces differentiation of the
metanephros (which will become the final kidney)
• Each mesonephros degenerates near the end of the
first trimester and without testosterone the
mesonephric ducts regress as well
• The cloaca begins as a common opening for the
embryonic urinary, genital and alimentary tracts
• By the 7th week, it becomes divided by the urorectal
septum to create the rectum and the urogenital sinus
• Urogenital sinus:
o Cephalad or vesicle → urinary bladder
o Middle or pelvic portion → female urethra
o Caudal or phallic part → distal vagina and to
the greater vestibular (Bartholin) and
paraurethral glands
EMBRYOLOGY OF THE GENITAL TRACT
• FT, uterus and upper vagina derive from the Mullerian
ducts (paramesonephric ducts – other term) which form
adjacent to each mesonephros
• These ducts extend downward and then turn medially
to meet and fuse together in the midline
• Uterus is formed by the union of the 2 Mullerian ducts
at the 10th week
• Fusion to create the uterus begins in the middle and
then extends both caudally and cephalad
• With cellular proliferation at the upper portion, a thick
wedge of tissues creates the characteristic piriform
uterine shape
• At the same time, dissolution of cells at the lower pole
forms the first uterine cavity
• As the upper wedge-shaped septum is slowly
reabsorbed, the final uterine cavity is usually formed by
the 20th week
• If the 2 Mullerian ducts fail to fuse → 2 separate
uterine horns remain
• Resorption failure of the common tissue between them
results in various degrees of persistent uterine septum
• Distal end of the fused Mullerian ducts comes in
contact with the urogenital sinus → endodermal
outgrowths from the sinus = sinovaginal bulbs →
sinovaginal bulbs proliferate and fuse to form the
vaginal plate → resorption of the vaginal plate forms
the vaginal lumen (which remains separated from the
urogenital sinus by the hymenal membrane which
further degenerates to leave only the hymenal ring)
• The close association of the mesonephric (Wolffian) and
paramesonephric (Mullerian) ducts explain the
abnormalities in their end-organs
• Anomalies frequently associated with renal defects:
o Unicornuate
o Didelphys
7
 o Agenesis syndrome
• Mesonephric ducts usually degenerate → persistent →
CHAPTER 4
Gartner duct cysts (located in the proximal
anterolateral vaginal wall)
Maternal Physiology
EMBRYOLOGY OF THE GONADS UTERUS
• 4 weeks: gonads derive from coelomic epithelium • Relatively thin-walled muscular organ of sufficient
covering the medial and ventral surface of the capacity to accommodate the fetus, placenta and
nephrogenic cord (8th thoracic and 4th lumbar amnionic fluid
segments) • Total volume: 5L (but may be 20L or more)
• Coelomic epithelium thickens to form the genital ridge / • 1100grams in pregnancy
gonadal ridge • 70 grams in nonpregnant state
• 6 weeks: primordial germ cells have migrated from the • In the beginning the corpus becomes markedly thicker
yolk sac to enter the genital ridge mesenchyme but begins to thin gradually → by term: 1-2cm thick
• 7 weeks: sexes can be distinguished • Hypertrophy is stimulated by the action of estrogen
o Testes by their well-defined radiating testis • After 12 weeks → uterine size increases due to the
cords pressure exerted by the expanding products of
o Testis cords → seminiferous tubules and rete conception
testis Myocyte Arrangement:
o Rete testis establishes connection with small • Outer layer: hoodlike layer which arches over the
tubes arising off the mesonephric duct fundus and extends in the various ligaments
• Middle layer: dense network of muscle fibers
HOMOLOGUES perforated in all directions by blood vessels
Indifferent Structure Female Male • Internal layer: sphincter like fibers around the fallopian
Genital ridge Ovary Testis tube orifices and internal cervical os
Primordial germ cells Ova Spermatozoa Uterine size, shape and position:
Sex cords Granulosa cells Seminiferous • Increases more rapidly in length than in width
tubules, Sertoli • Dextrorotation is caused by the rectosigmoid on the left
cells side of the pelvis
Gubernaculum Uteroovarian Gubernaculum • As the uterus rises → tension is exerted on the broad
and round testis and round ligaments
ligaments Uteroplacental blood flow:
Mesonephric ducts Gartner duct Epididymis, • Placental perfusion is dependent on total uterine blood
ductus deferens, flow
ejaculatory duct Uteroplacental blood flow regulation:
Paramesonephric ducts Uterus, fallopian Prostatic utricle, • Maternal-placental blood flow progressively increases
tubes, upper appendix of testis during testation principally by means of vasodilation
vagina • Uterine artery doubled by 20 weeks
Urogenital sinus Bladder, urethra, Bladder, urethra, • Slight diameter increases in the uterine artery produces
vagina, prostatic utricle, a tremendous blood flow capacity increase
paraurethral prostate glands, • Spiral arteries directly supply the placenta
glands, greater bulbourethral • Vasodilation is a consequence of estrogen stimulation
(Bartholin) and glands
lesser vestibular CERVIX
glands • As early as 1 month after conception: increased
Genital tubercle Clitoris Glans penis vascularity and edema of the entire cervix +
Urogenital folds Labia minora Floor of penile hypertrophy and hyperplasia of cervical glands = cervix
urethra begins to undergo pronounced softening and cyanosis
Labioscrotal swellings Labia majora Scrotum • Major component: connective tissue
• Ripening involves connective tissue remodeling that
• In males: fetal testis secretes Mullerian inhibiting decreases collagen and proteoglycan concentrations
substance (MIS) or anti-Mullerian hormone (AMH) and increases water content
which acts as a paracrine factor to cause Mullerian duct • Cervical glands undergo marked proliferation
regression • Eversion due to normal pregnancy induced changes of
• AMH is produced by the Sertoli cells the proliferating columnar endocervical glands
o Secreted as early as 7 weeks and Mullerian • As a result of progesterone → beading
duct regression is completed by 9-10 weeks • Amniotic fluid leakage → ferning
• Changes in pregnancy is associated with both
endocervical gland hyperplasia and hypersecretory
appearance → Arias-Stella reaction

OVARIES
8
 • Corpus luteum functions maximally during the first 6-7
weeks of pregnancy (4-5 weeks post ovulation) → little
progesterone production
o Surgical removal of the corpus luteum before
7 weeks = rapid fall in maternal serum
progesterone → spontaneous abortion
• Relaxin
o Secreted by the corpus luteum
o Remodels the reproductive tract connective
tissue to accommodate parturition
• Theca lutein cysts
o From exaggerated physiological follicle
stimulation “hyperreaction luteinalis”
o Serum levels of hCG elevate
VAGINA AND PERINEUM
• Bartholin duct cysts are common
• Increased vascularity → Chadwick sign
• Increased production of lactic acid from glycogen in the
vaginal epithelium by the action of Lactobacillus
acidophilus
METABOLIC CHANGES
• By the 3rd trimester maternal basal metabolic rate is
increased by 20% (additional 10% if twin pregnancy)
• 77,000 kcal
o 85kcal – 1st trimester
o 285kcal – 2nd trimester
o 475kcal – 3rd trimester
• Average weight gain during pregnancy: 12.5kg or
27.5lbs
• Water metabolism
o Increased water retention is a normal
physiological alteration of pregnancy
o Fall in plasma osmolality by 10 mOsm/kg →
resetting of osmotic thresholds for thirst and
vasopressin
o At term, water content of fetus, placenta and
AF: 3.5L, another 3L accumulates from
increases in maternal blood volume and in the
size of the uterus and breasts
o Edema is caused by increased venous
pressure below the level of the uterus
• Protein metabolism
o Amino acid concentrations are higher in the
fetal than in the maternal compartment
• Carbohydrate metabolism
HEMATOLOGIC CHANGES
o Normal pregnancy is characterized by mild
BLOOD VOLUME
fasting hypoglycemia, postprandial
hyperglycemia and hyperinsulinemia
o In short, there is an increased basal level of
plasma insulin
o After a high glucose meal → prolonged
hyperglycemia and hyperinsulinemia
o Pregnancy induced state of peripheral insulin
resistance → purpose is to ensure a sustained
postprandial supply of glucose to the fetus
• Fat metabolism
o 1st and 2nd trimester: maternal fat
accumulation
o 3rd trimester: fat storage declines as a
consequence of increased lipolytic activity
o Leptin:
▪ Nonpregnant: secreted by adipose
tissue
▪ Key role in body fat and energy
expenditure regulation
▪ Associated with anovulation and
infertility
▪ Peak during the 2nd trimester and
plateau until term 2-4x higher
▪ Associated with preeclampsia and
GDM
o Ghrelin
▪ Increase and peak at midpregnancy
and decrease until term
▪ Present in the placenta and likely
has a role in fetal growth and cell
proliferation
o Visfatin
▪ Growth factor for B lymphocytes
▪ Mainly produced within adipose
tissue
▪ Elevated levels of visfatin and leptin
impair uterine contractility
• Electrolyte and mineral metabolism
o Nearly 1000 mEq of Na and 300 mEq of K are
retained
o Total serum ca decline
▪ Fetal skeleton accretes approx. 30g
of calcium by term 80% of which is
deposited during the 3rd trimester)
o Serum Mg levels also decline
▪ Pregnancy is a state of extracellular
magnesium depletion
o Iodine requirements increase during normal
pregnancy
▪ Maternal T4 production increases to
maintain maternal euthyroidism
and to transfer thyroid hormone to
the fetus early in gestation before
the fetal thyroid is functioning
▪ Fetal thyroid hormone production
increases during the 2nd half of
pregnancy → increased maternal
iodine requirements (iodide readily
crosses the placenta)
▪ Primary route of iodine excretion is
through the kidney
• Hypervolemia with normal pregnancy: 40-45% above
the nonpregnant blood volume after 32-34 weeks AOG
• Pregnancy induced hypervolemia has several important
functions:
o Meets the metabolic demands of the enlarged
uterus and its greatly hypertrophied vascular
system
o Provides abundant nutrients and elements to
support the rapidly growing placenta and
fetus
o Protects mother and fetus against deleterious
effects of impaired venous return in the
supine and erect position
9
 o Safeguards the mother against adverse
effects of parturition associated blood loss
• Increases during the 1st trimester
• 12 weeks = plasma volume expands by 15%
• Results from an increase in both plasma and
erythrocytes
• Blood volume grows most rapidly during midtrimester
and rises as a much slower rate during the 3rd trimester
IRON METABOLISM
• total iron content of a normal adult woman ranges from
2-2.5g ~ 300mg
• Iron requirements:
o Of the 1000mg of iron required for normal
pregnancy, 300mg are actively transferred to
the fetus and placenta
o 200mg lost through normal excretion routes
o 500mg to increase the total circulating
erythrocyte volume
o 1ml of erythrocyte = 1.1mg of iron
IMMUNOLOGICAL FUNCTIONS
• One immune adaptation that promotes tolerance and
protection at the maternal-fetal interface involves the
expression of special major histocompatibility complex
(MHC) molecules on the trophoblast
• Trophoblast cells express a form of MCH that does not
vary between individuals. This “nonclassic MHC” is
known as human leukocytes antigen class Ib (HLA-E,
HLA-F, HLA-G)
o Recognition of these HLA class Ib proteins by
NK cells residing in the decidual inhibits their
activity and promotes immune quiescence
• Proinflammatory and anti-inflammatory condition
• Early pregnancy: proinflammatory
o During implantation and placentation, the
blastocyst must break through the uterine
cavity epithelial lining to invade the
endometrial tissue → trophoblast must then
replace the endothelium and vascular smooth
muscle to secrete an adequate blood supply
for the placenta = “battleground” of invading
cells, dying cells and repairing cells THUS an
inflammatory environment is required to
secure cellular debris removal and adequate
repair of the uterine epithelium
• Mid pregnancy: anti-inflammatory
o Period of rapid fetal growth and development
→ anti-inflammatory state
• Latter pregnancy: influx of immune cells into the
myometrium to promote recrudescence of an
inflammatory process
• Suppression of Th1 and cytotoxic T cells → decreased
secretion of IL-2, interferon and tumor necrosis factor
→ more prone to developing RA, multiple sclerosis,
hashimoto thyroiditis (TH1 mediated disease)
LEUKOCYTES
• Higher than prepregnant values
• T lymphocytes increase (B lymphocytes remain the
same)
• As high as 15,000 and as high as 25,000 when giving
birth
COAGULATION AND FIBRINOLYSIS
• Increased concentration of all clotting factors EXCEPT
11 and 13
• Fibrinolytic activity is reduced in normal pregnancy →
coagulation is impaired
PLATELETS
• Decreased slightly in pregnancy due to hemodilutional
effects
SPLEEN
• Enlarges by up to 50% in the third trimester
CARDIOVASCULAR SYSTEM
• Changes become apparent during the first 8 weeks of
pregnancy
• CO is increased as early as the 5th week
• Resting pulse rate rises approximately 10bpm during
pregnancy
• HR increases significantly between 12-16 weeks and
between 32-36 weeks
• Between weeks 10 and 20 plasma volume expansion
begins and preload rises → larger left atrial volumes
and ejection fractions
HEART
• Displaced to the left and upward due to the rise of the
diaphragm
• Exaggerated splitting of the first heart sound and
increased loudness of both components
• No definite change in the aortic and pulmonary
elements of the second sound
• Loud, easily heard third sound
• Ventricular function is normal
CARDIAC OUTPUT
• Mean arterial pressure and vascular resistance decrease
• Blood volume, BMR increase
• Cardiac output increases 1.2L/min (almost 20%) when a
woman was moved from her back onto her left side at
26-30 weeks and at 32-34 weeks by 10%
HEMODYNAMIC FUNCTION IN LATE PREGNANCY
• Late pregnancy was associated with the expected
increases in heart rate, stroke volume and cardiac
output
• Systemic vascular and pulmonary vascular resistance
both dropped
• Pulmonary capillary wedge pressure and CVP did not
change
• CO rises
• Left ventricular function remains the same
CIRCULATION AND BLOOD PRESSURE
• Tendency toward blood stagnation in the lower
extremities during latter pregnancy is attributable to
occlusion of the pelvic veins and IVC by the enlarged
uterus
• Brachial artery pressure when sitting is lower than that
when in the lateral recumbent position
• SBP is lower in the lateral positions compared with
sitting or supine
• Diastolic pressure decreases more than systolic
• Pregnancy confers a favorable effect on maternal
cardiovascular remodeling and may explain why the risk
of preeclampsia is reduced in subsequent pregnancies
10
RENIN, ANGIOTENSIN II AND PLASMA VOLUME
• Renin is produced by both the maternal kidney and
placenta
• Greater amounts of renin substrate (angiotensinogen)
are produced by both maternal and fetal liver
ENDOTHELIN
• Potent vasoconstrictor produced in endothelial and
vascular smooth muscle cells and regulates local
vasomotor tone
• Production is stimulated by angiotensin II, arginine
vasopressin and thrombin
RESPIRATORY TRACT
• Diaphragm rises about 4cm during pregnancy
• Transverse diameter of the thoracic cage lengthens
approximately 2cm
• Thoracic circumference increases by 6cm
• FRC decreases by 20-30% (400-700ml)
o Components:
▪ ERV drops 15-20%
▪ RV decreases 20-25%
o Due to diaphragm elevation
• Inspiratory capacity (max volume that can be inhaled
from FRC) rises by 5-10% (200-350ml)
• TLC (FRc + IC) is unchanged or decreases by <5% at term
• Lung compliance is unaffected
• Airway conductance is increased
• Total pulmonary resistance reduced
URINARY SYSTEM
KIDNEY
• Increases approximately 1.5cm
• GFR and renal plasma flow increase early in pregnancy
GASTROINTESTINAL TRACT
• Gastric emptying time appears unchanged
LIVER
• Serum albumin concentration decreases during
pregnancy
GALLBLADDER
• Gallbladder contractility is reduced → increased
residual volume
• Progesterone impairs gallbladder contraction by
inhibiting cholecystokinin-mediated smooth muscle
stimulation
ENDOCRINE SYSTEM
• By the 17th week the placenta is the principal source of
growth hormone secretion
• Placental growth hormone is secreted by a
syncytiotrophoblast in a nonpulsatile fashion
• Principal function of maternal prolactin is to ensure
lactation
• Early in pregnancy → prolactin acts to initiate DNA
synthesis and mitosis of glandular epithelial cells and
presecretory alveolar cells of the breast
• At 20-26 weeks: 10,000ng/ml (high concentrations) →
decrease at 34 weeks
THYROID GLAND
• Increase production of thyroid hormones by 40-100%
• Thyroid gland undergoes moderate enlargement during
pregnancy caused by glandular hyperplasia and
increased vascularity
• The rise in Free serum T4 levels rise slightly and peak
along with hCG levels at 18 weeks then it plateaus
• At birth approximately 30% of the T4 in umbilical cord
blood is of maternal origin
• The alpha subunits of the 2 glycoproteins (TSH and hCG)
are identical whereas the beta subunits differ in their
amino acid sequence
ADRENAL GLANDS
• Cortisol
o Serum concentration rises but most of it is
bound by transcortin
• Androgens
o Both androgens (androstenedione and
testosterone) are converted to estradiol in
the placenta which increases their clearance
rates
• Aldosterone
o As early as 15 weeks, the maternal adrenal
glands secrete increased amounts
o By the 3rd trimester, approx. 1mg/d is
released
o If Na is restricted = aldosterone is further
elevated
CENTRAL NERVOUS SYSTEM
• Eyes: IOP drops due to a greater vitreous outflow
Corneal sensitivity is decreased
CHAPTER 5
Menstrual Cycle, Placental Development
THE OVARIAN CYCLE
• Follicular or Preovulatory Ovarian Phase
o During each ovarian cycle a group of antral
follicles (known as a cohort) begins a phase of
semi synchronous growth based on their
maturation state during the FSH rise in the
late luteal phase
o FSH rise leading to follicle development is
called the selection window
o Estrogen levels rise
o Granulosa cells: exclusive site of FSH receptor
expression → FSH induces aromatase and
expansion of the antrum of growing follicles
o After the appearance of LH receptors, the
preovulatory granulosa cells begin to secrete
small quantities of progesterone
• Ovulation
o Increasing estrogen secretion by the
preovulatory follicles (34-36 hours before
ovum release) → gonadotropin surge
o LH secretion peaks 10 to 12 hours before
ovulation and stimulates resumption of
meiosis in the ovum and release of the first
polar body
• Luteal or Postovulatory Ovarian Phase
11
 o After ovulation → corpus luteum develops
from the dominant or Graafian follicle
(Luteinization)
o LH is the primary luteotropic factor
responsible for corpus luteal maintenance
o Ovarian progesterone production peaks at 25-
50mg/day during the mid-luteal phase → with
pregnancy: corpus luteum continues
progesterone production in response to
embryonic hCG
o Corpus luteum will rapidly regress 9-11 days
after ovulation via apoptosis
• MOST POTENT NATURALLY OCCURING ESTROGEN: 17B-
ESTRADIOL → secreted by granulosa cells of the
dominant follicle and luteinized granulosa cells of the
corpus luteum
• Estrogen is the essential hormonal signal on which most
events in the normal mens cycle depend
THE ENDOMETRIAL CYCLE
Proliferative or Preovulatory Endometrial Phase
• Epithelial – glandular cells
• Stromal – mesenchymal cells
• Follicular phase estradiol is the most important factor in
endometrial recovery following menstruation
• Late proliferative phase – endometrium thickens from
both glandular hyperplasia and increased stromal
ground substance
• At midcycle (as ovulation nears) → glandular epithelium
becomes taller and pseudostratified
Secretory or Postovulatory Endometrial Phase
• First histologic sign of ovulation: glycogen accumulates
in the basal portion of glandular epithelium creating
subnuclear vacuoles and pseudo stratification
o Result of direct progesterone action through
receptors expressed in glandular cells
• Day 18: vacuoles move to the apical portion of the
secretory nonciliated cells
• Day 19: cells begin to secrete glycoprotein and
mucopolysaccharide contents into the lumen
o Glandular cell mitosis ceases due to the rising
progesterone levels which antagonize mitotic
effects of estrogen
• Days 21-24: stroma become edematous
• Days 22-25: stromal cells surrounding the spiral
arterioles begin to enlarge and stromal mitosis becomes
apparent
o Striking changes associated with predecidual
transportation of the upper 2/3 of the
functionalis layer
o Glands exhibit extensive coiling and luminal
secretions become visible
• Days 23-28: predecidual cells which surround spiral
arterioles
• Epithelial surface cells show decreased microvilli and
cilia but appearance of luminal protrusions on the
apical cell surface → important in preparation for
blastocyst implantation
• Uterine vessels → arcuate → radial → spiral or coiled
arteries
o During endometrial growth, spiral arteries
lengthen at a rate greater than the rate of
endometrial tissue thickening
o Obliging even greater coiling of the already
spiraling vessels
o Spiral artery development reflects marked
induction of angiogenesis consisting of
widespread vessel sprouting and extension
Menstruation
• If luteal progesterone production decreases with
luteolysis events leading to menses are initiated
• Stromal infiltration by neutrophils →
pseudoinflammatory appearance to the tissue
• Endometrial and epithelial cells produce IL-8
(chemotactic activating factor for neutrophils)
• Leukocyte infiltration is a key to both endometrial
extracellular matrix breakdown and repair of the
functionalis layer
Anatomical Events During Menstruation:
• Marked changes in endometrial blood flow essential for
menses → endometrial regression → spiral artery
coiling becomes sufficiently severe that resistance to
blood flow increases → endometrial hypoxia →
ischemia and tissue degeneration
Prostaglandins and Menses
• Progesterone withdrawal increases expression of COX2
to synthesize prostaglandins
• Withdrawal also decreases expression of 15-
hydroxyprostaglandin dehydrogenase (PGDH) which
degrades prostaglandins → increased prostaglandin
production by endometrial stromal cells and increased
prostaglandin-receptor density on blood vessels and
surrounding cells
• Large amounts of prostaglandins are present in
menstrual blood
• Myometrial contractions and uterine ischemia are
mediated by PGF2a induced spiral artery
vasoconstriction that causes the uppermost
endometrial zones to become hypoxic → angiogenesis
→ vascular permeability factors (VEGF)
Activation of Lytic Mechanisms
• Following vasoconstriction and endometrial cytokine
changes → protease activation within stromal cells and
leukocyte invasion is required to degrade the
endometrial interstitial matrix
12
 • Matrix metallopreteases MMP1 and MMP3 are
released from stromal cells and may activate MMP8
and MMP9
Origin of Menstrual Blood
• More arterial than venous
• Follows rupture of a spiral arteriole and consequent
hematoma formation
THE DECIDUA
• Specialized highly modified endometrium of pregnancy
• Essential for hemochorial placentation (one in which
maternal blood contacts trophoblast)
• Decidualization – transformation of secretory
endometrium to decidua → dependent on estrogen
and progesterone
Decidual structure
• Basalis: directly beneath blastocyst implantation
modified by trophoblast invasion
o Contributes to formation of the placental
basal plate
o Spongy zone of decidua basalis contains
mainly of arteries and widely dilated veins →
by term: glands have virtually disappeared
o Invaded by many interstitial trophoblast cells
and trophoblastic giant cells
• Capsularis: overlies the enlarging blastocyst and initially
separates the conceptus from the rest of the uterine
cavity
o Most prominent during the second month of
pregnancy and consists of decidual cells
covered by a single layer of flattened
epithelial cells
• Parietalis: remainder of the uterus lining
• In early pregnancy: space between the decidual
capsularis and parietalis becomes the gestational sac
• By 14 to 16 weeks: expanding sac has enlarged to
completely fill the uterine cavity
DECIDUAL REACTION
• Completed with blastocyst implantation
• Endometrial cells enlarge to form polygonal and round
decidual cells
• Nuclei becomes round and vesicular
• Cytoplasm becomes clear
• Human decidual cells build walls around themselves
and around the fetus
DECIDUAL BLOOD SUPPLY
• As a consequence of implantation → blood supply to
the decidual capsularis is lost as the embryo/fetus
grows
• Spiral arterioles and arteries are invaded by
cytotrophoblasts → vessel walls in the basalis are
destroyed
DECIDUAL HISTOLOGY
• Early in pregnancy: zona spongiosa of the decidua
consists of large distended glands exhibiting marked
hyperplasia
• At first lined by cylindrical uterine epithelium
(contributes to blastocyst nourishment) → as
pregnancy progresses → epithelium becomes cuboidal
or flattened → degenerates and slough to a greater
extent → later on in pregnancy the elements largely
disappear
• Nitabuch layer: zone of fibrinoid degeneration in which
invading trophoblasts meet the decidua basalis
o If the decidua is defective (placenta accrete)
→ the nitabuch layer is usually absent
DECIDUAL PROLACTIN
• Decidua is the source of prolactin that is present in
enormous amounts in amnionic fluid → enters
amnionic fluid and little enters maternal blood
• Human placental lactogen (hPL) produced by
syncytiotrophoblast
IMPLANTATION AND EARLY TROPHOBLAST FORMATION
FERTILIZATION AND IMPLANTATION
• Ovulation → secondary oocyte and adhered cells of the
cumulus-oocyte complex are freed from the ovary
THE ZYGOTE
• A diploid cell with 46 chromosomes
• Undergoes cleavage and zygote cells produced by this
division are called blastomeres
• Blastomeres and polar body continue to be surrounded
by the zona pellucida → undergoes slow cleavage for 3
days while still within the fallopian tube
• As the blastomeres continue to divide → morula is
produced → enters the uterine cavity about 3 days
after fertilization
THE BLASTOCYST
• As early as 4-5 days after fertilization the 58-cell
blastula differentiates into 5 embryo producing cells →
the inner cell mass and 53 cells destined to form the
trophoblast
13
 • Blastocyst implantation
o 6-7 days after fertilization, the embryo
implants the uterine wall
o Apposition: initial contact of the blastocyst to
the uterine wall
▪ The blastocyst loosely adheres to
the endometrial epithelium by
apposition
▪ Occurs on the upper posterior
uterine wall
o Adhesion: increased physical contact between
the blastocyst and uterine epithelium
o Invasion: penetration and invasion of
syncytiotrophoblast and cytotrophoblasts into
the endometrium, inner third of the
myometrium and uterine vasculature
• Adherence is mediated by cell-surface receptors at the
implantation site that interact with blastocyst receptors
THE TROPHOBLAST
• The most variable structure, function and
developmental pattern of all placental components
• By the 8th day post fertilization, the trophoblast
differentiates into the syncytiotrophoblast and an inner
layer of primitive mononuclear cells – cytotrophoblasts
(germinal cells from the syncytium)
• Cytotrophoblast has a well demarcated cell border, a
single nucleus and an ability to undergo DNA synthesis
and mitosis – has an amorphous cytoplasm without cell
borders, nuclei that are multiple and diverse in size and
shape → aids in transport
• After implantation → 2 main pathways → villous ex
travillous trophoblast
o Villous trophoblast → chorionic villi (for
transport of oxygen, nutrients and other
compounds between the fetus and the
mother)
o Extravillous trophoblasts: migrate into the
decidua and myometrium and also penetrate
maternal vasculature thus coming into
contact with various maternal cell types
▪ Interstitial trophoblasts
• Invade the decidua and
penetrate the
myometrium to form
placental bed giant cells
▪ Endovascular trophoblasts
• Penetrate the spiral artery
lumens
EARLY TROPHOBLAST INVASION
• By the 10th day the blastocyst becomes totally encased
within the endometrium
• Embryonic mesenchyme first appears as isolated cells
within the blastocyst cavity
Lacunae Formation within the Syncytiotrophoblast
• Beginning approximately 12 days after conception the
syncytiotrophoblast is permeated by a system of
intercommunicating channels called trophoblastic
lacunae
PLACENTAL ORGANIZATION
Chorionic villi
• 12th day after fertilization → mesenchymal cords
derived from extraembryonic mesoderm invade the
solid trophoblast columns to form the secondary villi
• 17th day: fetal blood vessels are functional, and a
placental circulation is established
•
PLACENTA AND CHORION DEVELOPMENT
CHORION AND DECIDUA DEVELOPMENT
• As the blastocyst with its surrounding trophoblasts
grows and expands into the decidua one pole faces the
endometrial cavity, the opposite pole will form the
placenta from villous trophoblasts and anchoring
cytotrophoblasts
• Chorionic villi in contact with the decidua basalis
proliferate to form the chorion frondosum (leafy
chorion – the fetal component of the placenta)
• The dNK cells (decidual natural killer cells) prevent the
body from destroying the fetus because they lack
cytotoxic functions and are able to dampen
inflammatory cells
o Produce IL8 and interferon inducible protein-
10 which bind to receptors on invasive
trophoblast cells to promote their decidual
invasion toward the spiral arteries
o Also produce proangiogenic factors (VEGF and
placental growth factor) which promote
vascular growth in the decidua
• Low estradiol levels in the first trimester are critical for
trophoblast invasion and remodeling of the spiral
arteries
INVASION OF SPIRAL ARTERIES
• Fibrinoid material replaces smooth muscle and
connective tissue of the vessel media
• Spiral arteries later regenerate endothelium
• 2 waves:
o First wave: before 12 weeks postfertilization
→ invasion and modification of spiral arteries
up to the border between the decidua and
myometrium
o Second wave: 12-16 weeks → invasion of the
intramyometrial segments of spiral arteries
PLACENTAL GROWTH AND MATURATION
Placental Growth:
• First trimester: placental growth is more rapid than that
of the fetus
• 17 postmenstrual weeks: placental and fetal weights
are approximately equal
• By term: placental weight is approximately 1/6 of the
fetal weight
Placental Maturation
• Infiltration of Hoffbauer cells (fetal macrophages)
o Histochemical: intracytoplasmic lipid and by
phenotypic markers specific for macrophages
o Protects maternal-fetal interface
o These macrophages are phagocytic, have an
immunosuppressive phenotype, can produce
various cytokines, and are capable of
paracrine regulation of trophoblast functions
Maternal Circulation
• Spiral arteries are perpendicular to the uterine wall
• Veins are parallel to the uterine wall
14
 • This arrangement aids closure of veins during a uterine
contraction and prevents the exit of maternal blood
from the intervillous space
• 120 spiral arteries entries into the intervillous space at
term
Breaks in the Placental “Barrier”
• Erythrocyte D-antigen alloimmunization →
erythroblastosis fetalis
Immunological considerations of the fetal-maternal interface
• Class I antigens in Extravillous cytotrophoblasts are
accounted by the expression of HLA-C and nonclassic
class Ib molecules of HLA-E, HLA-G
• HLA-G: expressed only in humans with expression
restricted to Extravillous cytotrophoblasts
o Identified only in Extravillous
cytotrophoblasts in the decidua basalis
o Soluble major isoform HLAG2 has increased
levels
▪ Embryos from IVF must express this
in order to implant
THE AMNION
• Provides all tensile strength of the fetal membranes
• Inner surface (bathed in AF): cuboidal epithelium
• Outermost: acellular zona spongiosa
• Lacks smooth muscle cells, nerves, lymphatics and
blood vessels
AMNION DEVELOPMENT
• First identifiable during the 7th or 8th day of embryo
development
AMNION TENSILE STRENGTH
• Collagen I is the major interstitial collagen in tissues
characterized by great tensile strength
• Regulated in part by fibrillary collagen interacting with
proteoglycans such as decorin which promote tissue
strength
• At time of labor → decline in decorin, increase in
hyaluronan → loss of tensile strength
HCG
• Glycoprotein with biological activity similar to LH
• Produced by the placenta, low levels are synthesized in
the fetal kidney
• The detection of hCG in blood or urine almost always
indicates pregnancy
CHEMICAL CHARACTERISTICS
• Because of its high carbohydrate component, it protects
the molecule from catabolism
• Structurally related to the three other glycoproteins –
LH, FSH, TSH → all four glycoproteins share a common
alpha subunit
BIOSYNTHESIS
• Single gene located on chromosome 6 encodes the
alpha subunit
• 7 genes on chromosome 19 encode for the beta subunit
• Before 5 weeks: hCG is expressed in both
syncytiotrophoblast and cytotrophoblast → when
maternal serum levels peak: hCG is produced almost
solely in the syncytiotrophoblast
• Combined hCG molecule is detectable in plasma 7-9
days after the midcycle surge of LH that precedes
ovulation
• hCG only enters maternal blood at the time of
blastocyst implantation
• Doubles every 2 days in the 1st trimester
• Peak maternal plasma levels reach 100,000 mIU/ml
between the 60th and 80th days after menses
• 10-12 weeks: plasma levels begin to decline, and a nadir
is reached by approximately 16 weeks
• 30% excreted thru urine, and the rest is metabolized by
the liver
BIOLOGIC FUNCTIONS
• Rescue and maintenance of the corpus luteum function
→ continued progesterone production
o Progesterone luteal synthesis begins to
decline at about 6 weeks despite continued
and increasing hCG production
• Stimulation of fetal testicular testosterone secretion
o At a critical time in male sexual
differentiation, hCG enters fetal plasma from
the syncytiotrophoblast → fetus: it acts as an
LH surrogate to stimulate Leydig cell
replication and testosterone synthesis to
promote male sexual differentiation
• Stimulation of the maternal thyroid gland
• Promotion of relaxin secretion by the corpus luteum
HPL
• hPL secretion rate is proportional to placental mass
• Metabolic Actions
o Promotes maternal lipolysis with increased
circulating free fatty acid levels
o Serves an important function in fetal
vasculature formation
OTHER PLACENTAL PROTEIN HORMONES
RELAXIN
• Similar to insulin and insulin-like growth factor
• Act on the myometrium to promote relaxation and the
quiescence
• Enhances glomerular filtration rate
PLACENTAL PROGESTERONE PRODUCTION
• At 6-7 weeks, little progesterone is produced in the
ovary → surgical removal of the corpus luteum or even
bilateral oophorectomy during the 7th-10th week of
pregnancy does not decrease excretion rates of urinary
pregnanediol, the principal urinary metabolite of
progesterone
• Before this time, corpus luteum removal will result in
spontaneous abortion
• After 8 weeks, the placenta assumes progesterone
secretion → gradual increase in maternal serum levels
throughout pregnancy
• During the first 2-4 weeks of pregnancy, rising hCG
levels maintain production of estradiol in the maternal
corpus luteum
15
PLACENTAL ESTROGEN BIOSYNTHESIS
• Crucial enzyme necessary for sex steroid synthesis –
steroid 17a-hydroxylase (CYP17)
• Dehydroepiandrosterone (DHEA) and its sulfate (DHEA-
S) are C19 steroids → can serve as estrogen receptors
• The fetal adrenal glands are quantitatively the most
important source of placental estrogen precursors in
human pregnancy
DIRECTIONAL SECRETION OF STEROIDS FROM
SYNCYTIOTROPHOBLAST
• More than 90% of estradiol and estriol formed in
syncytiotrophoblast enters the maternal plasma
• 85% or more of placental progesterone enters the
maternal plasma with little maternal progesterone
crossing the placenta to the fetus
PLACENTAL ESTRIOL SYNTHESIS
• Estradiol is the primary placental estrogen secretory
product at term
• Near term, the fetus is the source of 90% of placental
estriol and esterol precursor in normal human
pregnancy
FETAL ADRENAL STEROID PRECURSOR
• Precursor: cholesterol
• Fetal adrenal glands synthesize cholesterol from
acetate
• Among the lipoproteins LDL was most effective
FETAL CONDITIONS THAT AFFECT ESTROGEN PRODUCTION
• Fetal demise:
o Reduction in urinary estrogen levels
• Fetal anencephaly
o Absence of the adrenal cortex fetal zone
o Placental estrogen formation rate is limited
because of diminished availability of C19
steroid precursors
• Fetal adrenal hypoplasia
o Estrogen production is limited
• Fetal placental sulfatase deficiency
o X linked disorder
o All affected fetuses are male
o Delayed onset of labor
• Fetal placental aromatase deficiency
o Normally: fetal adrenal DHEA-S is converted in
the placenta to androstenedione BUT in cases
of placental aromatase deficiency,
androstenedione cannot be converted to
estradiol
• Trisomy 21
o Serum unconjugated estriol levels were low in
women with Down syndrome
o Due to inadequate formation of C19 steroids
in the adrenal glands
• Deficiency in fetal LDL cholesterol biosynthesis
o Absence of LDL in the maternal serum
restricted progesterone formation in both the
corpus luteum and placenta
• Fetal erythroblastosis
o Maternal plasma estrogen levels are elevated
likely from an increased placental mass from
hypertrophy
MATERNAL CONDITIONS THAT AFFECT PLACENTAL ESTROGEN
PRODUCTION
• Glucocorticoid treatment
o Causes a striking reduction in placental
estrogen formation
o Inhibit ACTH secretion from the maternal and
fetal pituitary glands → decreased maternal
and fetal adrenal secretion of the placental
estrogen precursor DHEA-S
• Maternal adrenal dysfunction
o In pregnant women with Addison disease
• Maternal ovarian androgen producing tumors
o All androstenedione entering the intervillous
space is taken up by syncytiotrophoblast and
converted to estradiol
o Female fetus is rarely virilized if there is a
maternal androgen secreting ovarian tumor
• Gestational trophoblastic disease
o With a choriocarcinoma, there is no fetal
adrenal source of C19 steroid precursor fort
trophoblast estrogen biosynthesis
CHAPTER 6
Placental Abnormalities
MATERNAL INDICATIONS FOR PATHOLOGICAL EXAMINATION
• Abruption
• Antepartum infection with fetal risks
• Anti-CDE alloimmunization
• Cesarean hysterectomy
• Oligohydramnios or hydramnios
• Peripartum fever or infection
• Preterm delivery
• Post term delivery
• Severe trauma
• Suspected placental injury
• Systemic disorders with known effects
• Thick or viscid meconium
• Unexplained late pregnancy bleeding
• Unexplained or recurrent pregnancy complications
FETAL AND NEONATAL INDICATIONS
• Admission to an acute care nursery
• Birth weight ≤ 10th or ≥ 95th percentile
• Fetal anemia
• Fetal or neonatal compromise
• Neonatal seizures
• Hydrops fetalis
• Infection or sepsis
• Major anomalies or abnormal karyotype
• Multifetal gestation
• Stillbirth or neonatal death
• Vanishing twin beyond the first trimester
PLACENTAL INDICATIONS
• Gross lesions
• Marginal or velamentous cord insertion
• Markedly abnormal placental shape or size
16
 • Markedly adhered placenta ▪Marginal hematoma: chorion and
• Term cord < 32 cm or > 100 cm decidua at the placental periphery
• Umbilical cord lesions (aka subchorionic hemorrhage)
NORMAL PLACENTA ▪ Subchorial – breus mole: along the
• At term: 470grams, 22cm diameter, central thickness of roof of the intervillous space and
2.5cm beneath the chorionic plate
• Maternal surface – basal plate divided into cotyledons ▪ Subamnionic: fetal vessel origin
• Fetal surface – chorionic plate where the umbilical cord found beneath the amnion but
inserts above the chorionic plate
o Covered by a thin amnion which can be easily ▪ Sonographically: crescent shaped
peeled away from a postdelivery specimen fluid collection hyperechoic to
• Sonographically: normal placenta is homogenous, 2- isoechoic in the first week after
4cm thick against the myometrium hemorrhage → hypoechoic 1-2
• Retroplacental space 1-2cm weeks and anechoic after 2 weeks
ABNORMALITIES OF THE PLACENTA • Disturbed fetal blood flow through the villi
Shape and Size o Fetal thrombotic vasculopathy: deoxygenated
• Multilobate: three or more equally sized lobes fetal blood flows from the 2 umbilical arteries
• Placenta membranacea: all or nearly all of the into arteries within the chorionic plate that
membranes are covered with villi divide and send branches out across the
o Ring shaped placenta placental surface → will eventually obstruct
fetal blood flow
• Placenta fenestrata: central portion of a placental disc is
o Subamnionic hematoma
missing
PLACENTAL CALFICIFACTION
• Placentomegaly: thicker than 40mm
• Calcium salts in the placenta – most common on the
basal plate
Extra chorial placentation • Associated with advancing gestation, nulliparity,
smoking, higher socioeconomic status and increasing
• Most pregnancies have normal outcomes
maternal serum calcium levels
• Circumvallate: associated with increased risk for
antepartum bleeding and preterm birth
PLACENTAL TUMORS
Placental accreta, increta, percreta
• Gestational trophoblastic disease
• Chorioangioma: benign
o Have components similar to blood vessels and
stroma of the chorionic villus
o 1% incidence
o if larger than 5cm → may be associated with
significant arteriovenous shunting → fetal
CIRCULATORY DISTURBANCES anemia and hydrops
• Disrupted maternal blood flow • Tumors metastatic to the placenta
o Subchorionic fibrin deposition: caused by o Malignant tumors rarely metastasize to the
slowing of maternal blood flow within the placenta
intervillous space with subsequent fibrin o Melanomas, leukemias, lymphomas, breast
deposition → blood stasis occurs in the cancer
subchorionic area
o Perivillous fibrin deposition: fibrin deposition AMNIOCHORION
that can lead to diminished villous CHORIOAMNIONITIS
oxygenation and syncytiotrophoblastic • Bacteria ascend after prolonged ROM
necrosis • Inflammation of the chorionic plate and the UC
o Maternal floor infarction: associated with (funisitis) may follow
miscarriage, fetal growth restriction, preterm
delivery and stillbirths; associated with lupus OTHER MEMBRANE ABNORMALITIES
Amnion Numerous
anticoagulant
nodosum small (<1cm),
o Intervillous thrombus: collection of light tan
coagulated maternal blood normally found in nodules on
the intervillous space mixed with fetal blood the amnion
from a break in a villus overlying the
o Infarction: benign when thin, when thick and chorionic
centrally located, they may be associated with plate
preec or lupus
o Hematoma:
▪ Retroplacental: placenta and its
adjacent decidua
17
Amnionic • Amnion production
band bands GnRH Hypothalamus - Regulates
sequence tether, trophoblast hCG
constrict or production
amputate Thyrotropin Hypothalamus - Unknown
fetal parts GHRH Hypothalamus - Unknown
• Cause limb Growth - GH variant not Potentially
reduction hormone found in mediates pregnancy
defects, variant pituitary insulin resistance
facial clefts Neuropeptide Brain Potential
or Y regulations CRH
encephaloc release by
ele trophoblasts
Amnionic • Formed by normal amniochorion draped over a Parathyroid - Regulates transfer
sheet preexisting uterine synechia releasing of calcium and
• Pose little fetal risk protein other solutes
Slightly higher rates of PROM and abruptio Regulates fetal
mineral
homeostasis
ABNORMALITIES OF THE MEMBRANES Inhibin Ovary / testis Potentially inhibits
MECONIUM STAINING FSH mediated
ovulation
• Staining of the amnion can be obvious within 1-3 hours Regulates hCG
• Chorioamnionitis synthesis
o Ascending infection Activin Ovary / testis Regulates placental
• Other membrane abnormalities GnRH synthesis
o Amnion nodosum: numerous small light tan
nodules on the amnion overlying the
chorionic plate
o Amnionic band: early rupture of the amnion
results in adherence of part of the fetus to the
underlying “sticky” chorion

ABNORMALITIES OF THE UMBILICAL CORD

LENGTH:
• 40-70cm long
• Influenced by both amnionic fluid volume and fetal
mobility
• Short cords: fetal growth restriction, congenital
malformations, intrapartum distress
• Excessively long cords: cord entanglement or prolapse
COILING
• Hypocoiling: linked with fetal demise
• Hypercoiling: fetal growth restriction and intrapartum
PROTEIN HORMONES PRODUCED BY THE HUMAN PLACENTA fetal acidosis
HORMONE Primary non- Shares Functions VESSEL NUMBER
placental site structural or
• Two thick-walled arteries, one thin larger umbilical vein
of expression function
similarity • Fetus with major malformations frequently have a
HCG - LH, FSH, TSH Maintains CL single umbilical artery
Regulates fetal o Most frequent anomalies: cardiovascular and
testis testosterone genitourinary
secretion o Fetal growth restriction
Stimulates maternal REMNANTS AND CYSTS
thyroid
• Along the course of the cord
Placental - GH, prolactin Aids maternal
Lactogen adaptation to fetal • True cysts: epithelium lined remnants of the allantoic or
energy req vitelline ducts and tend to be located closer to the fetal
ACTH Hypothalamus - insertion site
CRH Hypothalamus - Relaxes smooth • Pseudocysts from local degeneration of Wharton jelly
muscle and occur anywhere along the cord
Initiates parturition INSERTION
Promotes fetal and • Marginal insertion / battledore placenta: cord anchors
maternal
at the placental margin
glucocorticoid
o Common in multifetal pregnancy
18
 • Vasa previa: velamentous insertion in which the vessel o Cranial end of the neural tube closes 38 days
within the membranes overlie the cervical os from the LMP
KNOTS, STRICTURES AND LOOPS o Caudal end of the neural tube closes 40 days
• True knots: caused by fetal movement, 1% of births from the LMP
o In singleton: stillbirth risk is increased four to • 8th week: CRL is approx. 22mm, fingers and toes are
tenfold present, arms bend at the elbows, upper lip is
• False knots: no clinical significance and appear as knobs complete, and the external ears form definitive
protruding from the cord surface elevations
o Focal redundancies of a vessel or Wharton • End of embryonic period signified completion of
jelly primary and secondary neuralization
• Cord stricture: focal narrowing of its diameter that Fetal Period
usually develops near the fetal cord insertion • Transition from the embryonic period to the fetal
o Stillborn period occurs at 7 weeks after fertilization or 9 weeks
• Cord loops: coiling around various fetal parts during after onset of last menses
movement • Fetus is approx. 24mm in length and most organs have
VASCULAR developed
• Umbilical artery aneurysm is caused by congenital • Enters a period of growth and maturation
thinning of the vessel wall with diminished support
from Wharton jelly AOG CRL/Fetal wt. Remarks
o Associated with trisomy 18, amnionic fluid 12 wks. CRL: 5-6cm o External genitalia are beginning to show
abnormalities, fetal growth restriction and definitive signs of male or female
stillbirth o Fetus makes spontaneous movements
16 wks. 150g o Eye movements
18 wks. o Female: uterus is formed, vaginal
canalization begins
CHAPTER 7 20 wks. 300g o Male: testicles descend
o Brown fat forms
Embryogenesis and Fetal Development 24 wks. 700g o Skin is wrinkled
o Fat deposition begins
AGING Survival o Secretory type II pneumocytes have
ACOG recommendations: rate: initiated surfactant secretion
50% o Canalicular period of lung development
1. First trimester sonography is the most accurate method
(during which bronchi and bronchioles
to establish gestational age enlarge and alveolar ducts develop) is
2. If assisted → first trimester utz nearly complete
o Terminal sacs have not yet formed*
EMBRYONIC DEVELOPMENT 28 wks. 1100g o Thin skin is red and covered with vernix
Zygote and Blastocyst Development caseosa
• During the first 2 weeks after ovulation and then Survival o Isolated eye blinking peaks
rate: o BM becomes the major site of
fertilization the zygote develops to the blastocyst stage
90% hemopoiesis
• Blastocyst implants 6 or 7 days following fertilization 32 and 32wks: 1800g o Subcutaneous fat deposition
• 58 cell blastocysts differentiates into 5 embryo- 36wks 36 wks.:
producing cells – the inner cell mass – and the 2800g
remaining 53 cells for the placental trophoblast 40 wks. CRL: 36cm o Term
3500g

Embryonic Period • But! CRL is not measured beyond 13 weeks (approx.

• Termed embryo at the beginning of the 3rd week
• Lasts 6 weeks
• Embryogenesis 3-8th week
• 3rd week: fetal blood vessels in the chorionic villi appear
• 4th week: cardiovascular system has formed
o Neural plate forms and subsequently folds to
form the neural tube
• 5th week: chorionic sac measures 1cm in diameter,
embryo is 3mm long
o Development of arm and leg buds
o Amnion begins to ensheathe the body stalk
which thereafter becomes the umbilical cord
• 6th week: embryo measures 9mm long, neural tube has
closed
o Cardiac motion is discernable
8.4cm) instead biparietal diameter, HC, AC and FL are
measured
• *Fetus delivered at this age will try to breathe but will
not survive 
CNS DEVELOPMENT
Brain Development
• Cranial end of the neural tube closes 38 days from the
LMP
• Caudal end of the neural tube closes 40 days from the
LMP
o FOLIC ACID IS IMPT TO PREVENT NEURAL
TUBE DEFECTS
• Walls of the neural tube form the brain and spinal cord
• Lumen becomes the ventricular system of the brain and
the central canal of the spinal cord

19
 • 6th week: cranial end of the NT forms 3 primary vesicles
• 7th week: 5 secondary vesicles develop
o Telencephalon: cerebral hemispheres
o Diencephalon: thalami
o Mesencephalon: midbrain
o Metencephalon: pons and cerebellum
o Myelencephalon: medulla
• 3-4 months: neuronal proliferation peaks
o Movement of millions of neuronal cells from
their ventricular and subventricular zones to
areas of the brain in which they reside for life
• 6 months: myelination of the ventral roots of the
cerebrospinal nerves and brainstem
• Spinal cord:
o Inferior third of the neural tube
o By 24 weeks: extends to S1
o At birth extends to L3
o Adult: to L1
o Myelination begins midgestation and
continues through the 1st year of life
• th
8 week – synaptic function
FETAL CIRCULATION
• Oxygen and nutrients are delivered from the placenta
by the umbilical vein
• Vein divides into the ductus venosus and portal sinus
• Ductus venosus is the major branch of the umbilical
vein and traverses the liver → IVC (so it carries well-
oxygenated blood directly to the heart)
• Portal sinus: carries blood to the hepatic veins on the
left side of the liver and oxygen is extracted
• Deoxygenated blood from the liver then flows back to
the IVC (which also receives more deoxygenated blood
from the lower body)
• So, blood from the IVC flowing thru the heart is a
mixture of oxygenated and deoxygenated blood
• Ventricles of the fetal heart work in parallel
• *Well oxygenated blood enters the LV (supplies the
heart and brain) [courses along the medial aspect of the
IVC]
o Once this blood enters the RA → crista
dividens shunts oxygenated blood from the
medial side of the IVC and the DV thru the
foramen ovale → left heart → heart and brain
→ exchange of oxygen → deoxygenated
heart returns to the RA thru SVC
• *Less oxygenated blood enters the RV (supplies the rest
of the body) [courses along the lateral side of the IVC]
o Enters the RA → thru the tricuspid valve →
RV
o SVC courses inferior and anteriorly as it enters
the RA ensuring that less well-oxygenated
blood from the brain and upper body will also
be shunted directly into the RV
o Blood in the RV is 15-20% less saturated than
blood in the LV
• These 2 separate circulations (* + *) aids in shunting
into opposite sides of the heart
• 90% of blood exiting the RV → ductus arteriosus (1/3 of
blood passing through the DA is delivered to the
body)→ descending aorta
• Only 8% of blood exiting the RV goes to the lungs
CIRCULATORY CHANGES AT BIRTH
• After birth: umbilical vessels, ductus arteriosus,
foramen ovale and ductus venosus normally constrict or
collapse
• Closure of the DA and expansion of the lungs: blood
leaving the RV enters the pulmonary vasculature to
become oxygen before it returns to the left heart
• Ventricles (before in parallel) now becomes in series
• More distal portions of the hypogastric arteries
undergo atrophy and obliteration within 3-4 days after
birth → umbilical ligaments
• Intrabdominal remnants of the UV → ligamentum teres
• DV constricts by 10-96 hours after birth and closes
anatomically by 2-3 weeks after birth → ligamentum
venosum
FETOPLACENTAL BLOOD VOLUME
• 125ml/kg of EFW
• Immediate cord clamping: 78ml/kg, fetal BV in placenta:
45ml/kg
HEMOPOIESIS
• Yolk sac → liver → spleen → bone marrow
• First erythrocytes released into the circulation are
nucleated and macrocytic
• MCV 180fL in embryo and decreases to 105-115fL at
term
• If with aneuploidy they do not undergo maturation and
maintain high MCVs of 130fL
• With fetal growth: BV and Hgb concentration increase
• Fetal erythrocytes have a short life span which
progressively lengthens to approx. 90 days at term
• Reticulocytes decrease to 4-5% of the total at term
• Erythropoiesis is controlled primarily by fetal EPO
(maternal EPO does not cross the placenta)
• EPO levels rise with fetal maturity
FETAL HEMOGLOBIN
• Normal adult hgb A is made of alpha and beta chains
• Embryonic and fetal life various alpha and beta chain
precursors are produced
• Beta type chains are on Chromosome 11
• Alpha chains are on chromosome 16
• Each of these alpha and beta chains are turned on and
off during fetal life until alpha and beta genes direct the
production of HgbA
• Yolk sac: Hgbs Gower 1 and 2 and Portland are made
• Liver: Hgb F
• BM: adult type hemoglobin A appears in fetal RBCs and
is present in progressively greater amounts as the fetus
matures
• Final adult version of the alpha chain is produced
exclusively by 6 weeks
• At birth approx. ¾ of total Hgb levels are Hgb F
• During first 6-12 months of life: Hgb F continues to
decline and eventually reaches the low levels
COAGULATION FACTORS
• Fetus starts producing normal adult-type procoagulant,
fibrinolytic and anticoagulant proteins by 12 weeks
20
 • In normal neonates: levels of factors 2, 7, 9, 10, 11,
protein S, protein C, antithrombin and plasminogen all
approximate 50% of adult levels
• Factors 5, 8, 13 and fibrinogen are closer to adult values
RESPIRATORY SYSTEM
• Pseudoglandular stage: growth of the intrasegmental
bronchial tree between the 5th and 17th week
• Canalicular stage: 16-25 weeks, bronchial cartilage
plates extend peripherally; each terminal bronchiole →
several respiratory bronchioles → multiple saccular
ducts
• Terminal sac stage: after 25 weeks; alveoli give rise to
primitive pulmonary alveoli → terminal sacs
o Extracellular matrix develops from proximal
to distal lung segments until term
• Alveolar stage: late fetal period and continues into
childhood
o Extensive capillary network is built
o Lymph system forms
o Type II pneumocytes begin to produce
surfactant
• At birth: approx. 15% of the adult number of alveoli is
present; lung continues to grow adding more alveoli for
up to 8 years
Pulmonary Surfactant:
• Role of surfactant: After the first breath, terminal sacs
must remain expanded despite the pressure imparted
by the tissue-to-air interface, surfactant prevents them
from collapsing
• Line the alveoli
• Multivesicular bodies that produce the lamellar bodies
• At fetal life, alveolus is characterized by a water-to-
tissue interface, intact lamellar bodies secreted from
the lungs are swept into the amnionic fluid during fetal
breathing → at first breath: surfactant uncoils from the
lamellar bodies and spreads to line the alveolus
• Fetal lung capacity to produce surfactant establishes
lung maturity
• Composition:
o 90% lipid → 80% are phosphatidylcholines
(lecithins: dipalmitoylphosphatidylcholine)
▪ Phosphatidylglycerol: 8-15%
▪ Phosphatidylinositol
o 10% proteins
• Surfactant Synthesis:
o Apoproteins are produced in the ER
▪ Aid the forming and reforming of a
surface film
▪ Major apoprotein: surfactant A (SP-
A) 28,000-35,000 Da (mol weight)
→ content increases with
gestational age and fetal lung
maturity
• 29 weeks AOG
▪ SP-B and SP-C are important in
optimizing the action of surfactant
• Deletion of SP-B gene:
incompatible with survival
despite large amounts of
surfactant
o Glycophospholipids are synthesized by
cooperative interactions of several cellular
organelles
▪ Primary surface tension=lowering
component of surfactant
• Breathing
o Fetal respi muscles develop early, chest wall
movements are detected as early as 11 weeks
o 4th month: fetus engages in respiratory
movement sufficiently intense to move
amnionic fluid in and out of the respiratory
tract
DIGESTIVE SYSTEM
STOMACH AND INTESTINES
• Foregut: gives rise to the pharynx, lower respiratory
system, esophagus, stomach, proximal duodenum, liver,
pancreas and biliary tree
• Midgut: duodenum, jejunum, ileum, cecum, appendix,
right colon
• Hindgut: left colon, rectum, superior portion of the anal
canal
• Swallowing begins at 10-12 WEEKS → neonates born
prematurely may have swallowing difficulties because
of immature gut mobility
• Most AF swallowed → lower colon
• Late in pregnancy: approx. 800mg of soluble protein is
ingested daily by the fetus
• Fetal swallowing appears to have little effect on AFV
early in pregnancy
• Term fetuses swallow between 200 and 760ml per day
• Intrinsic factor detectable by 11 weeks
• Pepsinogen detectable by 16 weeks
• Meconium
o Consists of: glycerophospholipids from the
lung, desquamated fetal cells, lanugo, scalp
hair and vernix, undigested debris from
swallowed AF
o Dark greenish color forms from bile pigments
(esp. biliverdin)
o It can pass when hypoxia stimulates arginine-
vasopressin (AVP) release from the fetal
pituitary gland → stimulates colonic SM cells
to contract → intramnionic defecation
LIVER
• Hepatic diverticulum is an outgrowth of the
endodermal lining of the foregut
• Serum liver enzymes increase with gestational age
• Because of hepatic immaturity: preterm NB is at
particular risk for hyperbilirubinemia
• Lifespan of normal fetal macrocytic erythrocytes is
shorter than the adult → more unconjugated bilirubin is
produced
• Fetal liver conjugates only a small fraction → excreted
into the intestines → oxidized to biliverdin
• Most of the unconjugated bilirubin is excreted into the
AF after 12 weeks and is transferred across the placenta
• Most fetal cholesterol derives from hepatic synthesis =
large amounts of LDL
PANCREAS
21
 • Arises from dorsal and ventral pancreatic buds from the • Pit-thyroid system is functional by the end of the 1 st
endoderm of the foregut trimester
• Glucagon at 8 weeks • Able to synthesize hormones by 10-12 weeks
• Insulin containing granules can be identified by 9-10 • Thyrotropin, thyroxine and TBG detected at 11 weeks
weeks • Congenital hyperthyroidism develops when maternal
• Insulin is detectable in fetal plasma at 12 weeks TSH crosses the placenta to stimulate the fetal gland to
• Enzymes present at 16 weeks secrete thyroxine = fetus with large goiters, tachycardia,
o Amylase at 14 weeks hepatosplenomegaly, hematological abnormalities,
o Cholecystokinin: released only after protein craniosynostosis and growth restriction
ingestion (not found in the fetus) • Placenta prevents passage of maternal thyroid
• Responds to hyperglycemia by secreting insulin hormones to the fetus by rapidly deiodinating maternal
T4 and T3 to form REVERSE T3 (inactive thyroid
URINARY SYSTEM hormone)
• Pronephros involutes by 2 weeks ADRENAL GLANDS
• Mesonephros produces urine at 5 weeks and • Medulla from neural crest ectoderm
degenerates by 11-12 weeks • Fetal and adult cortex arise from intermediate
• Failure of the pronephros and the mesonephros to form mesoderm
or to regress may result in anomalous urinary system • Grows rapidly through cell proliferation and
development angiogenesis, cellular migration, hypertrophy and
• 14 weeks: loop of Henle is functional, and reabsorption apoptosis
occurs
• New nephrons continue to be formed until 36 weeks IMMUNE SYSTEM
• GFR increases with AOG from less than 0.1ml/min at 12 • Fetal plasma Ig consist almost totally of transferred
weeks to 0.3ml/min at 20 weeks maternal IgG
• Fetal kidneys start urine production at 12 weeks IG Remarks Adult Levels by:
• By 18 weeks: 7-14ml/day IgG • Maternal IgG transport to the 3 years old
• At term: 650ml/day fetus at 16 weeks and increases
• Maternally administered furosemide increases fetal thereafter
urine formation • Bulk of IgG is acquired during the
• Uteroplacental insufficiency, fetal growth restriction last 4 weeks of pregnancy
and fetal disorders decrease urine flow IgM • Very little IgM is produced by 9 months
normal fetuses
• With infection = IgM response is
ENDOCRINE GLAND DEVELOPMENT dominant in the fetus and
PITUITARY GLAND remains so for weeks to months
• Anterior PG develops from oral ectoderm – Rathke in the NB
pouch • IgM levels in the UC may be
o Has 5 cell types that produce 6 protein useful in fetal infection diagnosis
hormones IgA • Provides mucosal protection
Cell Type Hormone First Detected at: against enteric infections
Lactotropes Prolactin 17 weeks
Somatotropes GH 13 weeks
Corticotropes ACTH 7 weeks LYMPHOCYTES AND MONOCYTES
Thyrotropes TSH 17 weeks • B lymphocytes appear in fetal liver by 9 weeks, blood
Gonadotropes LH and FSH LH: 13 weeks and spleen by 12 weeks
• T lymphocytes begin to leave the thymus at 14 weeks
• Posterior PG develops from neuroectoderm • NB responds poorly to immunization and especially
o Well developed by 10-12 weeks poorly to bacterial capsular polysaccharides
o Oxytocin and arginine vasopressin are well
developed
o Vasopressin levels in umbilical cord plasma
are increased vs maternal levels
• Intermediate lobe is well developed but disappear
before term and are absent from adult pituitary: MUSCULOSKELETAL SYSTEM
secretes alpha melanocyte stimulating hormone and • Origin is mesodermal
beta endorphin • By the end of the embryonic period, ossification centers
THYROID GLAND have developed, and bones harden by endochondral
• Arises from the endoderm of the 2nd pharyngeal pouch ossification
• Migrates to its final position and the obliterated • Limb buds appear by the 4th week
thyroglossal duct connect to the foramen cecum of the
tongue ENERGY AND NUTRITION

22
 • Growth of the embryo fetus is dependent on maternal amino acid transporters and modulates
nutrients during the first 2 months transfer across the placenta
• First few days after implantation, blastocyst nutrition • IONS AND TRACE METALS
comes from the interstitial fluid of the endometrium o Calcium and Ph are transported from mother
and the surrounding maternal tissue to fetus
3 MAJOR MATERNAL STORAGE DEPOTS: o Most common source of environmental
• Liver, muscle and adipose tissues cadmium is cigarette smoke
• Maternal insulin secretion is sustained by increased • VITAMINS
serum levels of glucose and amino acids o Vitamin A is greater in fetal than in maternal
• Storage of maternal fat peaks in the 2nd trimester then plasma
declines as fetal energy demands rise in the 3rd PLACENTAL ROLE IN EMBRYOFETAL DEVELOPMENT
trimester • After 10 weeks: 10-15% of cell-free DNA in maternal
GLUCOSE AND FETAL GROWTH plasma is placental in origin
• Midpregnancy: fetal glucose concentration is THE INTERVILLOUS SPACE (IVS)
INDEPENDENT from maternal levels • Maternal blood in the IVS is the primary source of
• GLUCOSE is the majority nutrient for fetal growth and maternal-fetal transfer
energy PLACENTAL TRANSFER
• hPL found in maternal blood has an insulin antagonistic • Syncytiotrophoblast actively or passively permits,
effect and blocks the peripheral uptake and use of facilitates and adjusts amount and rate of substance
glucose while promoting mobilization and use of FFA by transfer to the fetus
maternal tissues • Maternal facing SNCTB is characterized by a complex
• Glucose Transport microvillous structure
o Transfer of d-glucose across cell membranes MECHANISMS OF TRANSFER
via facilitated diffusion • Molecular mass <500Da pass readily through placental
o GLUT encoded by the SLC2A gene family are tissue by simple diffusion
characterized by tissue-specific distribution o Oxygen, CO2, water, most electrolytes and
o GLUT1 and GLUT3 facilitate glucose uptake by anesthetic gases
the placenta and are located in the plasma • Insulin, steroid hormones and thyroid hormones cross
membrane of the syncytiotrophoblast the placenta very slowly
o GLUT3 is upregulated with fetal growth • High molecular weight substances usually do not
restriction traverse the placenta EXCEPT IgG (160,000Da) by a
o Lactate (product of glucose metabolism) is specific trophoblast-receptor-mediated-mechanism
transported across the placenta via facilitated TRANSFER OF O2 AND CO2
diffusion • Placenta is highly permeable to CO2 which traverses the
• Fetal Macrosomia chorionic villus by diffusion
o Fetal hyperinsulinemia is one driving force • Fetal blood has less affinity for CO2 thus favoring CO2
o Maternal obesity begets fetal macrosomia transfer from the fetus to the mother
• Leptin
o Contributes to angiogenesis, hemopoiesis,
osteogenesis, pulmonary maturation and CHAPTER 8
neuroendocrine, immune and reproductive
function Preconceptional Care
o Produced by the mother, fetus and placenta • Epileptic women should be advised to take 4mg folic
o 5% enters fetal circulation, 95% is transferred acid supplement
to the mother • First trimester antiepileptic monotherapy and the
o Begin at 34 weeks and are correlated with associated malformation risk:
fetal weight Valproate 9.3%
Phenobarbital 5.5%
Topiramate 4.2%
Clonazepam 3.1%
Carbamazepine 3%
Phenytoin 2.9%
Leviteracetam 2.4%
Oxcarbazepine 2.2%
Lamotrigine 2%
Gabapentin 0.7%
• FREE FATTY ACIDS AND TRIGLYCERIDES
o 15% of fetal body weight is fat IMMUNIZATION
• AMINO ACIDS • Killed bacteria or viruses in vaccines are not CI:
o Amino acid concentration in the UC > o Influenza, pneumococcus, hepatitis B,
maternal venous or arterial plasma meningococcus, rabies
o Trophoblastic mammalian target of rapamycin • Toxoids are OK for pre-pregnancy and during preg
complex 1 (mTORC1) regulates placental o Tetanus toxoid
23
 • Live attenuated are not recommended • Serum screening for NTD: 15-20 weeks
o VZV, MMR, polio, chickenpox, yellow fever • Fetal aneuploidy screening: 11-14 weeks
o 1 month or longer should ideally pass NUTRITIONAL COUNSELING
PARENTAL AGE Recommendations for total and rate of weight gain in pregnancy
• Teenage pregnancy: at risk for anemia, preterm Category (BMI) Total Wt. Gain Wt. Gain in 2nd/3rd
delivery, preeclampsia, STD (lb.) T
ENVIRONMENTAL EXPOSURES Underweight <18.5) 28-40 1 (1-1.3)
• Pica: may be a sign of iron deficiency Normal wt. (18.5-24.9) 25-35 1 (0.8-1)
Overwt (25-29.9) 15-25 0.6 (0.5-0.7)
CHAPTER 9 Obese (>30) 11-20 0.5 (0.4-0.6)
Prenatal Care
DIAGNOSIS OF PREGNANCY
• Amenorrhea is not a reliable pregnancy indicator until
CHAPTER 10
10 days or more after expected menses Fetal Imaging
• Syncytiotrophoblast produces hCG that increases TECHNOLOGY AND SAFETY:
exponentially during the first trimester following • Real-time image on the ultrasound screen is produced
implantation by sound waves that are reflected back from fluid and
o To prevent involution of the corpus luteum tissue interfaces of the fetus, amnionic fluid and
(CL is the principal site of progesterone placenta
formation during the first 6 weeks of • Dense tissue such as bone produces high velocity
pregnancy) reflected waves = bright echoes on the screen
o Detected 8-9 days after ovulation • Fluid generates few reflected waves and appears dark
o Doubling time is 1.4-2 days
• Ultrasound: sound waves traveling at a frequency above
o Peak levels at 60-70 days → plateau reached
20,000 hertz (cycles per second)
at 16 weeks
• Early pregnancy: 5-10 MHz transvaginal transducer
• Sonographic Recognition provides excellent resolution because the early fetus is
o GS – small anechoic fluid in the endometrial
close to the transducer
cavity
• First and 2nd trimester: 4-6MHz transabdominal
▪ FIRST SONOGRAPHIC EVIDENCE OF
• 3rd trimester: lower frequency (2-5MHz) for tissue
PREGNANCY
penetration
▪ 4-5 weeks
o First trimester utz is the MOST ACCURATE
METHOD to establish or reaffirm GA
FETAL SAFETY:
o If ART: embryo age or transfer date is used to
• ALARA principle: As Low As Reasonably Achievable
assign GA
CONDITIONS FOR WHICH MFM CONSULT MAY BE BENEFICIAL: • All sonography machines are required to display 2
Medical Hx and Conditions OB Hx and Conditions indices:
1. Cardiac disease – moderate to severe 1. Rh or other blood group o Thermal index: measure of the relative
2. DM with evidence of end-organ alloimmunization probability that the examination may raise
damage or uncontrolled hyperglycemia 2. Prior or current fetal the temperature potentially high enough to
3. Family or personal hx of genetic structural or induce injury
abnormalities chromosomal ▪ Tis (thermal index for soft tissue):
4. Hemoglobinopathy abnormality used before 10 weeks AOG
5. Chronic hpn if uncontrolled or asso 3. Desire or need for
▪ Tib (thermal index for bone): used
with renal or cardiac dis prenatal diagnosis or fetal
beyond 10 weeks
6. Renal insuff if asso with significant therapy
proteinuria ( 4. Periconceptional ▪ Higher with pulsed Doppler
7. >500mg/24 hrs.), serum crea >1.5mg/dl exposure to known applications than with routine B-
or hpn teratogens mode scanning
8. Pulmonary disease if severe restrictive 5. Infection with or ▪ If indicated in the 1st trimester
or obstructive (including severe exposure to organisms thermal index should be <0.7 with a
asthma) that cause congenital brief exposure only → that’s why M
9. HIV infection
mode is used instead of pulsed
10. Prior pulmo embolus or DVT 6. Higher order multifetal
11. Severe systemic dis (including gestation
Doppler imaging
autoimmune) 7. Severe disorders of o Mechanical index: measure of the likelihood
12. Bariatric surgery amniotic fluid volume of adverse effects related to rarefactional
13. Epilepsy if poorly controlled or pressure, such as cavitation – which is
requires more than 1 anticonvulsant relevant only in tissues that contain air
14. Cancer • The use of sonography as “keepsake” is considered
SCHEDULE OF PRENATAL VISITS “contrary to responsible medical practice” 
• Every 4 weeks until 28 weeks
• Every 2 weeks until 36 weeks → weekly thereafter OPERATOR SAFETY
NEURAL TUBE DEFECT AND GENETIC SCREENING To avert injury:

24
 1. Position the patient close to you on the examination o If <2.5th percentile for GA or shortened to
table (your elbow is close to your body, shoulder <90th percent of the expected based on
abduction is less than 30 degrees, thumb is facing up) measured BPD → minor marker for Down
2. Adjust table or chair height so forearm is parallel to the Syndrome
floor o Normal range of FL to AC ratio is generally 20-
3. If seated, use a chair with back support, support your 24% (if <18% prompts evaluation for a
feet and keep ankles in a neutral position skeletal dysplasia)
4. Face monitor squarely and view it at a neutral angle (!5 • AC – most affected by fetal growth
degrees downward) o For GA estimation, AC has the greatest
5. Avoid reaching, bending or twisting while scanning variation which can reach 2-3 weeks in the 2nd
6. Frequent breaks may prevent muscle strain, stretching trimester
and strengthening exercises o Image should appear as round as possible and
ideally contains no more than 1 rib on each
GESTATIONAL AGE ASSESSMENT: side of the abdomen and kidneys should not
• The only exception to revising the gestational age based be visible
on early sonography is if the pregnancy is ART in which • Variability of the sonographic GA estimate increases
case, accuracy of GA assessment is presumed with advancing gestation
• CRL is the most accurate method to establish or confirm • Pregnancies not imaged prior to 22 weeks to confirm or
GA revise GA are considered sub optimally dated
Sonographic GA Assessment
Gestational Age Parameters Threshold to Revise* Indications for 1st Trimester UTZ Examination
<9wks CRL >5d 1. Confirm an intrauterine pregnancy
9 to <14 wks. >7d 2. Evaluate a suspected ectopic pregnancy
14 to <16 wks. BPD, HC, >7d 3. Define cause of vaginal bleeding
16 to <22 wks. AC, FL >10d 4. Evaluate pelvic pain
22 to <28 wks. >14d 5. Estimate GA
>28 weeks >21d 6. Diagnose or evaluate multifetal gestations
*Sonographic GA should be used when the LMP derived GA 7. Confirm cardiac activity
differs from that obtained with sonography by the threshold 8. Assist chorionic villus sampling, embryo transfer and
value localization and removal of an IUD
• CRL is measured in the midsagittal plane with the 9. Assess for certain fetal anomalies (anencephaly in high
embryo or fetus in a neutral nonflexed position so that risk patients)
its length can be measured in a straight line 10. Evaluate maternal and pelvic masses and/or uterine
o Should not include yolk sac nor a limb bud abnormalities
o Until 13 6/7 weeks AOG, the CRL is accurate 11. Measure NT when part of a screening program for fetal
to within 5-7 days aneuploidy
• Starting at 14 weeks: BPD, HC, AC and FL are used 12. Evaluate suspected GTD
o May over or underestimate fetal weight by up
to 20% FIRST TRIMESTER SONOGRAPHY
• BPD most accurately reflects GA with a variation of 7-10
days in the 2nd trimester • Can reliably diagnose anembryonic pregnancy,
o Measured perpendicular to the midline falx in embryonic demise, ectopic pregnancy and GTD
the transthalamic view at the level of the • Ideal time to evaluate the uterus, adnexa and cul-de-sac
thalami and cavum septum pellucidum (CSP) • Determination of chorionicity in a multifetal gestation is
o Measured outer edge of the skull in the near most accurate
field to the inner edge of the skull in the far • An intrauterine GS is reliably visualized with VS by 5
field weeks, embryo by 6 weeks
o Cephalic index (BPD divided by the OFD): • Embryo is visible when the mean sac diameter has
normally 70-86% reached 25mm (otherwise it is anembryonic)
o Abnormalities in head shape: • Cardiac motion visible when embryo length reaches
▪ Dolicephaly (flat): can occur with 5mm
NTD • In embryos <7mm without cardiac activity, subsequent
▪ Brachycephaly (rounded): Down examination may be needed to determine viability
Syndrome • First trimester demise is diagnosed if the embryo has
▪ Craniosynostosis and other reached 10mm and lacks cardiac motion
craniofacial abnormalities
• FL correlates well with both BPD and GA
o Measured with the beam perpendicular to the
long axis of the shaft Nuchal Translucency:
o Has a variation of 7-11 days in the 2nd • The maximum thickness of the SC translucent area
trimester between the skin and soft tissue overlying the fetal
spine at the back of the neck
25
 • Measured in the sagittal plane between 11 and 14
weeks AOG
• Increased NT = increased risk for fetal aneuploidy and
various structural anomalies – in particular, heart
defects
Guidelines for NT Measurement
1. Margins of NT edges must be clear enough for proper
caliper placement
2. Fetus must be in mid sagittal plane
3. Image must be magnified so that it is filled by the fetal
head, neck and upper thorax
4. Fetal neck must be in a neutral position, not flexed, not
hyperextended
5. Amnion must be seen as separate from the NT line
6. Electronic calipers must be used to perform the
measurement
7. The + calipers must be placed on the inner borders of
the nuchal space with none of the horizontal crossbar
itself protruding into the space
8. Calipers must be placed perpendicular to the long axis
of the fetus
9. Measurement must be obtained at the widest space of
the NT
Fetal Anomaly Detection
• Focus on anatomy visible at 11-14 weeks AOG
SECOND AND THIRD TRIMESTER SONOGRAPHY
• Recommended that sonography be routinely offered to
all pregnant women between 18 and 22 weeks AOG
• Permits accurate assessment of AOG, fetal anomaly,
placental location and cervical length
• 3 examination types: standard, specialized and limited
• Standard: evaluation of fetal number and presentation,
cardiac activity, AFV, placental position, fetal biometry
and fetal anatomy, number of chorions and amnions,
comparison of fetal sizes, estimation of AFV within each
sac and fetal sex determination
• Specialized: targeted scan, performed when the risk for
a fetal anatomical or genetic abnormality is elevated
because of history, screening test result or abnormal
finding during standard examination
o Indication driven and should not be repeated
later in the absence of an extenuating
circumstance
o Other types: fetal echocardiography, doppler
evaluation and BPS
• Limited: performed to address a specific clinical
question
o Evaluation of fetal presentation
o Viability
o AFV or placental location
o Only done if a standard sonogram has already
been completed
Fetal Anomaly Detection:
• Approximately 50% are detected with standard
sonography
Amnionic Fluid Volume:
• Oligohydramnios: AF below normal range and
subjective crowding of the fetus is often noted
• Hydramnios: volume above a given normal threshold
• SVP or sum of the deep vertical pockets from each of
the four equal uterine quadrants
• SVP: 2-8cm
• AFI: 8-24cm
Cervical Length Assessment:
• Full bladder may artificially elongate the appearance of
the cervix
• Only CL measurements obtained transvaginally at or
beyond 16 weeks are considered sufficiently accurate
for clinical decision making
• Funneling: protrusion of amnionic membranes into a
portion of the endocervical canal that has dilated
o Not an independent predictor of preterm
birth however, it is associated with cervical
shortening and TVS is recommended if
suspected transabdominally
NORMAL AND ABNORMAL FETAL ANATOMY
Brain and Spine
• Includes 3 transverse (axial) views
• Transthalamic view is used to measure the BPD, HC and
includes the midline falx, cavum septum pellucidum
(CSP) and thalami
• CSP: space between the 2 laminate that separate the
frontal horns of the lateral ventricles
• Inability to visualize a normal CSP may indicate a
midline brain abnormality such as agenesis of the
corpus callosum, lobal holoprosencephaly or septo-
optic dysplasia
• Transventricular view: includes lateral ventricles which
contain the echogenic choroid plexus
• Transcerebellar view: obtained by angling the
transducer back through the posterior fossa
o Cerebellum and cisterna magna are measured
o From 15-22 weeks AOG, the cerebellar
diameter in mm is roughly equivalent to the
GA in weeks
o Cisterna magna normally measures 2-10mm
▪ Effacement is present in the Chiari II
malformations
• Imaging of the spine: transverse images demonstrate 3
ossification centers
Neural Tube Defects:
• Anencephaly, myelomeningocele (AKA spina bifida),
cephalocele, and other rare spinal fusion abnormalities
• Result from incomplete closure of the NT by the
embryonic age of 26 to 28 days
• Can be prevented with folic acid supplementation
• Recurrence risk without periconceptional folic acid is 3-
5%
• Screening with maternal serum alpha-fetoprotein
(MSAFP) has been offered routinely as part of prenatal
care
26
 • MSAFP is performed between 15-20 weeks AOG
• Anencephaly: absence of the cranium and telencephalic
structures above the level of the skull base and orbits
• Arcania: absence of cranium with protrusion of the
disorganized brain tissue
o Inability to visualize the BPD raises suspicion
• Cephalocele: herniation of meninges through a cranial
defect located in the midline occipital region
o Encephalocele: when brain tissue herniates
through the skull defect
o Chiari III malformation: herniation of the
cerebellum and other posterior fossa
structures
o Meckel Gruber syndrome: cephalocele is an
important feature of this autosomal recessive
disease which includes cystic renal dysplasia
and polydactyly
o Amnionic band sequence: if cephalocele is
not located in the occipital midline
• Spina bifida: defect in the vertebrae, typically the
dorsal arches with exposure of the meninges and spinal
cord
o Most are open spinal bifida – the defect
includes the skin and soft tissues
o Myelomeningocele: herniation of a
meningeal sac containing neural elements
o Meningocele: only meningeal sac protrudes
o Aided by 2 characteristics:
▪ Lemon sign: scalloping of the frontal
bones
▪ Banana sign: anterior curvature of
the cerebellum with effacement of
the cisterna magna (at the posterior
fossa)
o Detection of spina bifida are findings in the
Chiari II malformation (Arnold-Chiari
Malformation) which develops when
downward displacement of the spinal cord
pulls a portion of the cerebellum through the
foramen magnum and into the upper cervical
canal
Ventriculomegaly
• Distention of the cerebral ventricles by CSF
• Nonspecific marker of abnormal brain development
• Atrium normally measures 5-10mm from 15 weeks AOG
until term
o Mild: if >15mm
o Larger the atrium, the greater the likelihood
of an abnormal outcome
• CSF is produced within the ventricles by the choroid
plexus – it appears to dangle within the ventricle when
severe ventriculomegaly is present
• May be due to CNS abnormalities such as Dandy Walker
malformation or holoprosencephaly
• May be due to an obstructive process such as
aqueductal stenosis
• May be due to a destructive process – porencephaly or
an intracranial teratoma
• Initial testing includes: TORCH panel
Agenesis of the Corpus Callosum
• Corpus callosum: major fiber bundle connecting the
reciprocal regions of the cerebral hemispheres
• With complete agenesis, a normal cavum septum
pellucidum cannot be visualized Sonographically
• Frontal horns are displaced laterally, and atria show
mild enlargement posteriorly (teardrop appearance)
Holoprosencephaly
• In early normal brain development, the prosencephalon
(forebrain) divides as it becomes the telencephalon and
diencephalon
• Holoprosencephaly – the prosencephalon fails to divide
completely into 2 separate cerebral hemispheres
• Types: alobar, semi lobar and lobar
• Alobar holoprosencephaly: most severe form
o A single monoventricle with or without a
covering mantle of cortex surrounds fused
central thalami
• Semilobar: partial separation of the hemispheres
occurs
• Lobar: variable degree of fusion of frontal structures
and should be considered when a normal CSP cannot be
seen
Dandy Walker Malformation – Vermian Agenesis
• Posterior fossa abnormality
• Characterized by agenesis of the cerebellar vermis,
posterior fossa enlargement and elevation of tentorium
• Associated with numerous genetic and sporadic
syndromes, congenital viral infections and teratogen
exposure
• Inferior vermian agenesis / Dandy Walker variant – only
the inferior portion of the vermis is absent
Schizencephaly and Porencephaly
• Schizencephaly: rare brain abnormality characterized by
clefts in one or both cerebral hemispheres involving the
perisylvian fissure
o Abnormality of neuronal migration
o Absence of cavum septum pellucidum →
frontal horn communication
• Porencephaly: cystic space within the brain lined by
white matter and may or may not communicate with
the ventricular system
o Destructive lesion
o May develop following intracranial
hemorrhage in the setting of a neonatal
alloimmune thrombocytopenia or following
death of a monochorionic co-twin
Sacrococcygeal Teratoma
• Germ cell tumor
• One of the most common tumors in neonates
• Arises from the totipotent cells along Hensen node,
anterior to the coccyx
• Type 1: predominantly external with a minimal
presacral component
• Type 2: predominantly external but with a significant
intrapelvic component
• Type 3: predominantly internal but with abdominal
extension
• Type 4: entirely internal with no external component
• Tumor type may be mature, immature or malignant
27
 • Sonographically appears solid and/or cystic mass that
arises from the anterior sacrum and extends inferiorly
and externally as it grows
• Hydramnios is common and hydrops may develop from
high output cardiac failure
• If SCT >5cm → CS and/or classical hysterotomy
Caudal Regression Sequence – Sacral Agenesis
• Characterized by absence of the sacral spine and often
portions of the lumbar spine
• 25x more common in diabetic pregnancies
• Spine that appears abnormally short, lacks normal
lumbosacral curvature and terminates abruptly above
the level of the iliac wings
Face and Neck
Facial Clefts
• 3 main types of cleft
o Cleft lip and palate: always involve the lip, ma
also involve the hard palate, can be unilateral
or bilateral
▪ Rate of associated anomalies is
highest for bilateral defects that
involve the palate
▪ May offer fetal chromosomal
microarray analysis
o Isolated cleft palate: begins in the uvula, may
involve the soft palate and occasionally
involves the hard palate – but does not
involve the lip
o Median cleft lip: found in association with
agenesis of the primary palate, hypotelorism
and holoprosencephaly
Cystic Hygroma
• Venolymphatic malformation
• Fluid filled sacs that extend from the posterior neck
• Develops when lymph from the head fails to drain into
the jugular vein and accumulates instead in jugular
lymphatic sacs
• 70% are associated with aneuploidy
• When diagnosed in the 1st trimester → trisomy 21 is the
most common followed by 45, X and trisomy 18
o 5x more likely to be aneuploid vs fetuses with
a thickened NT
• When diagnosed in the 2nd trimester → 45, X (Turner
syndrome) is the most common
• Even in the absence of aneuploidy, still high risk for
other anomalies (cardiac diseases that are flow related
→ hypoplastic left heart and CoA)
• May be part of a genetic syndrome (Noonan syndrome)
→ autosomal dominant disorder that shares several
features with Turner syndrome including short stature,
lymphedema, high arched palate and pulmonary valve
stenosis
• Large sizes are usually associated with hydrops and
rarely resolve
Thorax
• Lungs appear homogenous in ultrasound
Congenital Diaphragmatic Hernia
• Defect in the diaphragm through which abdominal
organs herniate into the thorax
• Left sided in 75% of cases, right sided in 20% and
bilateral in 5%
• Associated anomalies are found in 40% of cases
• Targeted sonography and fetal echo should be
performed
• If there are no associated abnormalities, the major
causes of neonatal mortality are pulmonary hypoplasia
and pulmonary hypertension
Congenital Cystic Adenomatoid Malformation
• Overgrowth of terminal bronchioles that communicates
with the tracheobronchial tree
• AKA congenital pulmonary airway malformation (CPAM)
• Well circumscribed thoracic mass that may appear solid
and echogenic or may have one or multiple variably
sized cysts
• Usually involves one lobe, has blood supply from the
pulmonary artery and drains into the pulmonary veins
• Lesions with cysts >5mm are macrocystic
• Lesions <5mm are microcystic
• Overall survival rate >95%
Pulmonary Sequestration
• AKA bronchopulmonary sequestration
• Accessory lung bud “sequestered” from the
tracheobronchial tree ~ mass of nonfunctioning lung
tissue
• Most cases are extralobar (enveloped in their own
pleura)
• Most cases in adults are intralobar (within the pleura of
another lobe)
• Left sided predominance
• Presents as a homogenous echogenic thoracic mass
• Blood supply is from the aorta (vs pulmonary artery in
CCAM)
Congenital High Airway Obstruction Sequence
• Rare
• Usually results from laryngeal or tracheal atresia
• Normal egress of lung fluid is obstructed →
tracheobronchial tree and lungs become massively
distended → venous return is impaired → ascites,
hydrops
• Feature of Fraser syndrome – an autosomal recessive
syndrome
Heart
• Cardiac malformations are the most common class of
congenital anomalies
• 90% are multifactorial or polygenic in origin
• 1-2% from single gene disorder o gene deletion
• 1-2% exposure to a teratogen such as isotretinoin,
hydantoin or maternal diabetes
• Trisomy 21 accounts for >50% of cases
28
Basic Cardiac Examination
• Standard assessment includes a 4 chamber view,
evaluation of rate and rhythm and evaluation of the left
and right ventricular outflow tracts
• Four chamber view: transverse image of the fetal
thorax immediately above the diaphragm
o Allows evaluation of cardiac size, position,
axis, atria, ventricles, foramen ovale, atrial
septum, interventricular septum and AV
valves
• Left ventricular outflow tract view: VSDs are visible
• Right ventricular outflow tract view: RV and main
pulmonary artery
Fetal Echocardiography:
• If there is suspected fetal cardiac anomaly, extracardiac
anomaly, chromosomal abnormality, fetal arrhythmia,
hydrops, thick nuchal translucency, monochorionic twin
gestation, first degree relative to the fetus with a
congenital cardiac defect, IVF, maternal anti-Ro or anti-
La antibodies, exposure to a medication associated with
cardiac defects
Ventricular Septal Defect
• Most common congenital cardiac anomaly
• Prognosis for an isolated defect is good
Endocardial Cushion Defect
• AV septal defect or AV canal defect
• Associated with Trisomy 21
Hypoplastic Left Heart Syndrome
• Sonographically, left side of the heart may appear
“filled-in” or the LV may be so small and attenuated
that a ventricular chamber is difficult to appreciate
• Ductal dependent lesion for which neonatal
administration of prostaglandin therapy is essential
Tetralogy of Fallot
• VSD
• Overriding aorta
• Pulmonary valve abnormality (stenosis)
• Right ventricular hypertrophy
• If with pulmonary atresia or when the pulmonary valve
is absent → high risk for hydrops and tracheomalacia
(from compression of the trachea by an enlarged
pulmonary artery)
Cardiac Rhabdomyoma
• Most common cardiac tumor
• 50% are associated with tuberous sclerosis (autosomal
dominant disease with multiorgan system
manifestations caused by mutations in the hamartin
(TSC1) and tuberin (TSC2) genes
• Appear as well circumscribed echogenic masses within
the ventricles or outflow tracts
M Mode
• Motion mode or M mode
• Linear display of cardiac cycle events with time on the x
axis and motion on the y axis
• Useful for characterizing arrhythmias and their
response to treatment
• May also be used to assess ventricular function and
atrial and ventricular outputs
Premature Atrial Contractions
• Atrial extrasystole – most common fetal arrhythmia and
a frequent finding
• Represent cardiac conduction system immaturity and
typically resolve later in gestation or in the neonatal
period
• Associated with maternal caffeine consumption and
with hydralazine use
Abdominal Wall
• Assessed at the level of the cord insertion during the
standard examination
• Gastroschisis: full thickness abdominal wall defect
located to the right of the umbilical cord insertion
o Bowel herniates through the defect into the
amnionic cavity
o More common in fetuses of younger mothers
(average maternal age is 20 years old)
o Coexisting bowel abnormalities such as
jejunal atresia are found in approx. 15% of
cases
o Not associated with aneuploidy
o Fetal growth restriction is a complication
o Planned delivery at 36-37 weeks
• Omphalocele: forms when the lateral ectomesodermal
folds fail to meet in the midline covered only by a 2-
layered sac of amnion and peritoneum into which the
umbilical cord inserts
o More than half of cases are associated with
other major anomalies or aneuploidy
o Component of syndromes such as Beckwith-
Wiedemann, cloacal exstrophy and pentalogy
of Cantrell
o Smaller defects confer greater risk for
aneuploidy
• Body stalk anomaly
o Aka: limb-body wall complex or cyllosoma
o Rare and lethal anomaly characterized by
abnormal formation of the body wall
o No abdominal wall is visible, and the
abdominal organs extrude into the
extraamnionic coelom
Gastrointestinal Tract
• Stomach is visible in all fetuses after 14 weeks AOG
• Nonvisualization of the stomach may be secondary to
impaired swallowing in the setting of oligohydramnios
or an esophageal atresia, a craniofacial anomaly or a
CNS or musculoskeletal abnormality
• Bowel that appears as bright as fetal bone confers a
slightly greater risk for underlying GI malformations,
cystic fibrosis or Trisomy 21
Gastrointestinal Atresia
• Bowel atresia is characterized by obstruction and
proximal bowel dilation
• The more proximal the obstruction, the more likely it is
to lead to hydramnios
29
 • Esophageal atresia: may be suspected when the
stomach cannot be visualized and hydramnios is
present
o 90% of cases have a concomitant trachea-
esophageal fistula allowing fluid to enter the
stomach
o 10% of cases occur as part of VACTERL
(Vertebral defects, Anal atresia, Cardiac
defects, Tracheoesophageal fistula, Renal
anomalies and Limb abnormalities
• Duodenal atresia: sonographic double bubble sign
which represents distention of the stomach and the
first part of the duodenum
o Not present before 22 and 24 weeks
o Associated with Trisomy 21
Kidneys and Urinary Tract
• Kidneys are visible adjacent to the spine frequently in
the 1st trimester and routinely by 18 weeks AOG
• Length: 20mm at 20 weeks and grows about 1.1mm
each week thereafter
• Fetal ureters and urethra are not visible unless
abnormally dilated
• Fetal urine production rises from 5ml/hr. at 20 weeks to
approx. 50ml/hr. at term
Renal Pelvis Dilatation
• Hydronephrosis
• In 40-90% it is transient or physiological and does not
represent an underlying abnormality
• Confirmed in the neonatal period
• Most frequent – ureteropelvic junction (UPJ)
obstruction or vesicoureteral reflux (VUR)
• Renal pelvis is considered dilated if it exceeds 4mm in
the 2nd trimester or 7mm at approximately 32 weeks
AOG
• Mild pyelectasis in the 2nd trimester is considered a soft
marker for Down Syndrome
Uteropelvic Junction Obstruction
• Most common abnormality associated with renal pelvis
dilatation
• Obstruction is generally functional rather than
anatomical and is bilateral usually
Duplicated Renal Collecting System
• Upper and lower poles of the kidney (called moieties)
are each drained by a separate ureter
• Found in 1 in 4000 pregnancies, more common in
females and is bilateral in 15-20%
• Sonographically, an intervening tissue band separates
the 2 distinct renal pelves
Renal Agenesis:
• Prevalence of bilateral renal agenesis is 1 in 8000 births
• Prevalence of unilateral renal agenesis is 1 in 1000
births
• Lying down adrenal sign: absence of the kidney causes
the adrenal gland to enlarge and fill the renal fossa
• If bilateral → no urine is produced → anhydramnios →
pulmonary hypoplasia, limb contractures and a
compressed face
Multicystic Dysplastic Kidney
• Results to a nonfunctioning kidney
• Sonographically, the kidney contains numerous smooth
walled cysts of varying size that do not communicate
with the renal pelvis
• Unilateral has a good prognosis whereas bilateral is
associated with severely decreased AFV early gestation
leading to Potter sequence and a poor prognosis
Polycystic Kidney Disease
• Autosomal recessive polycystic kidney disease may be
reliably diagnosed prenatally
o Results in cystic dilatation of the renal
collecting ducts
o Mutation in the PKHD1 gene, 1 in 20,000
o Displays abnormally large kidneys that fill and
distend the fetal abdomen and have a solid,
ground glass texture
o Severe oligohydramnios confers a poor
prognosis
• Autosomal dominant polycystic kidney disease
o More common
o Does not manifest until adulthood
Bladder Outlet Obstruction
• More frequent in male fetuses
• Most common etiology is posterior urethral valves
Skeletal Abnormalities
• 2 types of skeletal dysplasias:
o Osteochondrodysplasias: the generalized
abnormal development of bone and/or
cartilage
o Dysotoses: abnormalities of individual bones
(polydactyly)
• Deformations (ex. Clubfoot)
• Disruptions (ex. Limb reduction defects)
Skeletal Dysplasias:
• Micromelia: involvement of all long bones
• Rhizomelia: involvement of only the proximal,
Mesomelia: involvement of the intermediate or
Acromelia: distal long bone segments
• Fibroblast growth factor 3 (FGFR3) chondrodysplasia
group
o Achondroplasia: AKA heterozygous
achondroplasia is the most common
nonlethal skeletal dysplasia
▪ Due to a specific point mutation in
the FGFR3 gene
▪ Autosomal dominant
▪ 80% of cases result from a new
mutation
▪ Long bone shortening that is
predominantly rhizomelic (an
enlarged head with frontal bossing,
depressed nasal bridge,
30
 exaggerated lumbar lordosis, trident
configuration of the hands)
▪ Intelligence is normal
▪ Not diagnosed until late in
pregnancy (sonographically femur
and humerus measurements may
not lie below the 5th percentile until
early 3rd T)
o Thanatophoric dysplasia: most common lethal
skeletal disorder
▪ Severe micromelia
▪ Cloverleaf skull deformity due to
craniosynostosis
• Osteogenesis imperfecta and decreased bone density
group
o Group of skeletal dysplasias typified by
hypomineralization
o Mutation in the COL1A1 or COL1A2 gene
o Type IIa – lethal
▪ Profound lack of skull ossification,
gentle pressure on maternal
abdomen from the utz transducer
results in visible skull deformation
▪ “beaded ribs” signify fractures
▪ Autosomal dominant
• Lethal dysplasias show profound long bone shortening
with measurements <5th percentile and display femur
length-to-abdominal circumference ratios below 16
percent
o Pulmonary hypoplasia if thoracic
circumference <80 percent of abdominal
circumference value
o May develop hydramnios and/or hydrops
Clubfoot – Talipes Equinovarus
• Deformed talus and shortened Achilles tendon
• Affected foot is abnormally fixed and positioned with
equinus (downward pointing), varus (inward rotation)
• Most are considered malformations
• 1 in 1000 births
• Male: female ratio is 2:1
• Bilateral in approximately 50% of affected individuals
• Associated anomalies present in at least 50% of all
cases (neural tube defects, arthrogryposis, myotonic
dystrophy and other genetic syndromes)
Limb Reduction Defects
• Absence or hypoplasia of all or part of one or more
extremities
• 4-9 in 10,000
• Upper ex > lower ex
• Transverse limb defect lacks part or all of a distal limb
to create a stump
o More common than longitudinal defect
(complete or partial absence of the long
bones)
• Absence of an entire limb – amelia
• Phocomelia – thalidomide exposure
o Absence of one or more long bones with the
hands or feet attached to the trunk
DOPPLER
• Doppler Shift: when sound waves strike a moving
target, the frequency of the waves reflected back is
shifted in proportion to the velocity and direction of
that moving target
• Can evaluate flow within blood vessels
Umbilical Artery
• Waveform is considered abnormal if the S/D ratio is
>95th percentile for gestational age
• Aids in the management of fetal growth restriction
• Not recommended for complications other than growth
restriction
Ductus Arteriosus
• To monitor fetuses exposed to indomethacin and other
NSAIDs – may cause ductal constriction or closure
particularly when used in the 3rd trimester
Uterine Artery
• Estimated to rise from 50mL/min early in gestation to
500-750mL/min by term
Middle Cerebral Artery
• Applied clinically for fetal anemia detection and fetal
growth restriction evaluation
• Imaged in an axial view of the head at the base of the
skull, ideally within 2mm of the internal carotid artery
origin
• MCA peak systolic velocity has replaced invasive testing
with amniocentesis for fetal anemia detection
• Fetal hypoxemia → increased blood flow to the brain,
heart and adrenal glands → greater end-diastolic flow
in the MCA AKA “brain sparing”
Ductus Venosus
• First peak reflects ventricular systole
• Second peak is ventricular diastolic filling
• Nadir during atrial contraction – termed the “a wave”
• With severe fetal growth restriction → cardiac
dysfunction may lead to flow in the a-wave that is
decreased, absent and eventually reversed
MAGNETIC RESONANCE IMAGING
• Uses no ionizing radiation
• Generally safe
CHAPTER 11
Amnionic Fluid
Roles of Amniotic Fluid:
• Fetal breathing of amnionic fluid is essential for normal
lung growth
• Fetal swallowing permits GI development
• Physical space for fetal movement (for NM
development)
• Guards against UC compression
• Protects fetus from trauma
• Bacteriostatic properties
NORMAL AMNIONIC FLUID VOLUME
• Increases from approx. 30 mL at 10 weeks to 200ml by
16 weeks and 800 mL by mid-third trimester
31
 • 98% water • Uterus is divided into 4 equal quadrants
• Full term fetus has approx. 2.8L of water + placenta • AFI is the sum of the single deepest pocket from each
(400mL) → total of almost 4L of water quadrant
Physiology: • AFI approximates 3x the single deepest pocket of fluid
• During 1st half of pregnancy – transfer of water takes • 5-25cm
place across the amnion – transmembranous flow,
across the fetal vessels on the placental surface –
intramembranous flow; and across fetal skin –
transcutaneous flow HYDRAMNIOS
• Fetal urine production begins 8-11 weeks AOG but • Abnormally increased AFV
becomes a major component of AF in the 2nd trimester • 1-2% of singleton pregnancies
• Water transport across the fetal skin continues until • Mild: 25-29.9 / SVP 8-9.9
keratinization occurs at 22-25 weeks o Most common
• 4 Pathways that play a major role in AFV regulation: o 2/3 of cases
o Fetal urination – primary source of AF in the • Moderate: 30-34.9
second half of pregnancy o 20% of cases
▪ Fetal urine production by term >1L • Severe: >35 / SVP >12cm
per day o 15%
▪ Osmolality of maternal and fetal ETIOLOGY:
plasma approximates 280mOsm/mL • Structural abnormalities or genetic syndromes – 15%
▪ AF: 260 mOsm/L • Diabetes: 15-20%
o Hypotonicity of the AF accounts for significant • Congenital infection, red blood cell alloimmunization
intramembranous fluid transfer across and and placental chorangioma are less frequent etiologies
into fetal vessels on the placental surface ~
• Infections – CMV, toxoplasmosis, syphilis, parvovirus
reaches 400mL per day
• Often a component of hydrops fetalis
o Respiratory tract – 350m: of lung fluid id
• Related to high cardiac output state (severe fetal
produced daily late in gestation, ½ is
anemia)
swallowed
• Congenital Anomalies:
o Fetal swallowing – primary mechanism for AF
o If fetal abnormality is encountered concurrent
resorption and averages 500-1000mL per day
with hydramnios → amniocentesis with
chromosomal microarray analysis should be
Amnionic Fluid Volume Regulation in Late Pregnancy
offered because aneuploid risk is high
Pathway Effect on Volume Approximate
Daily Volume
(mL) • Diabetes Mellitus:
Fetal urination Production 1000 o Amnionic fluid glucose concentration is higher
Fetal swallowing Resorption 750 in diabetic women
Fetal lung fluid Production 350 o Maternal hyperglycemia → fetal
secretion hyperglycemia → fetal osmotic diuresis
Intramembranous Resorption 400 • Multifetal Gestation:
flow across fetal o Hydramnios in one sac with oligohydramnios
vessels on the in another sac → suggestive of TTTS
placental surface • Idiopathic Hydramnios:
Transmembranous Resorption Minimal o 70% of cases
flow across o Incidental finding later in gestation (32-35
amnionic weeks)
membranes o Mild in approximately 80% of cases and
resolution is reported in more than a third of
Sonographic Assessment: affected pregnancies
• A fluid pocket must be at least 1cm in width to be o Outcomes are usually good
considered adequate o Not associated with preterm birth
• Color doppler to make sure that the UC is not within the
measurements COMPLICATIONS
Single Deepest Pocket • Preterm labor
• Maximal vertical pocket • Dyspnea and orthopnea
• Transducer is held perpendicular to the floor and • Edema as a consequence of major venous system
parallel to the long axis of the woman compression by the enlarged uterus
• The largest vertical pocket of fluid is identified and • Maternal complications associated with hydramnios:
measured o Abruptio
• Normal: 2-8cm (3rd and 97th percentiles) o Uterine dysfunction during labor
Amnionic Fluid Index (AFI) o PPH

32
PREGNANCY OUTCOMES • Estimated percentage of all birth defects caused by
• Birthweight of infant >4000g medications: 1%
• Cesarean delivery
• Perinatal mortality Teratology:
• Study of birth defects and their etiology
MANAGEMENT • Teratogen: medication or other chemical substance,
• Amnioreduction physical or environmental (heat or radiation, maternal
• Gauge 18 or 20 needle metabolite or an infection)
• Approximately 1000-2000mL is slowly withdrawn over o Causes only structural abnormalities
20-30 minutes o Hadegen: agent that interferes with organ
• Goal: restore AF into the normal range maturation and function
o Trophogen: alters growth
OLIGOHYDRAMNIOS • Criteria for Determining Teratogenicity:
• Complicates 1-2% of pregnancies o Essential Criteria:
▪ Careful delineation of clinical cases,
ETIOLOGY: particularly if there is a specific
• Prognosis depends on the underlying cause defect or syndrome
▪ Proof that exposure occurred at
• Early Onset Oligohydramnios
critical time during development
o Fetal abnormality that precludes normal
▪ Consistent findings by at least two
urination
epidemiological studies with:
o Prognosis is poor
• exclusion of bias
• Oligohydramnios after Midpregnancy
o Late second or early third → fetal growth • adjustment for
restriction confounding variables,
o MCC: uteroplacental insufficiency which can • adequate sample size
impair fetal growth and reduce fetal urine (power),
output • prospective ascertainment
• Congenital Anomalies if possible, and
o Renal agenesis • relative risk (RR) of 3.0 or
o Bilateral multicystic dysplastic kidney greater, some recommend
o Unilateral renal agenesis RR of 6.0 or greater
o Autosomal recessive polycystic kidney disease o Ancillary Criteria:
o Fetal bladder outlet obstruction ▪ Association is biologically plausible
• Medication ▪ Teratogenicity in experimental
o Associated with exposure to drugs that block animals is important but not
ACE, ARBs, NSAIDs when taken in the 3rd essential
trimester ▪ Agent acts in an unaltered form in
o Create fetal hypotension, renal hypoperfusion an experimental model
and renal ischemia o Tenets to consider:
▪ Defect has been completely
PREGNANCY OUTCOMES: characterized (preferably by a
• Associated with adverse pregnancy outcomes geneticist or dysmorphologist to
• Fetal malformations were elevated prove causation)
▪ Agent must cross the placenta
• Pulmonary Hypoplasia:
▪ Exposure must occur during a
o If before 20-22 weeks → pulmonary
critical developmental period
hypoplasia is a significant concern
• Preimplantation (2 wks.
MANAGEMENT:
before fertilization ~ “all
• Close fetal surveillance
or none” period)
• If normal fetus, but with oligohydramnios <36 weeks →
• Embryonic period: 2nd-8th
manage expectantly
week post conception –
• Maternal hydration
organogenesis
• Amnioinfusion (not standard of care)
• Fetal period: beyond 8
wks. characterized by
continued maturation
CHAPTER 12 ▪ Biologically plausible association is
supportive
▪ Epidemiological findings must be
Teratology, Teratogens and Fetotoxic consistent
Agents FDA PREGNANCY CATEGORIES:

33
CATEGORY A Studies have not shown an increased risk for
fetal abnormalities
CATEGORY B Animal reproduction have shown no adverse
effect to the fetus or animal studies have
shown an adverse effect but adequate
studies in pregnant women have failed to
demonstrate a risk to the fetus
CATEGORY C Animal reproduction studies have shown it is
teratogenic or no animal reproduction
studies or no adequate well controlled
studies in humans
CATEGORY D Can cause fetal harm; if taken, patient
should be apprised of potential hazard to the
fetus
CATEGORY X Absolutely contraindicated, causes fetal
harm
KNOWN AND SUSPECTED TERATOGENS
ALCOHOL
• Leading cause of preventable developmental disabilities
worldwide
• Fetal alcohol syndrome
• Fetal alcohol spectrum disorder – umbrella term that
includes five conditions attributed to prenatal alcohol
damage:
o Fetal alcohol syndrome
o Partial fetal alcohol syndrome
o Alcohol related birth defects
o Alcohol related neurodevelopmental disorder
o Neurobehavioral disorder
CRITERIA FOR PRENATAL ALCOHOL EXPOSURE, FETAL ALCOHOL
SYNDROME AND ALCOHOL RELATED BIRTH DEFECTS
Documented Prenatal Alcohol Exposure – one or more required
1. > 6drinks per week for >2 weeks
2. > 3drinks per occasion for >2 occasions
3. Risk identified with a validated screening questionnaire
4. Lab test indicating alcohol intoxication
5. Documentation of an alcohol-related legal or social
problem
Fetal Alcohol Syndrome Diagnostic Criteria – all required
1. Dysmorphic facial features (>2 required)
a. Short palpebral fissures
b. Thin vermilion border of upper lip
c. Smooth philtrum
2. Prenatal and/or postnatal growth impairment <10th
percentile
3. Abnormal brain growth, morphogenesis (>1.5 SD below
mean)
a. Child <3 years: developmental delay
b. Child >3 years: global cognitive impairment or
cognitive deficit in at least 1 neurobehavioral
domain or behavioral deficit in at least 1
domain
Alcohol Related Birth Defects
• Cardiac: atrial or ventricular septal defect, aberrant
great vessels
• Skeletal: radioulnar synostosis, vertebral segmentation
defects, joint contractures, scoliosis
• Renal: aplastic or hypoplastic kidneys, dysplastic
kidneys, horseshoe kidney, ureteral duplication
• Eyes: strabismus, ptosis, retinal vascular abnormalities,
optic nerve hypoplasia
• Ears: conductive or neurosensory hearing loss
ANTIEPILEPTIC MEDICATIONS
• Most frequently reported anomalies: orofacial clefts,
cardiac malformation and neural tube defects
• Use of valproic acid confers the greatest risk
• Higher rates among exposed children vs children born
to women with untreated epilepsy
• Risk for fetal malformation is doubled if multiple agents
are required
ACE INHIBITORS AND ARBs
• ACE-inhibitor fetopathy
• Medication may cause fetal hypotension and renal
hypoperfusion with subsequent ischemia and anuria
• Reduced perfusion → FG restriction and calvarium
maldevelopment and oligohydramnios → pulmonary
hypoplasia and limb contractures
ANTIFUNGAL MEDICATIONS
• Fluconazole has been associated with a pattern of
congenital malformations resembling autosomal
recessive Antley-Bixler syndrome
• Oral clefts, abnormal facies and cardiac, long bone and
joint abnormalities
• Tetralogy of fallot after exposure to low dose
fluconazole
ANTIINFLAMMATORY AGENTS
NSAIDs
• Ibuprofen and indomethacin
• Inhibit prostaglandin synthesis
• When taken late in pregnancy, indomethacin may cause
constriction of fetal ductus arteriosus → pulmonary
hypertension
o Esp. if it is taken more than 72 hours
o Decreases fetal urine production an AFV
• Aspirin: low dosage of 100mg daily or less does not
confer a greater risk for constriction of the ductus
arteriosus or for adverse infant outcomes
Leflunomide
• Pyrimidine synthesis inhibitor used to treat RA
• Results in fetal hydrocephalus, eye anomalies, skeletal
abnormalities and embryo death
• Active metabolite teriflunomide is detectable in plasma
for up to 2 years following discontinuation
ANTIMICROBIAL DRUGS
Aminoglycosides
• Streptomycin / gentamicin → nephrotoxicity and
ototoxicity
• No adverse effects have been demonstrated
Chloramphenicol
• Not a teratogenic and no longer routinely used
34
Nitrofurantoin
• Exposure in first trimester is linked to twofold risk for
cleft lip
• First trimester use is appropriate if no suitable
alternatives are available
Sulfonamides
• Used to treat MRSA
• Fivefold greater risk to have offspring with esophageal
atresia or diaphragmatic hernia
• Appropriate for 1st trimester use if suitable alternatives
are lacking
Tetracyclines
• No longer commonly used
• Yellowish brown discoloration of deciduous teeth when
used after 25 weeks AOG
ANTI-NEOPLASTIC AGENTS
Cyclophosphamide (alkylating agent)
• Inflicts a chemical insult on developing fetal tissues and
leads to cell death and heritable DNA alterations in
surviving cells
• Pregnancy loss rates are increased
• Reported malformations: skeletal abnormalities, limb
defects, cleft palate, eye abnormalities
• Environmental exposure among HCW is associated with
a higher risk for spontaneous abortion
Methotrexate (folic acid antagonist)
• Potent teratogen
• Causes craniosynostosis, wide nasal bridge, low set
ears, micrognathia and limb abnormalities
• Embryo most vulnerable at 8-10 weeks and at dosages
of at least 10mg/week
Tamoxifen (non-steroidal selective estrogen receptor
modulator)
• No pattern of birth defects has been described
• Associated with malformations similar to DES exposure
in rodents
Trastuzumab (recombinant monoclonal antibody)
• Directed to the human epidermal growth factor
receptor 2 (HER2) protein
• Not associated with fetal malformations but with
reported cases of oligohydramnios, pulmonary
hypoplasia, renal failure, skeletal abnormalities and
neonatal deaths
ANTI-VIRAL AGENTS
Ribavirin (nucleoside analogue)
• Causes birth defects in multiple animal species at doses
lower than those recommended for human use
• Skull, palate, eye, skeleton and GI abnormalities
• Treated women must use 2 forms of contraception and
have monthly PT while on therapy and for 6 months
after drug discontinuation
• C/I also in men whose partners are pregnant
Efavirenz (nonnucleoside reverse transcriptase inhibitor)
• Used to treat HIV
• Neural tube defects
ENDOTHELIN-RECEPTOR ANTAGONISTS
• Bosentan, ambrisentan, macitentan
• Used to treat pulmonary arterial hypertension
• Endothelin-receptor signaling pathway is important for
neural-crest development
SEX HORMONES
Testosterone and Anabolic Steroids
• Exposure of a female fetus → virilization → ambiguous
genitalia
• Labioscrotal fusion with 1st trimester exposure
Danazol
• Weak androgenic activity
• Used to treat endometriosis, immune
thrombocytopenic purpura, migraine headaches,
premenstrual syndrome and fibrocystic breast disease
• Virilization
• Clitoromegaly, fused labia and urogenital sinus
malformation
Diethylstilbesterol (DES)
• VAGINAL CLEAR CELL ADENOCARCINOMA
IMMUNOSUPPRESSANT MEDICATIONS
Corticosteroids
• Clefts in animal studies
• Prednisone (active metabolite = prednisolone) is
inactivated by placental enzyme 11 beta -
hydroxysteroid DH 2 → will not reach fetus
Mycophenolate Mofetil
• Used to prevent rejection in organ transplant recipient
and to treat autoimmune disease
• Potent teratogen
• Birth defects complicate 30%
• Spontaneous abortion common
• Mycophenolate embryopathy – microtia, auditory canal
atresia, clefts, coloboma and other eye anomalies, short
fingers with hypoplastic nails and cardiac defects
RADIOIODINE
• Radioactive iodine-131 used for treatment of thyroid ca
and thyrotoxicosis and for diagnostic scanning
• Contraindicated because it crosses the placenta and is
concentrated in the fetal thyroid gland by 12 weeks
AOG
• May cause severe or irreversible fetal and neonatal
hypothyroidism → decreased mental capacity and
delayed skeletal maturation
LEAD
• Fetal growth abnormalities with childhood
developmental delay and behavioral abnormalities
MERCURY
• Nervous system
• Developmental delay, microcephaly, brain damage
• Avoid consumption of king mackerel, marlin, orange
roughy, shark, swordfish, tilefish and bigeye tuna
PSYCHIATRIC MEDICATIONS
Lithium
• Ebstein anomaly (cardiac abnormality characterized by
apical displacement of tricuspid valve)
• Neonatal lithium toxicity – exposure near delivery
• Recommendation: dosage should be decreased or
discontinued 2-3 days prior to delivery to reduce the
risk
35
 • Findings persist for 1-2 weeks and include: neonatal • Systemic absorption is low
hypothyroidism, diabetes insipidus, cardiomegaly, Vitamin A
bradycardia, ECG abnormalities, cyanosis, hypotonia • 2 natural forms
SSRI (Selective Serotonin and Norepinephrine Reuptake o Beta carotene: precursor of provitamin A
Inhibitors) (fruits, vegetables) no effect on fetus
• 1.5-two fold greater risk for cardiac malformations o Retinol (preformed vitamin A) → neural crest
following first trimester paroxetine exposure defects if given more than 10,000 IU per day
• Avoid paroxetine in women planning pregnancy in the 1st trimester
• Fetal echo is a must • Avoid doses of preformed preparations that exceed the
• If in late pregnancy → poor neonatal adaptation recommended 3000 IU daily allowance
o “Neonatal behavioral syndrome” →
jitteriness, irritability, hyper or hypotonia,
feeding abnormalities, vomiting,
hypoglycemia, thermoregulatory instability THALIDOMIDE AND LENALIDOMIDE
and respiratory abnormalities • Most notorious human teratogen
o Sx last for 2 days • Used to treat erythema leprosum nodusum and
o Persistent pulmonary hypertension of the multiple myeloma
newborn (PPHN) • Phocomelia – absence of one or more long bones
▪ Pulmonary vascular resistance with • Cardiac malformations, GI abnormalities, external ear
right to left shunting and resultant malformations, eye anomalies and other limb reduction
hypoxemia defects
Antipsychotic Medications • Exposure during days 24-30 post conception: upper
• NONE are considered teratogenic limb amelia
• Exposure during 24-33: upper limb phocomelia
RETINOIDS • Exposure days 27-33: lower limb phocomelia
• Vitamin A derivatives WARFARIN
• Most potent human teratogens • Anticoagulant – vitamin K antagonist with long half life
• When orally administered – isotretinoin, acitretin and • Low molecular weight → crosses the placenta and
bexarotene cause embryotoxic and fetotoxic effects
• Inhibits neural crest cell migration during • Warfarin embryopathy – stippled epiphysis and nasal
embryogenesis → cranial neural crest defects “retinoic hypoplasia
acid embryopathy” that involve CNS, face, heart and • Exposure between 6-9 weeks AOG
thymus • Risk may be dose dependent
• Ventriculomegaly, maldevelopment of facial bones or • If used beyond 1st trimester → fetal hemorrhage →
cranium, microtia or anotia, micrognathia, cleft palate, abnormal growth and deformation from scarring
conotruncal heart defects and thymic aplasia or • Can cause agenesis of corpus callosum, cerebellar
hypoplasia vermian agenesis (Dandy Walker malformation)
microphthalmia and optic atrophy
Isotretinoin • Risk for blindness, deafness and developmental delays
• 13-cis retinoic acid HERBAL REMEDIES
• Vitamin A isomer • Safety data are generally limited
• Stimulates epithelial cell differentiation HERB EFFECT CONCERNS
• Used for cystic nodular acne Aloe SM stimulant Uterine contractions
• First trimester exposure → high rate of pregnancy loss Black cohosh SM simulant UC, estrogenic compound
and 1/3 of fetuses who survive have malformations Blue cohosh SM stimulant UC, compounds teratogenic in
multiple animal species
Acitretin Echinacea; Activates cell Allergic reactions, deceases
• Used for severe psoriasis purple mediated immunosuppressant effectiveness;
• Delay in conception for at least 3 YEARS AFTER coneflower root immunity immunosuppression
discontinuation Ephedra: ma Direct and indirect HPN, arrythmias, MI, stroke,
Bexarotene huang sympathomimetic, depletes endogenous
tachycardia, HPN catecholamines, life threatening
• Used to treat cutaneous T-cell lymphoma interaction with monoamine oxidase
• Eye and ear abnormalities inhibitors
• Manufacturer requires 2 forms of contraception Evening Linoleic acids and Possible complications if used for
initiated 1 month before therapy and continued for 1 primrose oil prostaglandin labor induction
precursor
month after discontinuation
Garlic ajo Inhibits platelet Risk of bleeding esp. when
• Males who have partners who could become pregnant aggregation, combined with other platelet
are advised to use condoms while taking bexarotene increased aggregation inhibitors
and for 1 month after discontinuing therapy fibrinolysis, anti-
Topical Retinoids HPN
Ginger Cyclooxygenase Increased risk of bleeding
• Cosmeceuticals
inhibitor,
• Most commonly used – tretinoin, isotretinoin, thromboxane
adapalene
36
 synthetase
inhibitor CHAPTER 13
Ginkgo biloba Anticoagulant Risk of bleeding, interferes with
MOA inhibitors
Ginseng Lowers blood Hypoglycemia, hypertension, risk of Genetics
glucose, inhibits bleeding • Genetics: study of genes, heredity and variation of
platelet
aggregation
inherited characteristics
Kava: awa, Sedation, Sedation; tolerance, withdrawal • Medical genetics: etiology and pathogenesis of human
intoxicating anxiolysis diseases that are at least partially genetic in origin along
pepper, kawa with their prediction and prevention
Valerian: all Sedation Sedation, hepatotoxicity, o Includes: prenatal and preimplantation
heal, garden benzodiazepine like acute
genetic diagnosis and newborn genetic
heliotrope, withdrawal
vandal root screening
Yohimbe Hypertension, arrythmias • Genomics: study of gene function and interaction

RECREATIONAL DRUGS CHROMOSOMAL ABNORMALITIES

• Alcohol – a significant teratogen
Amphetamines
• SGA newborns
Cocaine
• Vasoconstrictive and hypertensive effects
• Cerebrovascular hemorrhage, myocardial damage and
placental abruption
Opioids-Narcotics
• Heroin associated with adverse pregnancy outcomes
from the effects of repeated narcotic withdrawal on the
fetus and placenta
• Neonatal narcotic withdrawal termed “neonatal
abstinence syndrome”
o Tachypnea, apneic episodes, poor feeding and
failure to thrive
Marijuana
• MOST COMMONLY USED IN PREGNANCY
• Endogenous cannabinoids play key roles in human brain
development
• Preterm birth and low BW are common
Miscellaneous Drugs
• Phencyclidine (PCP) or angel dust: not associated with
congenital anomalies but newborns experience
withdrawal symptoms (tremors, jitteriness and
irritability)
• Toluene – used in paints and glue → occasional reports
of fetal risks
o Toluene embryopathy – similar to fetal
alcohol syndrome
o Pre and postnatal growth deficiency,
microcephaly, midface hypoplasia, short
palpebral fissures and wide nasal bridge
TOBACCO
• Vasoactive effects or reduce oxygen levels
• Association with hydrocephaly, microcephaly,
omphalocele, gastroschisis, cleft lip and palate and
hand abnormalities
• Electronic nicotine – adverse effects on fetal brain and
lung development
• Reduction in fetal growth
• Secondhand smoke – increased risk for low birthweight
infants
• Preterm birth, placenta previa, abruptio, spontaneous
abortion and SIDS
• Aneuploidy accounts for more than 50% of 1st trimester
miscarriages and 20% of second trimester losses, 6-8%
of stillbirths and early childhood deaths
• Trisomy 21 composes more than half of all cases
• Trisomy 18 accounts for 15%
• Trisomy 13 – 5%
ABNORMALITIES OF CHROMOSOME NUMBER
• Most easily recognized chromosomal abnormalities are
numerical
• Aneuploidy: inheritance of either an extra chromosome
(trisomy) or loss of a chromosome (monosomy)
• Polyploidy: abnormal number of haploid chromosome
sets (triploidy)
Autosomal Trisomies
• Account for half of all chromosomal abnormalities
• Results from nondisjunction – failure of normal
chromosomal pairing and separation during meiosis
• Nondisjunction may occur if the chromosomes:
o Fail to pair up
o Pair up properly but separate prematurely
o Fail to separate
• Nondisjunction results in one gamete having 2 copies of
the affected chromosome leading to trisomy if fertilized
• The other gamete, receiving no copy of the affected
chromosome will be monosomic if fertilized
• 10-20% of oocytes are aneuploid secondary to meiotic
errors compared with 3-4% of sperm
• After a pregnancy with an autosomal trisomy – risk for
any autosomal trisomy in future pregnancy
approximates 1% until the woman’s age related risk
exceeds this
Trisomy 21 – Down Syndrome
• Causes 95% of down syndrome
• Occurs during meiosis I
• Most common nonlethal trisomy
• Prevalence has increased 33% due to AMA
• Males with Down Syndrome are ALMOST ALWAYS
sterile because of markedly reduced spermatogenesis
• When both major anomalies and minor aneuploidy
markers are considered, an estimated 50-60% are
diagnosed sonographically
• 50% are found to have cardiac defects – VSD,
endocardial cushion defects

37
 • GI – 12% (esophageal atresia, Hirschsprung, duodenal
atresia)
• Hearing loss in 75%
• Severe optical refractive errors in 50%, cataracts in 15%
• Obstructive sleep apnea – 60%
• Thyroid disease 15%
• Higher incidence of leukemia
Trisomy 18 – Edwards Syndrome
• 1 YR SURVIVAL IS ONLY 2%
• Robertsonian translocation
• Chromosomal rearrangement
• Heart defects in more than 90% - VSD, cerebellar
vermian agenesis, myelomeningocele, diaphragmatic
hernia, omphalocele, imperforate anus and renal
anomalies
• Strawberry shaped cranium in 4% of cases
• Mean BW: <2500 g
Trisomy 13 – Patau Syndrome
• HIGHLY LETHAL
• Most affected fetuses are lost or terminated
• Translocation between chromosome 13 and 14
• Associated with abnormalities of virtually every organ
system
• Cardiac defects in 90%
• Neural tube defects – cephalocele, microphthalmia,
cleft lip-palate, omphalocele, cystic renal dysplasia,
polydactyly, rocker bottom feet and areas of skin
aplasia
• 1 week survival is 40%, 1 year survival: 3%
• Hyperplacentosis and pre-ec develop in up to half of
pregnancies carried beyond the 2nd trimester
• Chromosome 13 contains the gene for soluble fms-like
tyrosine kinase 1 (antiangiogenic protein asso with
preeclampsia)
Monosomy
• Nondisjunction creates equal number of nullisomic and
disomic gametes
• One exception is monosomy for the X chromosome (45,
X – Turner Syndrome)
• Maternal age and monosomy are not linked!
Polyploidy
• Abnormal number of complete haploid chromosomal
sets
• 20% of SAB but rare in later gestations
• Triploid have 3 haploid sets – 69 chromosomes
• Diandirc triploidy – type I triploidy, the extra
chromosomal set is paternal resulting from fertilization
of one egg by 2 sperms or by a single diploid and thus
• abnormal sperm
o Produces partial molar pregnancy
• Digynic triploidy – type II triploidy
o Extra chromosomal set is maternal, and egg
fails to undergo the 1st or 2nd meiotic division
before fertilization
• Recurrence for triploidy in a woman whose triploid
fetus survived past the first trimester is 1-1.5%
• Tetraploid pregnancies – 4 haploid sets of
chromosomes → 92, XXXX or 92, XXXY
o Post zygotic failure to complete an early
cleavage division
Sex Chromosome Abnormalities
45, X – Turner Syndrome
• Monosomy X
• 1 in 2500 liveborn girls
• Missing X chromosome is paternally derived in 80%
• Only monosomy compatible with life
• Most common aneuploidy in 1 st trimester losses (20%)
• 90% abort during the first trimester, of the remainder,
many manifest large, septated cystic hygromas in the
late first or early second trimester
• If accompanied by hydrops – fetus nearly always diet in
utero
• Less than 1% yield a liveborn neonate
• Anomalies: left sided cardiac defects – CoA, hypoplastic
left heart syndrome, bicuspid aortic valve, renal
anomalies (horseshoe kidney) and hypothyroidism
• Others: short stature, broad chest, widely spaced
nipples, congenital lymphedema – puffiness over
dorsum of hands and feet and a “webbed” posterior
neck resulting from cystic hygromas
• Growth hormone in childhood may be given to
ameliorate short stature
• 90% have ovarian dysgenesis and require estrogen
repletion just before adolescence
• Risk for germ cell neoplasm
47, XXX
• Extra X is maternally derived in more than 90% of cases
• Tall stature, hypertelorism, epicanthal folds,
kyphoscoliosis, clinodactyly and hypotonia
• Learning disabilities, ADD and overall cognitive scores
are in the low-average range
• Genitourinary and seizure problems are more common
47, XXY – Klinefelter Syndrome
• Most common sex chromosome abnormality
• Additional X chromosome is maternally or paternally
derived
• Gonadal dysgenesis and do not undergo normal
virilization → require testosterone supplementation
beginning in adolescence
47, XYY
• 1 in 1000 male newborns
• Boys tend to be tall
• Pubertal development is normal, fertility is unimpaired
• Risk for oral and written language impairments, ADD is
diagnosed in more than half
Abnormalities of Chromosome Structure
• Deletions, duplications, translocations,
isochromosomes, inversions, ring chromosomes and
mosaicism
• Overall birth prevalence is -.3%
Deletions and Duplications
• Occur during meiosis and result from malalignment or
mismatching during the pairing of homologous
chromosomes
• Parental karyotyping
38
 • Cri-du-chat syndrome
Microdeletions and Microduplications
• Smaller than 3-5 million base pairs
• Prenatal chromosomal microarray analysis (CMA)
permits detection
22q11.2 Microdeletion Syndrome
• DiGeorge syndrome, Shprintzen syndrome and
velocardiofacial syndrome
• Most common microdeletion
• 90% arise from de novo mutations
• Tetralogy of fallot, truncus arteriosus, interrupted aortic
arch and VSD
• Learning disabilities, ASD and intellectual disability are
also common
Chromosomal Translocations
• Segment of DNA breaks away from one chromosome
and attaches to another
Reciprocal Translocations:
• Breaks occur in 2 different chromosomes → broken
fragments are exchanged → each affected chromosome
contains a fragment of the other
• Balanced if no chromosomal material is gained or lost
Robertsonian Translocations:
• Acrocentric chromosomes – 13, 14, 15, 21 and 22
• Extremely short p arms
• Carrier has only 45 chromosomes
• Incidence of abnormal offspring is approx. 15% if
carried by the mother and 2% if carried by the father
Isochromosomes
• Composed of either 2 q arms or 2 p arms of one
chromosome fused together
• When centromere breaks traversely instead of
longitudinally during meiosis II or mitosis
Chromosomal Inversions
• When there are 2 breaks in the same chromosome and
intervening, genetic material is inverted before the
breaks are repaired
Pericentric inversion:
• Breaks in both he p and q arms → inverted material
includes the centromere
• Causes problems in chromosomal alignment during
meiosis and confers significant risk for the carrier to
produce abnormal gametes and offspring
• Chromosome 9 pericentric inversion is a normal variant
Paracentric inversion:
• 2 breaks within one arm of a chromosome (either p or
q) the inverted material does not include the
centromere
Ring Chromosome
• If there are deletions at each end of the same
chromosome
Chromosomal Mosaicism
• Has 2 or more cytogenetically distinct cell lines that are
derived from a single zygote
• Pseudomosaicism – caused by cell culture artifact (if the
mosaicism is seen in a single flask of AF)
Confined Placental Mosaicism
• Fetal growth restriction is more common
o May stem from impaired functioning of the
aneuploid placental cells
Gonadal Mosaicism
• Confined to the gonads
• Arises from a mitotic error in cells destined to become
the gonad → population of abnormal germ cells
• Autosomal dominant examples: achondroplasia and
osteogenesis imperfecta
• X linked ones: Duchenne muscular dystrophy
MODES OF INHERITANCE
Mendelian Disorder: caused by a mutation or alteration in a
single locus or gene in one or both members of a gene pair
• Autosomal dominant
• Autosomal recessive
• X linked
• Y linked
Relationship between Phenotype and Genotype
• When considering inheritance, it is the phenotype that
is dominant or recessive (not the genotype)
• Heterogenicity
o Explains how different genetic mechanisms
can result in the same phenotype
o Locus heterogeneity: a specific disease
phenotype can be caused by mutations in
different genetic loci
o Allelic heterogeneity: how different
mutations of the same gene may affect
presentation of a particular disease
o Phenotypic heterogeneity: explains how
different diseases states can arise from
different mutations in the same gene
AUTOSOMAL DOMINANT INHERITANCE
• If only one copy of a gene determines the phenotype,
that gene is considered to be more dominant
• 50% chance of passing the affected gene with each
conception
• Penetrance: whether or not a dominant gene is
expressed at all
o A gene with recognizable phenotypic
expression in all individuals is 100% penetrant
o Incomplete if some carriers express the gene
but some do not
o “skip generations”
• Expressivity: individuals with the same autosomal
dominant trait may manifest differently even within the
same family
• Codominant Genes: if 2 different alleles in a gene pair
are both expressed in the phenotype
o Blood type is determined by expression of
dominant A and B red cell antigens
o An individual with one gene directing
production of hemoglobin S and other
directing production of hemoglobin C will
produce both S and C hemoglobin
• Advanced Paternal Age
39
 o Fathers older than 40 is associated with
increased risk for spontaneous genetic
mutations
o Advanced paternal age has been associated
with mutations in the fibroblast growth factor
receptor 2 (FGFR2) → craniosynostosis such
as Apert, Crouzon and Pfeiffer syndromes
o Greater risk for fetal Down syndrome
AUTOSOMAL RECESSIVE INHERITANCE
• Only develop when both gene copies are abnormal
• Usually are recognized only after birth of an affected
child
• Recurrence risk if 25% for each subsequent pregnancy,
¼ will be homozygous normal, 2/4 will be heterozygous
carriers and ¼ will be homozygous abnormal (3 of 4
children will be phenotypically normal and 2/3 of
phenotypically normal siblings are carriers)
Inborn Errors of Metabolism
• Absence of a crucial enzyme → incomplete metabolism
of proteins, lipids or carbohydrates
• Phenylketonuria: phenylalanine hydroxylase (PAH)
deficiency
o Mutations in the PAH gene
o PAH metabolizes phenylalanine → tyrosine
o Results in progressive intellectual impairment,
autism, seizures, motor deficits and
neuropsychological abnormalities
o Phenylalanine competitively inhibits tyrosine
hydroxylase (essential for melanin
production) → hair, eye and skin
hypopigmentation
o Restriction of phenylalanine beginning early in
infancy are essential to prevent neurological
damage
o Phenylalanine free amino acid based
supplementation is required
o Lifelong maintenance of phenylalanine
concentrations in the range of 2-6 mg/dl is
necessary to prevent worsening
neurocognitive and psychiatric problems
• Consanguinity
o If 2 individuals have at least one recent
ancestor in common
o First cousins are reported to have a 2fold risk
for congenital anomalies
o Greater rate of stillbirth
o Pregnancy between incestuous relationships
carry the highest risk of abnormal outcomes
X LINKED AND Y LINKED INHERITANCE
• Most X linked are recessive (color blindness, hemophilia
A and B, Duchenne and Becker muscular dystrophy)
• Males are usually affected because they lack a second X
chromosome to express the normal dominant gene
• A man will not have affected sons because they cannot
receive his X chromosome
• A woman who is a carrier, each of her sons has a 50%
risk of being affected and each daughter has a 50% risk
of being a carrier
• X linked dominant disorders mainly affect females
because they are lethal in males
o Examples: Vitamin D resistant rickets and
incontinentia pigmenti
• Prevalence of Y linked disorders is low
o Carries genes important for sex determination
and cellular functions related to
spermatogenesis and bone development
MITOCHONDIRAL INHERITANCE
• Mitochondria are inherited exclusively from the mother
→ transmission is only thought the mother
DNA TRIPLET REPEAT EXPANSION-ANTICIPATION
• Anticipation: disease symptoms seem to be more
severe and appear at an earlier age in each successive
generation
• Fragile X Syndrome: most common inherited form of
intellectual disability and affects 1 in 3600 males and 1
in 4000-6000 females
o Caused by expansion of a repeated
trinucleotide DNA segment – CGG at
chromosome Xq27.3
o When the CGG repeat number reaches a
critical size the fragile X mental retardation 1
(FMR1) gene becomes methylated →
inactivation of the gene → FMR1 protein is
halted (protein needed for nerve cells and
essential for normal cognitive development)
o Intellectual disability more severe in males
o Most common cause of autism or “autistic
like” behavior
o 4 Groups:
▪ Full mutation: >200 repeats
▪ Premutation: 55-200 repeats
▪ Intermediate: 45-54 repeats
▪ Unaffected: <45 repeats
IMPRINTING
• Genes that are inherited but not expressed
• Resulting phenotype varies according to the parent of
origin
• Affects gene expression by epigenetic control which
modifies genetic structure
• Prader Willi Syndrome: obesity, hyperphagia, short
stature, small hands, feet and external genitalia, mild
mental retardation
o Caused by microdeletion or disruption for the
paternal 15q11.2-q13
• Angelman syndrome: severe intellectual disability,
normal stature and weight, absent speech, seizures
disorder, ataxia and jerky arm movement, paroxysms of
inappropriate laughter
o Microdeletion of maternal 15q11.2-q13
• Complete H.mole with a paternally derived diploid
chromosomal complement is characterized by
abundant placental growth with no fetal structures
• Ovarian teratoma – maternally derived diploid
chromosomal complement
UNIPARENTAL DISOMY
• When both members of a chromosome pair are
inherited from the same parent
40
 • Isodisomy: individual receives 2 identical copies of one
chromosome in a pair from one parent
MULTIFACTORIAL INHERITANCE
• Traits or diseases are considered to have multifactorial
inheritance if they are determined by the combination
of multiple genes and environmental factors
Threshold Traits
• Some multifactorial traits do not appear until a
threshold is exceeded
Cardiac Defects
• Structural cardiac anomalies are the most common
birth defects with a prevalence of 8 cases per 1000
• Risk of having a child with a cardiac anomaly is 5-6% if
the mother has it and 2-3% if the father has it
Neural Tube Defects
• May be influenced by hyperthermia, hyperglycemia,
teratogen exposure, ethnicity, family history, fetal
gender and various genes
• Hyperthermia linked with anencephaly risk
• Pregestational diabetes linked with cranial and cervical
thoracic defects
• Valproic acid – lumbosacral defects
• Recurrence risk of 3-5% is decreased by at least 70-95%
with folic acid supplementation of 4mg/day
GENETIC TESTS
• Most commonly used tests: cytogenetic analysis
(karyotyping), fluorescence in situ hybridization (FISH)
and chromosomal microarray analysis
CYTOGENETIC ANALYSIS
• Karyotype analysis
• Detects numerical abnormalities – aneuploidy
• Dividing cells are arrested in metaphase and
chromosomes are stained to reveal light and dark bands
• Giemsa staining – most common
• AF, GI mucosal cells and amniocytes – results 7-10 days
• Fetal blood cells provide results in 36-48 hrs.
FLUORESCENCE IN SITU HYBRIDIZATION (FISH)
• Rapid identification of a specific chromosome
abnormality and for verification of suspected
microdeletion or duplication syndromes
• Often selected for cases in which findings may alter
pregnancy management (because fast results)
• Cells are fixed into a glass slide
• Most common prenatal use involves testing interphase
chromosomes with DNA sequences specific to
chromosomes 21, 18, 13, X and Y
CHROMOSOMAL MICROARRAY ANALYSIS (CMA)
• 100x more sensitive than standard karyotyping and
detects microduplications and microdeletions as small
as 50-100 kilobases
• Results in 3-5 days
• Detect aneuploidy, unbalanced translocations and
microdeletions and microduplications
• Couples with recurrent pregnancy loss should be
offered karyotyping as the first line test
Clinical Applications:
• In pregnancies at increased risk for autosomal trisomy
based on aneuploidy screening, karyotyping or FISH
plus karyotyping should be offered and CMA should be
made available
• CMA offered as a first tier test when fetal structural
abnormalities are identified
• For stillbirth evaluation → CMA
WHOLE GENOME SEQUENCING AND WHOLE EXOME
SEQUENCING
• Technique for analyzing the entire genome
• If CMA has failed to reach a diagnosis
• Only for recurrent lethal anomalies
FETAL DNA IN THE MATERNAL CIRCULATION
• Fetal cells are in maternal blood at very low
concentrations (2-6 cells/ml)
• Microchimerism – persistent fetal cells engrafted in the
mother → has been implicated in maternal
autoimmune diseases (scleroderma, SLE, hashimoto)
Cell Free DNA
• DNA fragments derived from maternal cells and from
apoplectic placental trophoblast cells
• Can be detected in maternal blood after 9-10 weeks
gestation
• Cell free DNA is cleared from maternal blood within
minutes (unlike intact fetal cells)
• Used to detect paternally inherited alleles (myotonic
dystrophy, achondroplasia, Huntington, CAH, cystic
fibrosis, alpha thalassemia)
Fetal Sex Determination
• If fetus is at risk for an X-linked disorder
Rh Genotype Evaluation
• Early detection of an Rh D-negative fetus might avoid
unnecessary middle cerebral artery Doppler assessment
or amniocentesis
CHAPTER 14
Prenatal Diagnosis
GOAL: to provide accurate information regarding short and long
term prognosis, recurrence risk and potential therapy thereby
improving patient counselling and optimizing outcomes
• Overall sensitivity for amniocentesis to diagnose open
neural tube defects is approx. 98%
• Targeted sonography is the diagnostic test of choice for
neural tube defects
FIRST TRIMESTER ANEUPLOIDY SCREENING
• Combines two maternal serum analytes – hCG and
pregnancy associated plasma protein A (PAPP-A) with
sonographic measurement of NT
• Performed between 11-14 weeks AOG
• Trisomy 21: hCG is high, PAPP-A is low
• Trisomy 18 and 13: levels are both low
Nuchal Translucency:
41
 • Maximum thickness of the SC translucent area between • Nasal bone absence or hypoplasia
the skin and soft tissue overlying the fetal spine at the • Nuchal fold thickening
back of the neck • Renal pelvis dilation (mild)
• If > 3mm → aneuploidy risk is high • Sandal gap between first and second toes
• Detects approximately 2/3 of fetuses with Down • Shortened ear length
syndrome • Single transverse palmar crease
• Single umbilical artery
SECOND TRIMESTER ANEUPLOIDY SCREENING • Short femur
QUADRUPLE MARKER OR “QUAD” SCREENING TEST • Short humerus
• Performed 15-21 weeks AOG • Widened iliac angle
• Down Syndrome: (HI – Hcg, Inhibin) THALASSEMIAS
o Low maternal serum AFP • Most common single gene disorders worldwide and up
o High hCG to 200 million people carry a gene for one of these
o Lower unconjugated estriol hemoglobinopathies
o High Dimeric Inhibin Alpha Thalassemia
• Trisomy 18: low everything (inhibin not part of • Number of alpha globin genes that are deleted may
screening) range from 1 to 4
MATERNAL SERUM AFP ELEVATION: NEURAL TUBE DEFECT • Alpha thalassemia trait is common among African,
SCREENING Mediterranean, Middle Eastern, West Indian and SE
• Offered to all pregnant women Asian descent → mild anemia
• Between 15-20 weeks as part of routine prenatal care • When both parents carry cis deletions, offspring are at
LOW MATERNAL SERUM ESTRIOL LEVEL risk for an absence of alpha hemoglobin called Hb Barts
• If less than 0.25 MoM is associated with disease → hydrops and fetal loss
o Smith-Lemli-Ipitz syndrome (autosomal Beta Thalassemia
recessive) • Mutations in beta globin genes may cause reduced or
▪ Abnormalities in CNS, heart, kidney absent production of beta globin chains
and extremities with ambiguous • If mutation affects 1 gene → Beta thal minor
genitalia and fetal growth • If both copies are affected → Beta thal major / Cooley
restriction anemia or B thal intermedia
▪ Perform sonographic evaluation • Beta thal minor is more common in Africa,
o Steroid sulfatase deficiency / X linked Mediterranean and SEA descent
ichthyosis TAY SACHS DISEASE
▪ Asso with Kallman syndrome, • Screening should be offered before pregnancy if both
chondrodysplasia punctata and/or members of a couple are of Ashkenazi Jewish, French-
mental retardation Canadian or Cajun descent or if there is a family history
SONOGRAPHIC SCREENING of Tay-Sachs disease
“Soft signs” OTHER RECESSIVE DISEASES IN ASHKENAZI JEWS
• Nuchal skinfold: measured in the transcerebellar view • Canavan disease
of the fetal head from outer edge of the skull to the • Familial dysautonomia
outer border of the skin • Bloom syndrome
o Measurement: >6mm is abnormal
• Familial hyperinsulinism
• Echogenic cardiac focus: focal papillary muscle
• Fanconi anemia
calcification that is neither a structural nor functional
• Gaucher disease
cardiac abnormality and is usually left sided
• Glycogens storage disease type I (von Gierke disease)
o An isolated finding doubles the risk for fetal
• Joubert syndrome
Down syndrome
• Maple syrup urine disease
• Mild renal pelvis dilatation: usually transient or
physiological and does not present an underlying • Muclolipidosis type IV
abnormality • Niemann-Pick disease
• Echogenic fetal bowel: bowel that appears as bright as • Usher syndrome
fetal bone
o Represents: small amounts of swallowed PRENATAL DIAGNOSTIC PROCEDURES AND PREIMPLANTATION
blood TESTING
o Risk for: down syndrome 6fold Amniocentesis:
o Also associated with cystic fibrosis, fetal CMV • Most common prenatal diagnostic procedure
infection • Transabdominal withdrawal of AF between 15-20 weeks
• Aberrant right subclavian artery but may be performed at any point later in gestation
• Brachycephaly or shortened frontal lobe • Diagnosis of fetal genetic disorders, congenital
• Clinodactyly (hypoplasia of the 5th digit middle phalanx) infections, alloimmunization, assessment of fetal lung
• Echogenic bowel maturity
• Flat facies • CMA, FISH
• Echogenic intracardiac focus
42
 • Uses a 20 or 22 gauge spinal needle and ultrasound
guidance
• The amnion fuses with the adjacent chorion by 16
weeks AOG hence procedure is deferred until after
chorioamnion fusion has occurred
• AF should be clear and colorless or pale yellow
• Discard 1-2 ml of fluid aspirate during the first
aspiration because it contains maternal cells
• 20-30ml is collected for fetal CMA or karyotyping
• If Rh D negative and unsensitized, anti-D Ig is
administered following the procedure
TEST VOLUME
Fetal karyotype 20ml
CMA 20ml
FISH 10ml
Alpha fetoprotein 2ml
PCR for CMV, toxoplasmosis or parvovirus 1-2ml each
CMV culture 2-3ml
Delta OD 450 (bilirubin analysis) 2-3ml
Genotype studies (alloimmunization) 20ml
Fetal lung maturity 10ml
• Complications: 12% of fetal deaths associated with
preexisting intrauterine infection
o Amniotic fluid leakage (happens within 48 hrs.
after procedure, fetal survival is 90%
o Transient vaginal spotting (1-2%)
• Early Amniocentesis: performed between 11-14 weeks
o Challenging due to lack of membrane fusion
to the uterine wall
o Higher rate of procedure-related
complications (clubfoot, AF leakage and fetal
loss)
o NOT RECOMMENDED
Chorionic Villus Sampling
• Between 10-13 weeks AOG
• Results are available earlier in pregnancy → more time
for decision making and safer pregnancy termination
• May be obtained transcervically or transabdominally
• Sonography is used as guide to guide catheter or needle
into the early placenta – chorion frondosum followed
by aspiration of villi into a syringe
• Relative contraindications:
o Vaginal bleeding / spotting
o Active genital tract infection
o Extreme uterine ante or retroflexion
• Complications:
o Overall loss rate is higher than following
midtrimester amniocentesis
o Associated with limb reduction defects and
oromandibular limb hypogenesis – usually in
procedures performed at 7 weeks
Fetal Blood Sampling / Cordocentesis or Percutaneous Umbilical
Blood Sampling (PUBS)
• Fetal anemia assessment – most common indication
• 22 or 23 gauge spinal needle into the umbilical vein and
blood is slowly withdrawn into a heparinized syringe
• Performed near the placental cord insertion site where
it is easier to enter
• Complications:
o 1.4% fetal loss
o Cord vessel bleeding in 20-30% of cases
o Fetal maternal bleeding in 40% in which
placenta is traversed
o Fetal bradycardia 5-10%
Preimplantation Genetic Testing
• For couples undergoing IVF
• Preimplantation Genetic Diagnosis (PGD)
o To determine if an oocyte or embryo has the
defect
o Only embryos without that abnormality will
be implanted
• Preimplantation Genetic Screening (PGS)
o Used for aneuploid screening that is
performed on oocytes or embryos before IVF
transfer
o Used with couples who are not known to have
or carry a genetic abnormality
• Polar body analysis: to infer whether a developing
oocyte is affected by a maternally inherited genetic
disorder
• Blastomere biopsy done at the 6-8 cell (cleavage) stage
when an embryo is 3 days old and allows both maternal
and paternal genomes to be evaluated
• Trophectoderm biopsy: removal of 5-7 cells from a 5-6
day blastocyst
o Advantage: because the trophoectoderm
cells give rise to the trophoblast – the
placenta – no cells are removed from the
developing embryo
o Disadvantage: procedure is performed later
in development
Preimplantation Genetic Diagnosis
• To determine if an oocyte or embryo has the defect
• Only embryos without the abnormality will be
implanted
CHAPTER 15
Fetal Disorders
FETAL ANEMIA
• Most frequent cause: red cell alloimmunization which
results from transplacental passage of maternal
antibodies that destroy fetal red cells
• Leads to overproduction of immature fetal and
neonatal red cells – erythroblastosis fetalis AKA
hemolytic disease of the fetus and newborn
• Associated with parvovirus B19
• Progressive fetal anemia from any cause → heart
failure, hydrops fetalis and death
RED CELL ALLOIMMUNIZATION
• Any individual who lacks a specific red cell antigen may
produce an antibody when exposed to that antigen
• A fetus inherits at least one red cell antigen from the
father that is lacking in the mother → mother may
become sensitized if enough fetal erythrocytes reach
her circulation → immune response
• 1% of pregnancies
• Most cases of severe fetal anemia requiring antenatal
transfusion are attributable to anti-D and anti-Kell, anti-
c or anti-E alloimmunization
43
• Alloimmunization Detection:
o Blood type and antibody screen are assessed
o Indirect coombs test → if positive → identify
specific antibodies and Ig subtype is
determined as either IgG or IgM and the titer
is quantified
• CDE (Rh) Blood Group Incompatibility
o Includes 5 red cell proteins or antigens: C,c D,
E and e
o No “d” antigen and D-negativity is the
absence of the D antigen
o D negative individuals may become sensitized
after a single exposure to as little as0.1ml of
fetal erythrocytes
o RHD and RHCE located in short arm of ©1
o Without anti-D Ig prophylaxis, a D-negative
woman delivered of a D-positive ABO-
compatible newborn has a 16% likelihood of
developing alloimmunization
▪ 2& sensitized by time of delivery
▪ 7% by 6 months postpartum
o If there is ABO incompatibility, the D
alloimmunization risk approximates 2%
without prophylaxis
• The Grandmother Effect
o Small amounts of maternal blood enter the
fetal circulation
o Possible for a D-negative female fetus
exposed to maternal D-positive red cells to
develop sensitization → when she reaches
adulthood, she may produce anti-D
antibodies even before or early in her first
pregnancy
• Alloimmunization to Minor Antigens:
o More cases of hemolytic disease are caused
by red cell antigens other than D
o Kell antigens are among the most frequent
• Kell Alloimmunization:
o Not routinely determined
o 90% of Kell sensitization result from
transfusion with Kell positive blood
o Kell antibodies attach to erythrocyte
precursors in the fetal bone marrow →
impairment of normal hemopoietic response
to anemia
• ABO blood group incompatibility
o Most common cause of hemolytic disease in
newborns but it does not cause appreciable
hemolysis in the fetus
o 20% of fetuses have ABO incompatibility yet
only 5% are affected clinically
o Often seen in firstborn neonates
o Most group O women have developed anti-A
and anti-B isoagglutinins before pregnancy
from exposure to bacteria
o ABO alloimmunization rarely becomes more
severe in successive pregnancies
o Considered a pediatric disease – rarely of
obstetric concern
MANAGEMENT OF ALLOIMMUNIZED PREGNANCY
• 25-30% of fetuses from D-alloimmunized pregnancies
will have mild to moderate hemolytic anemia
Determining Fetal Risk
• Up to 40% of D-negative pregnant women carry a D-
negative fetus
• If father is negative for the red cell antigen to which the
mother is sensitized = pregnancy is not at risk
• If father is D-positive → alloimmunization occurs
• Use cell free DNA from maternal plasma
• MCA Doppler Velocimetry:
o Serial measurement of the peak systolic
velocity of the fetal MCA is the recommended
test for detection of fetal anemia
Fetal Blood Transfusion
• Fetal blood sampling and intrauterine transfusion are
performed prior to 34-35 weeks
• Recommended ONLY IF THE FETAL HEMATOCRIT IS
<30%
PREVENTION OF ANTI-D ALLOIMMUNIZATION
• Routine postpartum administration of anti-D immune
globulin to at-risk pregnancies within 72 hours of
delivery lower the alloimmunization rate by 90%
• Formulations prepared by cold ethanol fractionation
and ultrafiltrate must be administered IM (do not give
IV as it contains plasma proteins that can result to
anaphylaxis)
• If formulations prepared using ion exchange → IV or IM
• Standard dose is 300ug or 1500 IU – will protect an
average-sized mother from a fetal hemorrhage of up to
30ml of fetal whole blood or 15ml of fetal red cells
• Given at 28 weeks initially, 2nd dose given after delivery
if the newborn is D-positive
• Administration of immune globulin is recommended
ONLY AFTER THE NB IS CONFIRMED TO BE D POSITIVE
• All D negative women should be screened at delivery
with a rosette test
o Qualitative test that identifies whether fetal
D-positive cells are present in the circulation
of a D-negative woman
o If there are rosettes → there are fetal D
positive cells in that sample
• If Rhogam is given IM (max of 5 doses in 24 hrs.)
• If IV → 2 ampules (total of 600ug) may be given every 8
hours
FETOMATERNAL HEMORRHAGE
• Incidence increases with advancing gestation and the
volume of fetal blood in the maternal circulation
• Most common complaint is decrease fetal movement if
fetomaternal hemorrhage is suspected, an elevated
MCA peak systolic velocity or sonographic evidence of
hydrops prompts consideration of urgent fetal
transfusion or delivery
Laboratory Tests:
• Volume of fetal blood loss should be estimated to
calculate appropriate dose of anti D-immune globulin if
the woman is D-negative
44
 • Most common: Kelihauer-Betke test
o After exposure to acid only fetal Hgb remains
FETAL THROMBOCYTOPENIA
Alloimmune Thrombocytopenia
• Aka: Neonatal Alloimmune thrombocytopenia (NAIT) or
fetal and neonatal alloimmune thrombocytopenia
(FNAIT)
• Most common cause of severe thrombocytopenia
among term newborns
• Caused by maternal alloimmunization of paternally
inherited fetal platelet antigens
• Maternal platelet count is normal
• Most often against human platelet antigen-1a (HPA-1a)
• 80-90% of cases and associated with the greatest
severity
• Newborn may manifest petechiae
Diagnosis and Management:
• Diagnosis made following delivery of a neonate with
severe and unexplained thrombocytopenia to a woman
whose platelet count is normal
• CS at or near term
• If fetal blood sampling reached a platelet count of
>100,000, assisted vaginal delivery may be attempted
Immune Thrombocytopenia
• AKA Idiopathic thrombocytopenic purpura (ITP)
characterized by anti-platelet IgG antibodies that attack
platelet glycoproteins
• Usually, mild
• Neonatal platelet levels may fall rapidly after birth with
a nadir at 48-72 hours of life
HYDROPS FETALIS
• Excessive accumulation of serous fluid
• 2 or more fetal effusions – pleural, pericardial or ascites
• Usually accompanied by placentomegaly and
hydramnios
• Sonographically determined as skin thickness >5mm
and placentomegaly if the placenta thickness is at least
4cm in the 2nd trimester or 6cm in the 3rd trimester
• Immune or nonimmune
IMMUNE HYDROPS
• Declined with advent of anti-D Ig and MCA doppler
studies
• Pathophysiology remains unknown
• Decreased colloid oncotic pressure, increased
hydrostatic pressure and enhanced vascular
permeability
• Results from transplacental passage of maternal
antibodies that destroy fetal red cells
• Treated with fetal blood transfusion
NON-IMMUNE HYDROPS
• At least 90% of cases
• 20% are due to unknown cause / idiopathic
• Aneuploidy accounts for approximately 20%, CV
abnormalities for 15% and infections for 14% → most
common infection is parvovirus B19
• Only 40% result to a liveborn newborn
• Most frequent aneuploidy associated with hydrops →
45, X Turner syndrome (survival rate <5%)
• If detected in the 1st trimester → aneuploidy risk if 50%
and most have cystic hygroma
• Diagnostic Evaluation:
o Readily detected sonographically
o Indirect coombs test for alloimmunization
o Amniocentesis
o Kelihauer-Betke test for fetomaternal
hemorrhage if anemia is suspected
o Consideration of testing for alpha thal and/or
inborn errors of metabolism
MIRROR SYNDROME
• Association between fetal hydrops and development of
maternal edema in which the fetus “mirrors” the
mother
• A form of severe pre-eclampsia (same symptoms)
• Prompt delivery is indicated followed by resolution of
maternal edema and other findings
CHAPTER 16
Fetal Therapy
MEDICAL THERAPY
ARRHYTHMIAS
Premature Atrial • Most common arrhythmia (1-2% of
Contractions pregnancies_
• Immaturity of cardiac conduction system
→ resolve later in gestation
• Sounds like an extra beat when auscultated
with doppler
• 2% later have SVTs
Tachyarrhythmias • 2 most common: SVT, atrial flutter
• SVT: 180-300bpm
• Atrial flutter: 300-500bpm
• Important to determine if it is sustained
(present for at least 50% of the time)
• Risk for hydrops if sustained
45
 • Maternal administration of antiarrhythmic • CVR >1.6 → 60% chance of hydrops
agents that cross the placenta • Corticosteroid Tx has been used in an effort to improve
• Digoxin, sotalol, flecainide, * procainamide outcome
• SVT more likely than atrial flutter to • Dexa 6.25mg every 12 hrs. x 4 doses or beta 12.5mg
convert to a normal rhythm every 24 hrs. for 2 doses
Bradyarrhythmia • Most common etiology: congenital heart
block THYROID DISEASE
• Prognosis if 2ndary to a structural cardiac Fetal • Goiter, tachycardia, growth restriction,
anomaly is extremely poor (80% mort) thyrotoxicosis hydramnios, accelerated bone maturation,
• Many women have subsequent SLE or heart failure, hydrops
other CT disease • Cause: maternal Graves disease with
• Risk of third deg heart block is 2% transplacental passage of IgG thyroid
• Hydroxychloroquine (Plaquenil) – mainstay stimulating immunoglobulins
Tx for SLE • Fetal blood sampling will confirm the
*first line diagnosis
• Atrial bigeminy – benign and does not require • If mother develops hypothyroidism →
treatment levothyroxine
Fetal • Transplacental passage of methimazole or
CONGENITAL ADRENAL HYPERPLASIA hypothyroidism PTU may cause it (if mother is receiving
• Impaired fetal synthesis of cortisol from cholesterol by medication for Graves)
the adrenal cortex • May lead to hydramnios, neck
• Most common etiology of androgen excess in females hyperextension and delayed bone
with 46, XX, disorders of sex development formerly maturation
female pseudohermaphroditism • Discontinuation of antithyroid medications
• Lack of cortisol → ACTH secretion by anterior pituitary is generally recommended
→ androstenedione and testosterone overproduction
→ virilization of female fetus SURGICAL THERAPY
• More than 90% are caused by 21-hydroxylase deficiency • IF likelihood of fetal deterioration is so great that
• 75% at risk for salt wasting adrenal crisis and require delaying treatment until after delivery would risk fetal
postnatal treatment with mineralocorticoids and death or substantially greater postnatal morbidity
glucocorticoids to prevent hyponatremia, dehydration, GUIDING PRINCIPLES FOR FETAL SURGICAL PROCEDURES
hypotension and CV collapse • Accurate prenatal diagnosis
• 25% simple virilizing type – require glucocorticoids • Defect appears isolated with no evidence of other
• Preventive regimen: maternal oral dexa (20ug/kg/d up abnormality or underlying genetic syndrome that would
to 1.5mg/day) divided into 3 doses worsen survival or QOL
• Critical period for development of external genitalia is • Defect results in death or irreversible organ destruction
7-12 weeks and treatment to prevent virilization should • Procedure is feasible
be initiated by 9 weeks • Maternal risks well documented and considered
• Carrier parents are identified after birth of an affected acceptable
child • Comprehensive parental counselling
• Goal of prenatal diagnosis is to limit dexa exposure in • Animal mode for defect and procedure recommended
males and in unaffected females Open Fetal Surgery
• Prenatal molecular genetic testing performed on • Mother must undergo GA to suppress uterine
chorionic villi at 10-12 weeks or on amniocytes after 15 contractions and fetal responses
weeks • Warmed fluid continuously infused into the uterus
• Determination of fetal gender when performed at or through rapid infusion
beyond 7 weeks has 95% sensitivity • Tocolysis (mag sulfate for 24 hrs, oral indomethacin for
48 hrs, oral nifedipine until delivery)
CONGENITAL CYSTIC ADENOMATOID MALFORMATION (CCAM) • Prophylactic antibiotics given and continued for 24 hrs
• Well circumscribed lung mass that may appear solid and following the procedure
echogenic or may have one or multiple variably sized Risks:
cysts • Pulmonary edema
• >5mm → macrocystic • Placental abruption
• AKA: congenital pulmonary airway malformation • Blood transfusion
(CPAM) • PPROM
• Overgrowth of terminal bronchioles • Preterm delivery
• Mass may become so large → mediastinal shift → Myelomeningocele • First nonlethal birth defect for which fetal
compromised cardiac output and venous return → Surgery surgery has been offered
hydrops Thoracic Masses • Reserved for cases prior to 32 weeks in
• CCAM-volume ratio to quantify size and risk for hydrops which hydrops is developing
(CVR)
• Use of EXIT procedure
46
Sacrococcygeal • Germ cell tumor (1 in 28,000 births)
teratoma • Solid and/or a cystic mass that arises from
the anterior sacrum
• Hydramnios is common due to high
output cardiac failure
• Poor prognostic factors include a solid
component compromising more than 50%
of the tumor
• Fetal loss 100% if hydrops or
placentomegaly develop
• Only in tumors are completely external
(type 1)
Fetoscopic Surgery
Twin to Twin • Fetoscopic laser ablation of placental
Transfusion anastomoses is the preferred management for
Syndrome severe TTTS
• Performed 16-26 weeks AOG with sage 2-4
TTS
• Solomon Technique: after selective
photocoagulation, the laser is used to
coagulate the entire vascular equator from
one edge of the placenta to the other →
lowers proportion of pregnancies with
recurrent TTTS and TAPS
Congenital • Main cause of mortality in isolated CDH:
Diaphragmatic pulmonary hypoplasia and pulmonary
Hernia hypertension
• Major risk factor: liver herniation
• Lung to head ratio: measurement of right lung
area taken at the level of the 4-chamber view
divided by the head circumference → survival
rate 100% if the LHR >1.35
• MRI used to estimate total volume of lung
tissue
• Liver herniation is the strongest predictor of
outcome
• Liver volume more reliable predictor because
lungs are inherently more compressible
• Tracheal Occlusion / Fetal Endoscopic
Tracheal Occlusion (FETO): performed 27-30
weeks → balloon occlusion
Percutaneous Procedures
Thoracic • Most common etiology of primary effusion is
Shunts chylothorax (caused by lymphatic
obstruction)
• May also be due to congenital viral infection,
aneuploidy or a malformation such as
pulmonary sequestration
• Pleural fluid cell count >80% lymphocytes →
diagnostic of chylothorax
• If effusion is R sided → shunt is placed in the
lower third of the chest to permit maximum
expansion of the lung
• If effusion if L sided → shunt placed along
upper axillary line to allow the heart to
return to normal position
• Shunt placement may improve survival to
90% in the absence of hydrops and >75% if
with hydrops
Urinary Shunts • Distal obstruction of the urinary tract occurs
more often in male fetuses
• Most common etiology is posterior urethral
valves, urethral atresia and by prune belly
syndrome / Eagle Barrett syndrome
• UTZ shows dilation of the bladder and
proximal urethra “keyhole sign:
• Chromosomal Microarray Analysis
recommended
• Only offered when fetus is male
Radiofrequency • Favored modality for treatment of twin-
Ablation reversed arterial perfusion sequence (TRAP) /
acardiac twin
• Gauge 17 or 19 needle directed into the base
of the umbilical cord of the acardiac twin
Fetal • Aortic valvuloplasty for critical aortic stenosis
Intracardiac o Most commonly performed procedure
Catheter (75%)
Procedures o Goal: prevent progression to
hypoplastic left heart and permit
postnatal biventricular repair
• Atrial septostomy for hypoplastic left heart
syndrome
• Pulmonary valvuloplasty for pulmonary
atresia with intact interventricular septum
•
EX-UTERO INTRAPARTUM TREATMENT (EXIT)
• Allows fetus to remain perfused by the placenta after
being partially delivered so that lifesaving treatment
can be performed before completing delivery
• Preferred procedure for intrapartum management of
large venolymphatic malformations of the neck
• Other indications: severe micrognathia and congenital
high airway obstruction sequence (CHAOS)
• For micrognathia – fetal jaw measurement below the
5th percentile along with indirect evidence of
obstruction (hydramnios) and an absent stomach
bubble
• Associated with greater blood loss, higher incidence of
wound complications, longer operating time (40
minutes longer than CS)
CHAPTER 17
Fetal Assessment
FETAL MOVEMENTS
Physiology:
• Beyond 8 menstrual weeks fetal body movements are
never absent for periods exceeding 13 minutes
• 20-30 weeks: general body movements become
organized and the fetus shows rest-activity cycles
• Fetal movement maturation continues until
approximately 36 weeks
• 4 behavioral states:
State 1F • Quiescent stage – quiet sleep with a
narrow oscillatory bandwidth of the
fetal heart rate
47
 • Bladder volumes increased during 1F
quiet sleep
State 2F • Frequent gross body movements,
continuous eye movements, wider
oscillation of the FHR
• Analogous to rapid eye movement
(REM)
• FHR baseline bandwidth increased
appreciably, and bladder volume was
diminished due to decreased urine
production and infrequent fetal voiding
State 3F • Continuous eye movements in the
absence of body movements and no
heart rate accelerations
State 4F • Vigorous body movement with
continuous eye movements and HR
accelerations
• Corresponds to awake state in
newborns
*in purple – where fetuses spend most of their time in,
correspond to quiet and active sleep
• Fetal sleep cyclicity varies from 20-75 minutes (mean:
23 minutes)
• AFV is another important determinant of fetal activity
• As pregnancy advances → rate of weak movements
decreases, and movements become more vigorous for
several weeks and the subside at term
FETAL BREATHING
• Paradoxical chest wall movement
• 2 types of chest movements
o Gasps / Sighs: occurred at a frequency of 1-4
per minute
o Irregular bursts of breathing: occurred at
rates up to 240 cycles per minute
CONTRACTION STRESS TESTING
• A test of uteroplacental function
• As amnionic fluid pressure rises with uterine
contractions → myometrial pressure exceeds collapsing
pressure for vessels coursing through the uterine
muscle → lowers blood flow to intervillous space →
brief periods of impaired oxygen exchange → if
uteroplacental pathology is present → late
decelerations
• Requires 90 minutes to complete
• If at least 3 spontaneous contractions of 40 seconds or
longer are present in 10 minutes → no uterine
stimulation necessary
• If fewer → nipple stimulation
o 2 minute stimulation ideally will induce 3
contractions per 10 minutes
▪ If not after a 5 minute interval →
retry nipple stimulation → if
unsuccessful → oxy
• Start oxy at 0.5mU/min and doubled every 20 minutes
until a satisfactory contraction pattern is established
Criteria for Interpretation of the CST
Negative No late or significant variable decelerations
Positive Late decelerations following 50% or more of
contractions (even if contraction frequency is
fewer than 3 in 10 minutes)
Equivocal – Intermittent late decelerations or significant
suspicious variable decelerations
Equivocal – Decelerations that occur in the presence of
hyperstimulatory contractions more frequent than every 2
minutes or lasting >90 seconds
Unsatisfactory Fewer than 3 contractions in 10 minutes or
an uninterpretable tracing
NON-STRESS TEST
• A test of fetal condition
Fetal HR Acceleration
• Autonomic influences are mediated by sympathetic or
parasympathetic impulses from brainstem centers to
normally raise or slow the FHR
• Beat to beat variability is also under ANS
• Loss of reactivity is most commonly associated with
sleep cycles
• Percentage of body movements that is accompanied by
accelerations and amplitude of these accelerations both
increase with GA
• Beyond 32 weeks: 15bpm lasting 15 secs less than 2
mins
• Before 32 weeks: 10bpm for 10 seconds in 2 minutes
Normal NST
• 2 or more accelerations peaking at 15bpm lasting 15
seconds or more occurring within 20 minutes of
beginning the test
Abnormal NST
• If nonreactive for 90 minutes → 93% associated with
significant perinatal pathology
• Terminal cardiotocogram:
o Baseline oscillation of less than 5pm
o Absent accelerations
o Late decelerations with spontaneous uterine
contractions
Interval between Testing
• 7 days
• Post term, multifetal, pregestational diabetes, fetal
growth restriction or hypertension → 2x a week
Decelerations during NST
• Variable decelerations if not repetitive and brief (<30
seconds) do not indicate fetal compromise
• Repetitive variable decelerations (3 in 20 minutes) even
if mild have been associated with a greater risk of CS for
fetal distress
False Normal
• Single most common autopsy finding in infants who
died within 7 days from last NST → meconium
aspiration
ACOUSTIC STIMULATION TESTS
48
 • Stimulus of 1-2 seconds is applied and may be repeated Umbilical • Abnormal if it is >95th percentile for AOG or if
up to 3x for 3 seconds artery diastolic flow is absent or reversed
• Positive → rapid appearance of a qualifying velocimetry • Result from poorly vascularized placental villi
acceleration after stimulation • Seen in extreme cases of fetal growth
BIOPHYSICAL PROFILE restriction
• Components assessed: • ACOG: not shown to improve perinatal
o HR acceleration outcome
o Breathing MCA • Brain sparing
o Movements • Useful for detection and management of fetal
o Tone anemia of any case
o AFV Ductus • Best predictor of perinatal outcome
Compo SCORE 2 SCORE 0 venosus • Negative or reversed flow in the DV was a late
HR accel (NST) >2 accels of >15 bpm 0 or 1 accel within finding
for 15 secs within 20-40 20-40 mins
Uterine Artery • Vascular resistance in the uterine circulation
mins
Fetal breathing >1 ep of rhythmic <30 sec of breathing normally decreases in the first half of
breathing lasting >30 within 30 min pregnancy due to invasion of maternal uterine
sec within 30 mins vessels by trophoblastic tissue
Fetal movement >3 discrete body or limb < 3 discrete • Most helpful in assessing pregnancies at high
movements within 30 movements risk for uteroplacental insufficiency
mins
Fetal tone >1 ep of extremity 0 flexion / extension ACOG
extension and
subsequent return to
“A normal antepartum fetal test result is highly reassuring that a
flexion stillbirth will not occur within 1 week”
AFV Pocket of AF that Largest SVP <2cm
measures at least 2 cm
in 2 planes (2x2cm CHAPTER 18
pocket)
Modified BPS
• Includes NST
Abortion
• Spontaneous or induced termination of pregnancy
Interpretation of BPS
Score Interpretation Mx
before fetal viability
10 Normal nonasphyxiated No indication for • Pregnancy loss <20 weeks AOG with a fetus delivered
fetus intervention weighing <500g
8/10 (normal AFV) Normal nonasphyxiated No indication for • Yolk sac diameters ≥6mm in pregnancies <10 weeks are
fetus intervention suspicious for pregnancy failure
8/8 (NST not done) FIRST TRIMESTER SPONTANEOUS ABORTION
8/10 (decreased Chronic fetal asphyxia Deliver
• Demise of the embryo or fetus nearly always precedes
AFV) suspected; possible fetal
asphyxia spontaneous expulsion
6 Possible fetal asphyxia If AFV is abnormal: • Death of fetus → hemorrhage into decidua basalis →
delivery adjacent tissue necrosis → uterine contractions
If normal >36 wks. + Fetal factors:
favorable cx → • Half are euploid abortions (carrying a normal
delivery chromosomal complement), the other half has a
If repeat test >6 chromosomal abnormality
observe and repeat
• Trisomies 13, 16, 18, 21 and 22 are most common
4 Probably fetal asphyxia Repeat testing same
day, if <6 → deliver • Monosomy X (Turner Syndrome) – single most frequent
0 to 2 Almost certain fetal Deliver specific chromosomal abnormality
asphyxia • Triploidy – hydropic or molar placental degeneration
Maternal factors:
AFV • Infections
• Diminished uteroplacental perfusion → low fetal renal • Medical disorders: poorly controlled DM, obesity,
blood flow → decreased urine production → thyroid disease, SLE
oligohydramnios • Cancer: women exposed to methotrexate, those who
underwent RAI
DOPPLER VELOCIMETRY • Surgical procedures: if performed before 10 weeks
• Reflects downstream impedance AOG, supplemental progesterone should be given
• Nutrition: abortion is rare even in those with
hyperemesis gravidarum
Doppler BF • Abnormal waveforms correlated with
velocity placental hypovascularity • Social and behavioral factors: alcohol, smoking,
excessive caffeine consumption (5 cups of coffee per
• 60-70% must be obliterated before umbilical
day)
artery doppler waveform becomes abnormal

49
 • Occupational and environmental factors: environmental • PPROM at a previable gestational age complicates 0.5%
toxins suggested to have a possible link to miscarriage of pregnancies
include bisphenol A, phthalates, polychlorinated • Rupture may be spontaneous or may follow an invasive
biphenyls and dichlorodiphenyltrichloroethane procedure such as amniocentesis or fetal surgery
Paternal factors: • AF will fern on a microscope slide or will have a pH >7
• Increasing paternal age or oligohydramnios in UTZ
o Amnionic fluid proteins placental alpha
SPONTANEOUS ABORTION CLINICAL CLASSIFICATION macroglobulin-1 and insulin GF binding
Threatened abortion: protein-1
• Bleeding through a closed cervical os during the first 20 • 40-50% will deliver within the first week and 70-80%
weeks will deliver after 2-5 weeks
• Serum beta hCG should rise at least 53-66% every 48 • Without bleeding, cramping, fever → expectant
hours management is an option
• Progesterone levels >20ng/ml support the diagnosis of • Antibiotics are considered and given for 7 days to
a healthy pregnancy extend latency
• GS seen at 4.5 weeks and beta hCG generally measures Septic Abortion
1500-2000mIU/ml (could be as low as 390mIU/ml) • May cause parametritis, peritonitis and septicemia
• YS at 5.5 weeks with a mean GS diameter of 10mm • Most bacteria causing septic abortion are part of
Incomplete abortion: normal vaginal flora
• Before 10 weeks, the fetus and placenta are expelled • S pyogenes – toxic shock syndrome
together • Clostridium perfringens – may also cause toxic shock
• Tissue may remain entirely within the uterus or partially syndrome
extrude through the cervix • Prompt administration of broad spectrum antibiotics
• Medical therapy carries failure rates of 5-30% • If with retained products of conception → curettage
• Curettage 95-100% successful • Imaging that shows free air or air within the uterine
Complete abortion: wall → laparotomy
• Complete expulsion + closure of cervical os • If uterus is necrotic → hysterectomy
• Cannot be surely diagnosed unless: Anti-D Immunoglobulin
o True products of conception are seen grossly • With spontaneous miscarriage → 2%will become
o Sonography confidently documents first a IUP alloimmunized if not provided passive isoimmunization
and then later an empty cavity • Anti-Rho (D) immunoglobulin given as 300ug IM for all
o Serum beta hCG levels drop gestational ages (doses may also be graduated with
Missed abortion: 50ug given IM for pregnancies <12 weeks and 300ug for
• Dead products of conception that have been retained >13 weeks) → administered immediately after surgical
for days or weeks in the uterus with a closed cervical os evacuation
• TVS is a primary tool • For planned medical or expectant management →
• At 5-6 weeks: 1-2mm embryo adjacent to the yolk sac injection is given within 72 hrs of pregnancy failure
can be seen diagnosis
• Absence of an embryo in a sac with an MSD >/=25mm • Still give anti-D immunoglobulin for threatened
signifies a dead fetus abortion and a live fetus
• Fetal cardiac activity can be detected at 6-6.5weeks
with a CRL of 1-5mm and an MSD of 13-18mm RECURRENT MISCARRIAGE
• A threshold CRL ≥7mm with absent cardiac activity is • 3 or more consecutive pregnancy losses <20 weeks or
also used to diagnose nonviability with a fetal weight of <500g
• Risk for a subsequent miscarriage following 2 or 3 prior
GUIDELINES FOR EARLY PREGNANCY LOSS DIAGNOSIS pregnancy losses are similar
• ASRM: RPL as 2 or more failed pregnancies confirmed
by sonographic or histopathologic examination
• Primary RPL: multiple losses in a woman who has never
delivered a liveborn
• Secondary RPL: multiple pregnancy losses in a patient
with prior live birth
• Chances for a successful pregnancy are >50% even
after 5 losses
# of prev 2 3 4 5
miscarriages Predicted Percentage Success of Subsequent
at Age Pregnancies
20 92 90 88 85
25 89 86 82 79
30 84 80 76 71
Inevitable abortion 35 77 73 68 62

50
 40+ 69 64 58 52
Etiology:
• Parental chromosomal abnormalities
• APAS
• Structural uterine abnormalities
• First trimester losses in RPL have a significantly lower
incidence of genetic abnormalities than sporadic
miscarriages
• Genetic factors → early embryonic losses
• Autoimmune or uterine anatomical abnormalities → 2nd
trimester losses
• 40-50% have idiopathic RPL
Parental Chromosomal Abnormalities
• 2-4%
• Karyotyping of both parents is considered essential
• Reciprocal translocations are most common followed by
Robertsonian translocations
• If + → offer IVF → preimplantation genetic diagnosis
• In couples with RPL who are chromosomally normal →
PGD not recommended
Anatomical Factors
• 15% of women with 3+ consecutive miscarriages will be
found to have a congenital or acquired uterine anomaly
• Uterine synechia – Asherman Syndrome – usually
results from destruction of large areas of the
endometrium following curettage or hysteroscopic
procedures or uterine compression sutures
• Leiomyomas – esp if located near placental
implantation site
• In women undergoing IVF pregnancy outcomes are
adversely affected by SM/SS/IM myomas
• Congenital genital tract anomalies often original from
abnormal Mullerian duct formation
• Unicornuate, bicornuate and septate uteri are
associated with all 3 types of loss
Immunologic Factors
• MC common in women with SLE
• Antiphospholipid antibodies – a family of
autoantibodies that bind to phospholipid-binding
plasma proteins
Clinical and Laboratory Criteria for Diagnosis of APAS
Clinical Criteria Obstetric: one or more unexplained deaths
of a morphologically normal fetus at or
beyond 10 weeks OR
Severe preeclampsia or placental
insufficiency necessitating delivery before
34 weeks OR
3 or more unexplained consecutive
spontaneous abortion before 10 weeks
Vascular: one or more episodes of arterial,
venous or small vessel thrombosis in any
tissue or organ
Laboratory Criteria Presence of LAC or
Medium or high serum levels of IgG or IgM
anticardiolipin antibodies or
Anti-beta 2 glycoprotein IgG or IgM
antibody
Endocrine Factors:
• Progesterone deficiency caused by a luteal phase defect
• PCOS
MIDTRIMESTER ABORTION
Incidence and Etiology:
• Fetal anomalies: chromosomal/structural
• Uterine defects: congenital / leiomyomas / incompetent
cervix
• Placental causes: abruptio, defective spiral artery
transformation, chorioamnionitis
• Maternal disorders: autoimmune, infections, metabolic
Management:
• Cervical cerclage
Cervical Insufficiency
• Painless cervical dilatation in the 2nd trimester
• Can be followed by prolapse and ballooning of
membranes into the vagina and ultimately expulsion of
an immature fetus
• Often repeats in future pregnancies
• Previous cervical trauma
• DES exposure may play a role
Surgical Indications:
• For women with an unequivocal history of second
trimester painless delivery
• Reinforces a weak cervix by an encircling suture
• Look for funneling in UTZ – ballooning of the
membranes into a dilated internal os but with a closed
external os
• Cervical length screening now recommended for
women with prior preterm birth between 16-24 weeks
AOG and completed every 2 weeks
• If an initial or subsequent cx length is 25-29mm →
weekly interval is considered
• If <25mm → cerclage is offered
• If WITHOUT history of prior preterm birth →
progesterone instead of cerclage
• Not recommended in twin pregnancies
Pre-surgical Preparation:
• Contraindications: bleeding, contractions, ruptured
membranes → high chance of failure
• Surgery between 12-14 weeks allows early intervention
• Culture of vagina (to check for gonorrhea or chlamydia)
Vaginal Cerclage:
• McDonald
• Shirodkar (modification of McDonald)
• Excellent outcomes
• No evidence to suggest need for antibiotic prophylaxis
• Regional anesthesia preferred
• McDonald:
o Nylon 1 or 2 or polypropylene monofilament
or 5mm Mersilene tape
o Suture is placed as high as possible and into
the dense cervical stroma
o 2 cerclage sutures
51
 • Rescue cerclage (thinned dilated cervix)
o Replace prolapsed amnionic sac back into the
uterus through steep Trendelenburg or filling
bladder with 600ml of saline through IFC
• For uncomplicated pregnancies without labor, cerclage
is usually cut and removed at 37 weeks to avoid cervical
laceration if labor commences
• Remove it even with cesarean delivery to avoid foreign
body complications
Transabdominal Cerclage:
• Suture placed at uterine isthmus can be used and left
until completion of childbearing
• Reserved for selected instances of severe cervical
anatomical defects or prior transvaginal cervical failure
Complications:
• Membrane rupture
o If during suture placement or within the first
48 hrs → remove cerclage because of the
likelihood of serious fetal or maternal
infection
• Preterm labor
• Hemorrhage
• Infection
INDUCED ABORTION
• Medical or surgical termination of pregnancy before the
time of fetal viability
• Abortion ratio: number of abortions per 1000 live
births
• Abortion rate: number of abortions per 1000 women
aged 15-44 years old
Therapeutic Abortion
• Termination of pregnancy for medical indications
• Most frequent indication: to prevent birth of a fetus
with significant anatomical, metabolic or mental
deformity
Elective Abortion/Voluntary Abortion
• Interruption of pregnancy before viability at the request
of the woman but not for medical reasons
FIRST TRIMESTER ABORTION METHODS
SURGICAL ABORTION: PREOPERATIVE PREPARATION
• Through an appropriately dilated cervix
• For ripening: hygroscopic dilators / osmotic dilators
o Devices that draw water from surrounding
tissues and expand gradually to dilate the
endocervical canal
o Laminaria algae: harvested from the ocean
floor
▪ Come in different diameters
▪ Takes 12-24 hours
o Dilapan-S: acrylic based gel
▪ Expands to an ultimate diameter 3-
4x of its dry state in 4-6 hours
o Misoprostol: 400ug sublingually, buccally or
placed into the posterior vaginal fornix 3-4
hours prior to surgery
o Antiprogestin mifepristone 200mg given
orally 24-48 hrs before surgery
o Prophylactic doxycycline 100mg orally 1 hr
before and then 200mg orally after
Vacuum Aspiration
• Aspiration of contents
NOTE
Frankenhäuser Plexus:
Supplies cervix, vagina and uterus and lies within connective
tissue lateral to the uterosacral and cardinal ligaments
ABORTION COMPLICATIONS:
• Complication rates rise with gestational age
• Uterine perforation – when instrument passes without
resistance deep into the pelvis
• Hemorrhage: excess of 500ml
• Infection
• Incomplete abortion may require reevacuation
NOTE
First trimester surgical abortion offers higher efficacy rates than
medical abortion
MEDICAL ABORTION:
• Mifepristone, methotrexate and misoprostol
• Contraindicated in:
o Current IUD
o Severe anemia, coagulopathy or
anticoagulant use
o Longer term systemic corticosteroid therapy
o Chronic adrenal failure
o Inherited porphyria
o Severe liver, renal, pulmonary or
cardiovascular disease
o Uncontrolled hypertension
ASSESSMENT:
• Measurements <15mm and <30mm after curettage =
successful evacuation
SECOND TRIMESTER ABORTION METHODS
DILATATION AND EVACUATION
• Mechanical cervical dilation precedes evacuation of
fetal parts
• Hygroscopic dilators are consistently effective for
cervical preparation before D&E
• For pregnancies >16 weeks, fetus is extracted in parts
using Sopher forceps → after removal of fetus, a large
bore vacuum curette is used to remove the placenta
Abnormal Placentation:
52
 • Placenta previa and accreta can raise D&E risks
• For previa → be ready for blood transfusion
• For accreta – hysterectomy
MEDICAL ABORTION
• Faster if vaginal or sublingual
• Prophylactic antibiotics are not typically given
POST ABORTAL CONTRACEPTION
• Ovulation may resume as early as 8 days, but average
time is 3 weeks
CHAPTER 19
Ectopic Pregnancy
TUBAL PREGNANCY
• 95% are implanted in various segments of the fallopian
tube
o Ampulla: 70%
o Isthmus: 12%
o Fimbria: 11%
o Interstitial tubal pregnancy: 2%
• 5% - ovary, peritoneal cavity, cervix or prior CS scar
• Heterotopic pregnancies – multifetal pregnancy
containing one conceptus with normal uterine
implantation that coexists with one implanted
ectopically
• Regardless of location, D-negative women with an
ectopic pregnancy who are not sensitized to D-antigen
are given IgG and anti-D Ig
RISKS:
• Increased 5fold after 1 ectopic pregnancy
• Prior STD or other tubal infections which can distort
tubal anatomy
• One episode of salpingitis can be followed by a
subsequent ectopic pregnancy in 9%
• Salpingitis isthmica nodosa: condition in which
epithelium lined diverticula extend into a hypertrophied
muscularis layer
• Congenital fallopian tube anomalies: usually secondary
to DES exposure
• Smoking
EVOLUTION AND POTENTIAL OUTCOMES:
• Outcomes: tubal rupture, tubal abortion or pregnancy
failure with resolution
• Pregnancy may pass out the distal fallopian tube
• Tubal abortion depends on the initial implantation site
→ distal implantations favored
• Bleeding can persist as long as products remain in the
tube → blood trickles from fimbria to peritoneal cavity
→ pools in the cul-de-sac
• Blood pools in the tube if the fimbria is blocked →
hematosalpinx
• Chronic ectopic pregnancy: abnormal trophoblast dies
early → low beta hCG levels → late rupture → or they
form a complex pelvic mass prompting diagnostic
surgery
CLINICAL MANIFESTATIONS:
• Classic triad: delayed mens, pain and vaginal bleeding
• With tubal rupture: abdominal and pelvic pain
• Bimanual exam: (+) CMT, bulging posterior vaginal
fornix from blood in the cul-de-sac or a tender boggy
mass beside the uterus, uterus can be slightly enlarged
• Other: diaphragmatic irritation from hemoperitoneum
causes neck or shoulder pain especially on inspiration
• Labs:
o Trending decline in Hgb or Hct
o Varying degrees of leukocytosis (as high as
30,000)
• Passing out of a decidual cast: entire sloughed
endometrium that takes the form of the endometrial
cavity
MULTIMODALITY DIAGNOSIS:
Beta hCG • ELISA test
• Lower limits: 20-25 mIU/ml for urine and <5
mIU/ml for serum
• Discriminatory threshold at >1500 mIU/ml or
>2000 mIU/ml or >3510 mIU/ml → indicative
of a live uterine pregnancy whereas
gestational sac was seen
• If initial beta hCG is below the set
discriminatory value → preg location is often
not seen via UTZ
• Following spontaneous abortion: hCG declines
by 21-35% in 48 hours and 68-84% at 7 days
Serum >25ng/ml excludes ectopic pregnancy
progesterone <5ng/ml nonliving IUP or an ectopic pregnancy
10-25ng/ml – in most ectopic pregnancies
TVS Endometrial findings: GS usually visible at 4-5
weeks, YS 5-6 weeks and fetal pole with cardiac
activity 5 ½ to 6 weeks
- Ectopic: trilaminar endometrial pattern
- Pseudosac: fluid collection between
the endometrial layers → if present,
risk for EP is increased
- Decidual cast: anechoic area lying
within the endometrium but remote
from canal
Adnexal findings: 60% of ectopic pregnancies
are seen as an inhomogeneous mass adjacent to
the ovary
20% appear as a hyperechoic ring
13% have an obvious GS with a fetal pole
- Ring of fire: placental blood flow
within the periphery of the complex
adnexal mass (can also be seen in a
corpus luteum)
Culdocentesis - Blood in the peritoneal cavity or cul-de-sac
- About 50ml can be seen in the cul-de-sac
using TVS
- Free fluid in the Morison pouch (near the
liver) is seen if volumes reach 400-700ml
- Peritoneal fluid with an adnexal mass is highly
predictive of an ectopic pregnancy
- 18 gauge needle is inserted through the
posterior vaginal fornix into the rectouterine
cul-de-sac → if present = fluid can be
53
 aspirated • Tubal rupture
Endometrial - Decidual reaction found in 42%
sampling - Secretory endometrium in 22% MTX Precautions:
- Proliferative endometrium: 12% • May interfere with tetracyclines, salicylates,
- Inaccurate in nearly 40% of cases without sulfonamides
histological exclusion of a spontaneous • NSAIDs may impair renal clearance
pregnancy loss • Vitamins with folic acid lower its efficacy
- Frozen section of curettage fragments to
identify products of conception is accurate in What is Leucovorin?
more than 90% of cases • Folinic acid prevents bone marrow depression with
Laparoscopy - Direct visualization of the FT and pelvis can is early administration
a reliable diagnosis • Allows for some purine and pyrimidine synthesis to
buffer the side effects of MTX
MEDICAL MANAGEMENT
• Methotrexate – folic acid antagonist Patient Selection
o Tightly binds to dihydrofolate reductase → • Asymptomatic, motivated and compliant patient!
blocks the reduction of dihydrofolate to • Low initial serum beta hCG – single best predictor of
tetrahydrofolate → de novo purine and successful treatment with single dose MTX
pyrimidine synthesis is halted → arrested Beta hCG level (mIU/ml) Chance of failure from
DNA, RNA and protein synthesis MTX therapy
o Effective against rapidly proliferating tissue <1,000 1.5%
such as trophoblast 2,000-5,000 3.8%
o 90% effective with its use 1,000-2,000 5.6%
o Side effects: bone marrow, GI mucosa and 5,000-10,000 14.3%
respiratory epithelium
• Small ectopic pregnancy size (<3.5cm) ~ 87-90% success
o Directly toxic to hepatocytes
rate
o Renally excreted
• Absent fetal cardiac activity
o Potent teratogen
o Excreted into breastmilk
Treatment Side Effects:
Medical Treatment Protocols for Ectopic Pregnancy
Organ System Percentage of SE
Single Dose Multidose
Liver involvement 12%
Dosing One dose, repeat if Up to 4 doses of
Stomatitis 6%
necessary both drugs until
Gastroenteritis 1%
serum beta hCG
declines by 15% • It does not diminish ovarian reserve! Great!
Dosage • Patients will experience increasing pain beginning
Methotrexate 50mg/m2 BSA (day 1mg/kg, days several days after therapy “separation pain” (ectopic
1) 1,3,5,7 pregnancy separating from the tubal wall)
Leucovorin NA 0.1mg/kg days
Monitoring Therapy Efficacy
2,4,6,8
• Tubal rupture can occur even when the beta hCG
Serum Beta hCG Days 1 (baseline) 4 Days 1 (baseline), 3,
plateaus or declines
level and 7 5, 7
• Overall success rate of MTX is 89% (single dose) and
Indication for If serum beta hCG If serum beta hCG
92.7% (multi dose)
additional dose level does not level declines <15%
decline by 15% give additional
from day 4 to day 7 dose; repeat serum
beta hCG in 48 hrs
and compare with
previous value,
maximum 4 doses
Surveillance Once 15% decline is achieved, weekly
serum beta hCG levels until undetectable

Methotrexate Contraindications: (HIPS BAIT)

• Hepatic, renal or hematologic dysfunction
SURGICAL MANAGEMENT
• Intrauterine pregnancy
• Laparoscopy is the preferred surgical treatment for
• Peptic ulcer disease
ectopic pregnancy unless a woman is hemodynamically
• Sensitivity to MTX
unstable
• Breastfeeding
• Salpingostomy vs salpingectomy
• Active pulmonary disease
Salpingostomy Salpingectomy
• Immunodeficiency
• 10-15mm linear incision • Tubal resection for both

54
 made on the antimesenteric
border of the FT
• Electrocoagulation and
incision are left unsutured
(heals by secondary
intention)
ruptured and unruptured o Displaces the round ligament upward and
• To minimize rare recurrence outward
of pregnancy in the tubal o Can sometimes be carried to term but with
stump increased risk of abnormal placentation
OTHER ECTOPIC PREGNANCIES

Persistent Trophoblast Ectopic Pregnancy Management

• Rare following salpingectomy but complicates 5-15% of Cesarean Scar Pregnancy • Expectant management is an
salpingostomies • Implantation within the option
• Bleeding caused by retained trophoblast is the most myometrium of a prior • Risks: hemorrhage, placenta
serious complication cesarean delivery scar accreta and uterine rupture
• Incomplete removal of trophoblast can be identified by • Incidence is 1 in 2000 • Hysterectomy is an acceptable
stable or rising beta hCG levels normal pregnancies choice in those desiring
• Pain and bleeding are sterilization
MEDICAL VERSUS SURGICAL common • MTX may be given if fertility
• Medical and surgical intervention provided similar 2 • MR imaging is useful preserving
year rates of attaining a uterine pregnancy when sonography is • Visually guided suction
inconclusive curettage, hysteroscopic
EXPECTANT MANAGEMENT removal or isthmic excision done
• May observe in cases with stable or falling serum beta abdominally or vaginally
hCG • Uterine AVM are a potential long
• In ectopic pregnancies measuring <3cm with beta hCG term complication
<1500 mIU/ml → most resolved without intervention Cervical Pregnancy • Conservative management
• Rare strives to minimize hemorrhage,
INTERSTITIAL PREGNANCY • Cervical glands noted resolve pregnancy and preserve
• Implantation within the proximal tubal segment that histologically opposite fertility
lies within the muscular uterine wall the placental attachment • MTX has become the first line
• Specific risk factor: previous ipsilateral salpingectomy site and by all or part of therapy in stable women
• Usually rupture after 8-16 weeks of amenorrhea the placenta found • MTX can be directly injected into
(greater distensibility of the myometrium covering the below the entrance of the gestational sac
interstitial fallopian tube segment) the uterine vessels or • Chemoembolization (uterine
below the peritoneal embolization + MTX)
• Hemorrhage can be severe and associated with
mortality rates as high as 2.5%!
reflection on the anterior • Suction curettage or
uterus hysterectomy
• Endocervix is eroded by • Urinary tract injuries are
A MISNOMER!!!
trophoblast and common
Interstitial pregnancies are incorrectly called “cornual
pregnancy develops in
pregnancies” BUT cornual pregnancies are those that describe a
the fibrous cervical wall
conception that develops in the rudimentary horn of a uterus
• Predisposing risks: ART
with a Mullerian anomaly
and prior uterine
curettage
Criteria for diagnosis and may aid in differentiation:
• Painless vaginal bleeding
• Empty uterus
(1/3 have massive
• A GS seen separate from the endometrium and >1cm
hemorrhage)
away from the most lateral edge of the uterine cavity
• Identification is based on
• A thin (<5mm) myometrial mantle surrounding eh sac
speculum examination,
• Interstitial line sign – a line extending from the GS to
palpation and TVS
the endometrial cavity representing the interstitial
Abdominal Pregnancy: • Depends on the gestational age
portion of the fallopian tube
• Implantation in the and diagnosis
Management:
peritoneal cavity • Termination generally is
• Cornual resection or cornuostomy via laparotomy or
exclusive of tubal, indicated when the diagnosis is
laparoscopy depending on patient’s hemodynamic
ovarian or made
stability and surgeon expertise
intraligamentous
• Intramyometrial vasopressin injection may limit surgical
implantations
blood loss
• Wedge excision
Ovarian Pregnancy • Surgical
• Cornuostomy: incision of the cornua and suction or 4 clinical criteria: • Ovarian wedge resection or
instrument extraction of the pregnancy 1. Ipsilateral tube is intact cystectomy
• Angular pregnancy: implantation within the and distinct from the
endometrial cavity but at one cornu and medial to the ovary
uterotubal junction and round ligament
55
2. Ectopic pregnancy
occupies the ovary
3. Ectopic pregnancy is
connected by the
uteroovarian ligament to
the uterus
4. Ovarian tissue can be
demonstrated
histologically amid the
placental tissue
• Associated with ART or Epidemiology and Risk Factors:
IUD failure Strongest risk factors:
• Rupture at an early stage • Prior H. mole (risk for recurrence is 0.9% for complete
is a consequence H. mole, 0.3% for partial H. mole)
Other Ectopic Sites • Laparotomy or laparoscopy • Women at extremes of age (36-40 yrs. -2fold risk, older
• Mesosalpinx / than 40 -10fold risk)
intraligamentous or • After 2 prior complete moles → 20% of women have a
broad ligament third mole
pregnancy Pathogenesis:
• Omentum, liver, • Arise from chromosomally abnormal fertilization
retroperitoneum • Thyrotropin-like effects of hCG frequently cause serum
fT4 levels to be elevated and TSH to be decreased
CHAPTER 20 • Severe preeclampsia and eclampsia are relatively
common with advanced molar pregnancies

Gestational Trophoblastic Disease COMPLETE H. MOLE PARTIAL H. MOLE

• Group of tumors typified by abnormal trophoblast Karyotype 46, XX 69, XXX or 69, XXY
proliferation Clinical Presentation
• Trophoblast produce hCG Preliminary Molar gestation Missed abortion
• GTD histologically is divided into hydatidiform moles Diagnosis
(presence of villi) and nonmolar trophoblastic malignant Uterine size Large for date Small for date
neoplasms (no villi) Theca lutein 25-30% of cases Rare
Hydatidiform Moles Nonmolar Trophoblastic cysts
Malignant Neoplasms Initial hCG >100,000 mIU/ml <100,000 mIU/ml
With villi No villi levels
Excessively edematous Trophoblastic cells Medical Uncommon Rare
immature placentas complications
Complete vs partial H. moles Choriocarcinoma, placental site Rate of 15-20% of cases 1-5% of cases
Malignant invasive moles trophoblastic tumor and subsequent
(marked penetration into and epithelioid trophoblastic tumor GTN
destruction of the Pathology
myometrium and its ability to Embryo-fetus Absent Often present
metastasize) Amnion, fetal Absent Often present
erythrocytes
• Gestational trophoblastic neoplasia: malignant form of Villous edema Widespread Focal
GTD Trophoblastic Slight to severe Focal, slight to
o Invasive mole proliferation moderate
o Choriocarcinoma Trophoblast Marked Mild
o Placental site trophoblastic tumor atypia
o Epithelioid trophoblastic tumor P57 Negative Positive
immunostaining
o Develop weeks or years following any type of Sonography Echogenic mass with Thickened multicystic
pregnancy numerous anechoic placenta along with a
cystic spaces without fetus or at least fetal
a fetus or amnionic tissue
sac “snowstorm”
Median time 9 weeks 7 weeks
HYDATIDIFORM MOLE for resolution
• Trophoblast proliferation and villi with stromal edema
• Complete or partial moles
• GTN more frequently follows complete H. mole

56
 • Once beta hCG is undetectable → you still monitor
monthly for 6 months
• Contraception is important so as not to confuse beta
hCG levels with pregnancy
• IUD not recommended until beta hCG levels are
undetectable because of the risk of uterine perforation
• After 6 months → pregnancy is then allowed

GESTATIONAL TROPHOBLASTIC NEOPLASIA

Clinical Findings:
• Aggressive invasion into the myometrium and
propensity for metastasize
• Irregular bleeding associated with uterine subinvolution
COMPLETE H. MOLE • Myometrial perforation from trophoblastic growth →
• 46, XX formed if a 23,X-bearing haploid sperm intraperitoneal hemorrhage
penetrates a 23,X containing haploid egg whose genes Diagnosis, Staging and Prognostic Scoring
have been “inactivated” • Unusually persistent bleeding after any type of
• Paternal chromosomes duplicate → 46,XX diploid pregnancy should prompt measurement of serum beta
complement hCG
• Solely of paternal origin • Once diagnosis is verified → liver and renal function,
TVS, chest CT scan or CXR, brain and abdominopelvic CT
scan or MRI
• Staged clinically using FIGO
• WHO prognostic index score with which scores of 0-4
are given for each of the categories
• WHO scores of 0-6: low risk disease>7 is considered in
the high risk group

Criteria for Diagnosis of GTN

1. Plateau of serum beta hCG level for four measurements
during a period of 3 weeks or longer – days 1, 7, 14, 21
2. Rise of serum beta hCG level >10% during 3 weekly
PARTIAL H. MOLE consecutive measurements or longer during a period of
• 2 sperm (either 23,X or 23,Y) both fertilize (dispermy) a 2 weeks or more – days 1, 7, 14
23,X containing haploid egg whose genes have not 3. Serum beta hCG level remains detectable for 6 months
been inactivated → fertilized egg that is triploid with 2 or more
chromosome sets being donated by the father, termed 4. Histological criteria for choriocarcinoma
“diandry”
FIGO STAGING FOR GTN
Stage I Disease confined to the uterus
MANAGEMENT Stage II GTN extends outside of the uterus but limited to
• Chest radiography genital structures
• CT and MR reserved if with lung lesions on the CXR Stage III Extends to lungs with or without genital tract
Termination: involvement
• Molar evacuation by suction curettage is preferred Stage IV All other metastatic sites
treatment
• Oxytocin is infused to limit bleeding
• Sonography often recommended to help ensure
complete uterine cavity emptying
• Give RhoGAM post op
• Hysterectomy for women who have completed their
family size
• Theca lutein cysts seen at the time of hysterectomy do
not require removal since they regress
Post-evacuation Surveillance
• Serial measurement of beta hCG to detect persistent or
renewed trophoblastic proliferation
• Obtain initial beta hCG level within 48 hours after
evacuation (serves as baseline) then every 1-2 weeks
until levels are undetectable

57
 MODIFIED WHO PROGNOSTIC SCORING SYSTEM
Scores 0 1 2 4 TREATMENT
Age <40 >40 - - • Prognosis is excelling with rare exceptions and patients
are routinely cured even in the presence of widespread
Antecedent Mole Abortion Term - disease
pregnancy • Chemo alone is primary treatment
Interval after <4 4-5 7-12 >12 • Single agent chemo is usually sufficient for
index nonmetastatic or low risk metastatic neoplasia
pregnancy • Combination chemo is given for high risk disease
(mos.) • EMACO (etoposide, methotrexate, actinomycin D,
Pretreatment <10000 10,000- 100,000 – >1,000, cyclophosphamide and oncovin)
serum beta 100,000 1,000,000 000 • Adjuvant surgical and radiotherapy may also be
hCG employed
(mIU/ml) • Cause of death: hemorrhage from metastatic sites,
Largest <3cm 3-4cm >5cm - respiratory failure, sepsis, multiorgan failure
tumor size • Beta hCG Surveillance is continued for 1 year
(including • Effective contraception is crucial
uterus) • Quiescent hCG: despite no evidence of metastases have
Site of mets Spleen, GI Liver, very low beta hCG that plateau presumably caused by
kidney brain dormant trophoblast → close observation
Number of 1-4 5-8 >8
mets SUBSEQUENT PREGNANCY
Previous 1 >2
• No impaired fertility
failed chemo
• Pregnancy outcomes are usually normal
drugs
• 2% risk for developing trophoblastic disease in a
subsequent pregnancy
Histologic Classification
• Women who have successfully completed GTN
Invasive mole • Previously known as chorioadenoma destruens
chemotherapy are advised to delay pregnancy for 12
• Extensive tissue invasion by trophoblast and whole
villi months
• Penetration deep into the myometrium with • Send placenta for pathological evaluation after delivery
sometimes involvement of the peritoneum, of a normal fetus
adjacent parametrium or vaginal vault • Serum beta hCG is measured 6 weeks postpartum
• Less prone to metastasize
Gestational • Most common type of trophoblastic neoplasm to
Choriocarcinoma follow a term pregnancy or miscarriage CHAPTER 21
• Composed of cells reminiscent of early
cytotrophoblast and syncytiotrophoblast but
contains no villi Physiology of Labor
• Rapidly growing
• Invades both myometrium and blood vessels → • During the 36-38 weeks of normal gestation the
hemorrhage and necrosis myometrium is in a preparatory yet unresponsive state
• May spread outward on the uterine surface as dark
• Cervix begins an early stage of remodeling yet
irregular nodules
• Metastases often develop early and are blood
maintains structural integrity
borne • Prolonged uterine quiescence → myometrial
• Most common sites of mets: lungs, vagina, vulva, unresponsiveness is suspended → cervix undergoes
kidneys, liver, brain, ovaries, bowel ripening, effacement and loss of structural cohesion
• Common: theca lutein cysts
Placental site • Arises from intermediate trophoblasts at the MATERNAL AND FETAL COMPARTMENTS
trophoblastic placental site UTERUS:
tumor • Associated serum beta hCG levels that may only be
• Smooth muscle qualities of the uterus advantages:
modestly elevated
• Tx: hysterectomy (resistant to chemo) o Degree of SM cell shortening with
Epithelioid • Develops from chorionic type intermediate contractions is greater than that attained in
Trophoblastic trophoblast striated muscle cells
Tumor • Uterus – main site of involvement o Forces can be exerted in SM cells in multiple
• Bleeding and low hCG are typical findings directions
• Tx: hysterectomy (resistant to chemo) o SM is not organized (thick and thin filaments
• Mets is common are in long, random bundles→ aids in greater
shortening and force generating capacity)

58
 o Greater multidirectional force generation in
the fundus compared to the LUS permits
versatility in expulsive directional force

• Endometrium is transformed by pregnancy to decidua

o Serves to maintain pregnancy via unique
Target of
immunoregulatory functions that suppress NSAIDs
inflammatory signals during gestation
o Decidual activation at the end of pregnancy AKA COX1 and COX2

→ decidua transitions to induce inflammatory

signals and withdraw active Active
immunosuppression → initiation of prostaglandins
Upregulated during (PGE2 and PGF2a,
parturition pregnancy to rapidly PGI2
CERVIX inactivate
prostaglandins
Functions:
• Maintenance of barrier function to protect the
reproductive tract from infection THE PHASES OF PARTURITION
• Maintenance of cervical competence despite greater
gravitational forces as the fetus grows
• Orchestration of extracellular matrix changes that allow
progressively greater tissue compliance

PLACENTA
• Key source of steroid hormones, growth factors and
other mediators that maintain pregnancy
• Amnion provides all of the fetal membranes’ tensile
strength to resist membrane tearing and rupture
o Highly resistant to penetration by leukocytes, This corresponds to the major physiological transitions of the
microorganisms and neoplastic cells myometrium and cervix during pregnancy: 1) a prelude 2)
o Prevents AF contact with maternal tissues preparation 3) process itself 4) recovery
that could promote adverse events such as AF
embolism
• Chorion: primarily protective tissue layer and provides
immunological acceptance
o Enriched with enzymes that inactive
utertonins
▪ Prostaglandin dehydrogenase
▪ Oxytocinase
▪ Enkephalinase

SEX STEROID HORMONE ROLE

• Estrogen promotes
• Progesterone inhibits
o Withdrawal: precedes progression of
parturition

PROSTAGLANDINS ROLE
• Lipid hormones with varied hormone like actions
• Play a role in contractility, relaxation and inflammation
• Pathway:

59
 PHASE 1: UTERINE QUIESCENCE AND Myometrial Relaxation and Contraction
CERVICAL SOFTENING
What happens Key Roles Actin Myosin Regulation of Myometrial Gap G Protein Coupled Receptors Decidua and Cervical
Membrane Potentials Junctions and ER Softening
Stress Response
95% of pregnancy • Action of estrogen Quiescence is • Actin must be • Opening of the BKCa • Connexin-43 • Beta adrenoreceptors are • Synthesis in the decidua
Uterine SM and progesterone achieved in part converted from channels allow K to expressed in the prototypical examples of of prostaglandins is
tranquility with via intracellular by: globular to leave the cell to myometrium and CAMP → myometrial markedly suppressed
maintenance of receptors 1. Diminished filamentous form maintain interior concentrations rise relaxation • Suppression withdrawal
cervical structure • Myometrial cell intracellular • Actin must electronegativity near labor onset o Mediate G-stimulated is a perquisite for
integrity plasma membrane crosstalk and partner with and preventing • Important for increases in adenylyl parturition
Continues until receptor mediated reduced myosin → calcium influx and electrical cyclase, elevated • Decidual stromal cells
end of pregnancy increases in cAMP intracellular activates ATPase thus contraction myometrial levels of cAMP and ensure that fetal
Braxton Hicks • Generation of cyclic calcium levels → hydrolyzes ATP • Enhancing BKCa synchrony myometrial cell antigens do not elicit a
contractions guanosine 2. Ion channel → generates channel opening = • Contraction relaxation (agents maternal immune
monophosphate regulation of force (catalyzed myometrial associated proteins binding to these have response
Myometrial cells: (cGMP) cell membrane by the enzyme relaxation (CAPs) include been used for
Phenotypic • Modification of potential myosin light chain oxytocin receptor, tocolysis) Cervical Softening:
modification to a myometrial cell ion 3. Activation of kinase which is prostaglandin F • hCG activates adenylyl • Greater tissue
noncontractile channels uterine activated by Accelerated Utertonin receptor and cyclase → less contraction compliance
state → endoplasmic calcium → Degradation: connexin-43 frequency • Results from increased
unresponsive to reticulum calcium binds to • Activity of enzymes ER Stress Response • Prostaglandin E2 vascularity, cellular
natural stimuli 4. Uterotonin calmodulin to that inactivate • Progesterone mediates its diverse hypertrophy and
degradation activate myosin utertonins are maintains uterine cellular effects through 4 hyperplasia and slow,
light chain kinase) increased quiescence through G-protein coupled progressive
Contractility • Uterine relaxation • PGDH and myometrial caspase receptors compositional and
results from: is promoted by prostaglandin 3 (anticontractile • Relaxin binds to G-protein structural changes in
1. Enhanced lower Enkephalinase and agent) → degrades coupled receptor named the extracellular matrix
interactions concentrations of both actin and relaxin family peptide
endothelins , • Collagen – main
between actin calcium Oxytocinase and specific gap junction receptor 1 (RXFP1) → structural protein in the
and myosin oxytocin; deaminase protein, Connexin43 activates adenylyl cyclase cervix
2. Heightened • Prolonged ERSR → prevents intracellular
oxidase and • Contribute to tissue
excitability of histamine promotes caspase 3 Calcium → promotes compliance: lysyl
individual activation to quiescence hydroxylase and lysyl
myometrial cells preserve • Human Relaxin H1 and H2 oxidase
3. Promotion of quiescence o H1: decidua,
intracellular trophoblast and
crosstalk that prostate
allows o H2: corpus luteum
synchronous
contractions

60
PHASE 2: PREPARATION Progesterone Myometrial Changes Cervical Ripening Fetal Contributions to Parturition
FOR LABOR “UTERINE Withdrawal
AWAKENING” OR
ACTIVATION
• Progression of uterine • Changes in the • Prepare for labor • Involve connective tissue changes – cervical Uterine Stretch:
changes during the relative expression of contractions ripening • Required for induction of specific CAPs
last few weeks of the nuclear • Shift in the expression • Begins weeks or days before labor • Stretch → increases connexin-43 and oxytocin
pregnancy progesterone- of key proteins that • Cervical matrix changes its total amounts of receptors
receptor isoforms control quiescence → glycosaminoglycans and proteoglycans • Mechanotransduction: activation of cell surface
• Differential contraction- receptors or ion channels → transmission of signals
interaction of PR-A associated proteins Cervical Connective Tissue through ECM or release of autocrine molecules that
and PB-B with • Increase in CAPs • Collagen – extracellular matrix rich tissue act directly on the myometrium
enhancers and (myometrial oxytocin • Type I, III and IV collagens
inhibitors of gene receptors, gap • Collagen is responsible for the structural disposition Fetal Endocrine Cascades:
expression junction proteins and of the cervix • Critical component of normal parturition: fetal
• Alterations in PR connexin-43) hypothalamic-pituitary-adrenal-placental axis
activity through • Formation of the LUS Glycosaminoglycans and Proteoglycans o Premature activation of this → PTL
changes in the from the isthmus • Hyaluronan – high molecular weight polysaccharide • CRH levels are low in the 1st trimester → rise
expression of • Abdomen undergoes a that functions alone continuously from midgestation to term (peaks at
coactivators or shape change o Increases viscoelasticity, hydration and matrix delivery)
corepressors that Oxytocin Receptors: disorganization o During most of pregnancy → CRH binding
directly influence • Progesterone and o Synthesis is carried out by hyaluronan synthase protein (CRH-BP) binds most maternal
receptor function estradiol – primary isoenzymes (elevated during ripening) circulating CRH and inactivates it
• Local inactivation of regulators of oxytocin • Glycosaminoglycans (GAGs) complex with proteins o Placenta is source of elevated CRH
progesterone by receptor expression → proteoglycans o Enhances fetal cortisol production → positive
steroid metabolizing • 3 small leucine rich proteoglycans expressed in the feedback → placenta produces more CRH
enzymes or synthesis cervix: decorin, biglycan, fibromodulin Fetal Lung Surfactant and Platelet Activating Factor:
of a natural antagonist o Decorin interacts with collagen → regulate • Surfactant protein A (SP-A) produced by fetal lung is
• MicroRNA regulation packing, order and strength of collagen fibrils required for lung maturation
of progesterone Inflammatory Changes o Expressed in the human amnion and decidua
metabolizing enzymes • After delivery: proinflammatory gene expression and present in AF → prompts signaling
and transcription increased pathways in human myometrial cells
factors that modulate Induction of Cervical Ripening o SP-A selectively inhibits prostaglandin F2a in the
uterine quiescence • Direct application of prostaglandins PGE2 and PFG2a term decidua
→ modify extracellular matrix to aid ripening Fetal Membrane Senescence
Endocervical Epithelia • Cellular senescence “physiological aging”
• Lined with mucus secreting columnar and stratified • Stretch and oxidative stress → prompts senescent
squamous epithelia → mucosal barrier AND A fetal membrane to manifest a form of sterile
TIGHT JUNCTIONAL BARRIER TO PROTECT AGAINST inflammation “senescent-associated secretory
MICROBIAL INVASION phenotype” → propagates inflammatory signals to
decidua and myometrium to initiate parturition

Fetal Anomalies and Delayed Parturition

• Pregnancies with markedly diminished estrogen →
prolonged gestation
• Fetal adrenal glands important for timely onset of
parturition

61
 PHASE 3: LABOR FIRST STAGE SECOND STAGE THIRD STAGE
“ACTIVE LABOR”
• When spaced • Stage of cervical effacement and dilatation • When cervical dilatation is • Begins after delivery of the fetus and ends with delivery of the placenta
uterine Uterine Labor Contractions: complete and ends with • Stage of placental separation and expulsion
contractions • Bloody show indicates that labor is already in delivery • Uterine cavity is obliterated almost immediately after fetus is born (lies at
of sufficient progress or likely will ensue in hours to days Station: descent of the fetal the level of the umbilicus) → decrease in the area of placental
frequency, • Hypoxia of the contracted myometrium biparietal diameter in relation to a implantation → placenta thickens but because of limited placental
intensity and • Compression of nerve ganglia in the cervix and line drawn between maternal ischial elasticity it detaches
duration are lower uterus by contracted interlocking muscle spines • Decidua spongiosa – weakest layer that first separates
attained to bundles • Decline in uterine cavity surface area → amniochorion and parietal
bring about • Cervical stretching during dilatation Pelvic floor changes: decidual turn into pes innumerable folds →
cervical • Stretching of the peritoneum overlying the fundus • Most important component of • Schultze / Duncan
change • Ferguson reflex: mechanical stretching of the the floor: LEVATOR ANI and Uterotonins in Phase 3
termed cervix that enhances uterine activity FIBROMUSCULAR CONNECTIVE • Oxytocin: during phase 2, number of myometrial oxytocin receptor grows
“effacement” • Stripping: releases prostaglandin F2a metabolites TISSUE that covers its upper and o Synthesized in: magnocellular neurons of the supraoptic and
• Ends when Distinct Lower and Upper Uterine Segments lower surfaces paraventricular neurons → neurophysin → posterior pit gland
the cervix is • During contractions, muscles do not return to their • Levator ani: closes the lower end o Number of oxytocin receptors rises
fully dilated previous length, but tension remains the same of the pelvic cavity as a o Oxytocin acts on decidual tissue → PG release
to allow Changes in Uterine Shape diaphragm o Synthesized directly in decidual and extraembryonic fetal tissues
passage of • uterus elongates → greater fetal axis pressure o Varies in thickness from 3- • Prostaglandins
the fetus Ancillary Forces 5mm o Receptors for PGE2 and PGF2a are expressed in the uterus and cervix
• after cervix is fully dilated the most important o Undergoes hypertrophy → → will respond to prostaglandins
force in fetal expulsion is maternal forms a thick band that • Endothelin-1: 21-AA peptides that induce contraction; expressed in
intraabdominal pressure extends backward from pubis smooth muscle → causes a rise in intracellular calcium
Cervical Changes and encircles the vagina • Angiotensin II: AT1 and AT2 (G proteins)
• Cervical effacement – obliteration or taking up of about 2cm above the plane of o Nonpregnant: AT2 predominates
the hymen o Pregnant: AT1 predominates
the cervix
o Shortening of the cervical canal from approx. o Draws rectum and vagina o Binds to plasma membrane receptor → contraction
forward and upward in the
3cm to a mere circular orifice
o Lower segment and cervix have less resistance direction of the symphysis
pubis and acts to close the
during a contraction → centrifugal pull is
exerted on the cervix → cervical dilatation vagina
o Active phase: acceleration, phase of maximum
slope and deceleration phase
o Latent phase: more variable and sensitive to
extraneous factors (sedation may prolong
latent phase)
• Phase 4: The Puerperium: prompt remodeling processes that restore organs to the nonpregnant state ; Ovulation generally occurs within 4-6 weeks after birth

62
 Diagnosis
CHAPTER 22 • Leopold Maneuvers:
Maneuver Technique What is assesses
Normal Labor 1 Palpate the fundus Uterine fundus –
MECHANISM OF LABOR with palms cephalic or podalic
2 Palms placed on Where the fetal back
Pelvic Floor Changes
either side of the is
• Vaginal delivery is a traumatic event
maternal abdomen
• Levator hiatus area significantly larger at 37 weeks AOG
and gentle but deep
and 6 weeks postpartum compared with earlier pregnancy
pressure is exerted
Fetal Lie
3 Thumb and fingers of Aids in confirmation
• Relationship of the fetal long axis to that of the mother
one hand grasp the of fetal presentation
• 99% of the time – longitudinal
lower portion of the If presenting part is
• Transverse lie is less frequent maternal abdomen engaged a movable
o Risk factors: multiparity, placenta previa, just above the mass will be felt
hydramnios and uterine anomalies symphysis pubis
• Oblique lie: Fetal and maternal axis may cross at a 45- 4 Examiner faces Determines the
degree angle mother’s feet and degree of descent
Fetal Presentation fingertips of both
• Presenting part of the fetal body that is foremost within hands are positioned
the birth canal on either side of the
• Either fetal head or breech presenting part then
• Cephalic Presentation: you exert inward
o Vertex or occiput pressure and slide
o Sinciput presentation: when the neck is only caudad along the
partly flexed, the anterior fontanel may present axis of the pelvic
o Brow presentation: when neck is only partially inlet
extended, brow emerges
o As labor progresses, sinciput and brow almost Occiput Anterior Position:
always convert into vertex or face presentation • In most cases – vertex enters the pelvis with the sagittal
o Usually, fetus presents with vertex because the suture lying in the transverse pelvic diameter
uterus is piriform, or pear shaped • More commonly – fetus enters the pelvis in the left
• Breech Presentation: occiput transverse position
o Incidence drops with gestational age
o Frank, complete and footling
Fetal attitude:
• Characteristic posture
• “attitude” or “habitus”
• Fetus becomes folded upon itself to create a convex back,
head is sharply flexed, chin is almost in contact with the
chest, thighs are flexed over the abdomen, legs are bent at
the knees
Fetal Position:
• Relationship of an arbitrarily chosen portion of the fetal
presenting part to the right or left side of the birth canal
• Fetal occiput, chin and sacrum are the determining points
in vertex, face and breech presentations
• 2/3 of all vertex presentations are in the left occiput
position
• All transverse lies are shoulder presentations with either
back up or back down

63
Cardinal Movements of Labor
Main Points Fetal Head Shape Changes
Engagement • Biparietal diameter (the greatest transverse • Caput succedaneum: swelling in the portion of the fetal
diameter) passes through the pelvic inlet scalp, only a few ml
• Fetal head may engage during the last few weeks • Molding: changes in the bony fetal head shape as a result
of pregnancy of external compressive forces
• Fetal head usually enters pelvic inlet either o Possibly results from Braxton Hicks
transversely or obliquely o A “locking” mechanism at the coronal and
• Anterior asynclitism: sagittal suture approaches the lambdoidal sutures prevents overlapping
sacral promontory, more of the anterior parietal o Results in a shortened suboocipitobregmatic
bone is presenting diameter and a lengthened mentovertical
Posterior asynclitism: sagittal suture lies close to diameter
symphysis, more of the posterior parietal bone will o Most cases resolve within a week following
present delivery
Descent • First requisite for birth
• Multiparas – descent usually begins with NORMAL LABOR CHARACTERISTICS
engagement • Uterine contractions that bring about demonstrable
• Brought about by 1 or more of 4 forces: effacement and dilatation of the cervix
1. Pressure of AF
2. Direct pressure of the fundus FIRST STAGE OF LABOR
3. Bearing down efforts of mother
4. Extension and straightening of the fetal body Preparatory Cervix dilates little, Point at which the
Flexion • Descending head meets resistance whether from Division (Latent connective tissue mother perceives
the cervix, pelvic walls or pelvic floor → flexion phase) changes regular contractions
• Chin is brought into more intimate contact with the Affected by sedation Ends once dilation of
fetal thorax and the appreciably shorter and conduction 3-5cm is achieved
suboocipitobregmatic diameter is substituted for analgesia Prolonged latent
the longer occipitofrontal diameter phase: >20 hrs in
Internal • Movement turns the occiput gradually away from nullipara, >14 hrs in
Rotation the transverse axis multipara
• Essential for completion of labor except when the Dilatational Dilation proceeds at Mean duration in
fetus is small division its most rapid rate nulliparas: 4.9 hours
• 2/3 – internal rotation is completed by the time (Active phase) Dilation of 3-6cm or
the head reaches the pelvic floor • Acceleration more in the presence Maternal fear
Extension • Sharply flexed head reaches the vulva and • Phase of of uterine prolonged labor by
undergoes extension maximum slope contractions → approximately 45
• First force exerted by the uterus acts more • Deceleration threshold for active minutes
posteriorly and the second supplied by the labor
resistant pelvic floor rand the symphysis acts more Epidural anesthesia
anteriorly lengthens the active
phase by 1 hr
External • Delivered head undergoes restitution
Pelvic division Deceleration phase of Cardinal movements
rotation • Restitution of the head to the oblique position is
cervical dilatation take place
followed by external rotation completion to again
reach a transverse position
SECOND STAGE OF LABOR
• Serves to bring its bisacromial diameter into
relation with the anteroposterior diameter of the •Stage begins with complete cervical dilatation and ends
pelvic outlet with fetal delivery
Expulsion • Anterior shoulder appears under symphysis pubis • Mean duration: 50 minutes for nulliparas, 20 minutes for
multiparas
• Perineum becomes distended by the posterior
SUMMARY OF NORMAL LABOR:
shoulder → rest of the body follows
• Active labor can be reliably diagnosed when cervical
dilatation >3cm in the presence of uterine contractions
Occiput Posterior Presentation
• Normal labor may take more than 6 hrs to progress from
• 20% of the time
4-5cm and more than 3 hrs to progress from 5-6cm
• ROP is more common than LOP
• Labor accelerated much faster in multiparas
• More often associated with a narrow forepelvis
• Descent: Begins at 7-8cm in nulliparas and becomes rapid
• Anterior placentation
after 8cm
• Effective contractions, adequate head flexion and average
fetal size permit post posteriorly positioned occiputs to
rotate promptly as soon as they reach the pelvic floor
• If rotation is incomplete → transverse arrest
• If no rotation → persistent occiput posterior

64
MANAGEMENT OF NORMAL LABOR
Identification of Labor CHAPTER 23
• In the absence of ruptured membranes or bleeding,
uterine contractions 5 minutes apart for 1 hour may signify
labor onset Abnormal Labor
COMMON FINDINGS IN WOMEN WITH INEFFECTIVE LABOR
Initial Evaluation Inadequate cervical Protracted labor – slow progress
• Ruptured Membranes: dilation or fetal descent Arrested labor – no progress
o pH of vaginal secretions ranges from 4.5-5.5 Inadequate expulsive effort –
whereas that of AF is >7.0 ineffective pushing
o Nitrazine to identify ruptured membranes is a Fetopelvic disproportion Excessive fetal size
simple and fairly reliable method Inadequate pelvic capacity
o pH above 6.5 is consistent with ruptured Malpresentation or position of the fetus
membranes Abnormal fetal anatomy
o False positive results: blood, semen, BV Ruptured membranes
o Fern test: AF crystallizes to form a fernlike without labor
pattern due to its relative concentrations of
sodium chloride, proteins and carbohydrates ABNORMALITIES OF THE EXPULSIVE FORCES
• Cervical Assessment:
Types of Uterine Dysfunction
o Cervical effacement: reflects length of the
• Fundal dominance: forces are greatest and last longest at
cervical canal compared with the uneffaced
the fundus
cervix
o Position of the cervix • Lower limit of contraction pressure required to dilate the
o Fetal station: level of the presenting fetal part in cervix: 15mmHg
the birth canal in relationship to the ischial • Hypertonic uterine function: no basal hypertonus and
spines uterine contractions have a normal gradient pattern but
o ACOG: divides station into fifths pressure during a contraction is insufficient to dilate the
cervix
• Laboratory Studies
o Hemoglobin and hematocrit are assessed • Hypotonic uterine dysfunction or incoordinate uterine
dysfunction: either basal tone is elevated appreciably, or
Intrapartum Fetal Monitoring the pressure gradient is distorted (like more contractions
on the midsegment – asynchrony)
Technique First Stage Second Stage
Handheld doppler Immediately after a Every 15 minutes
LABOR DISORDERS
contraction and at
least every 30 Active Phase Disorders:
minutes • Protraction disorder – slower than normal
Hooked to monitor 30 minutes during At least every 15 • Arrest disorder – complete cessation of progress
the first stage minutes • No dilation for 4 hours
If at risk Every 15 minutes Every 5 minutes
Maternal Monitoring
Temp, pulse, BP At least every 4 hours

Others
Oral intake Gastric emptying time is remarkably prolonged
once labor is established and analgesics are
administered
ACOG: oral intake of moderate amounts of clear
liquids is reasonable if uncomplicated labor
IVF Glucose, sodium and water to fasting women at a
rate of 60-120ml/hr prevents dehydration and
acidosis
Maternal Lying supine is avoided to avert aortocaval
position compression and its potential to lower uterine
perfusion
Rupture of Fetal head must be well applied to the cervix and
membranes not be dislodged to avoid cord prolapse
Urinary Risk factors for retention: primiparity, oxytocin
bladder induced or augmented labor, perineal lacerations,
function operative vaginal delivery, catheterization during
labor and labor duration > 10 hours
Obstetric Care Consensus Committee Recommendations
1. Prolonged latent phase is not an indication for CS
2. If labor is progressive but slow → do not CS immediately
instead observe, assess and stimulate contractions as
needed
3. Cervical dilatation of 6cm is now the recommended
threshold
4. CS for active phase arrest should be reserved for women at
or beyond 6cm of dilation with ruptured membranes who
fail to progress despite 4 hours of adequate uterine
activity or at least 6 hours of oxytocin administration with
inadequate contractions and no cervical change

65
Second Stage Descent Disorders:
• Disproportion of the fetus and pelvis becomes apparent Transverse Lie
during the second stage • When the long axis forms an acute angle – oblique lie
• Nulliparas: limited to 2 hours and extended to 3 hours • Shoulder is usually positioned over the pelvic inlet
when regional analgesia is used • Women with >4 deliveries – tenfold incidence of
• Before arrest in second stage is called: transverse lie
o Nulliparas: allow to push for at least 3 hours • Causes:
o Multiparas: allow to push for at least 2 hours o Abdominal wall relaxation from high parity
o Preterm fetus
Fetal Station at Labor Onset: o Placenta previa
• A higher station at the onset of labor is significantly linked o Abnormal uterine anatomy
with subsequent dystocia o Hydramnios
Risks for Uterine Dysfunction o Contracted pelvis
• Chorioamnionitis is associated with prolonged labor
• Maternal intrapartum infection contributes to abnormal Compound Presentation:
uterine activity • Serious injury to the forearm is rare

PRECIPITOUS LABOR AND DELIVERY COMPLICATIONS WITH DYSTOCIA

• May results from an abnormally low resistance of the soft Maternal Complications:
parts of the birth canal • Infection: either intrapartum chorioamnionitis or
• Abnormally strong uterine and abdominal contractions postpartum pelvic infection is more common with
• Expulsion of the fetus in less than 3 hours desultory and prolonged labors
• Frequently followed by uterine atony • Postpartum hemorrhage: atony with increased and
prolonged and augmented labors
FETOPELVIC DISPROPORTION • Uterine tears with hysterectomy: if fetal head is impacted
Pelvic Capacity in the pelvis
Contracted inlet • Before labor, fetal biparietal diameter • Uterine rupture
averages from 0.5-9.8cm • Fistula formation: when presenting part is firmly wedged
• If AP is <10cm → contracted inlet into the pelvic inlet and tissues of the birth canal are
Contracted midpelvis • When sum of the interspinous and subjected to excessive pressure → impaired circulation,
necrosis and may become evident several days after
posterior sagittal diameters of midpelvis
delivery → vesicovaginal, vesicocervical or rectovaginal
(normally 10.5 + 5 or 15.5cm) falls below
fistula
13.5cm or
• Pelvic floor injury: when exposed to direct compression
• When interspinous diameter is <10cm
from the fetal head and to downward pressure from
Contracted outlet • Interischial tuberous diameter of 8cm or
maternal expulsive efforts
less
• Lower extremity nerve injury: common fibular (common
peroneal) nerve from inappropriate leg positioning in
Pelvic Fractures
stirrups
• Trauma from automobile collisions – most common cause
o Symptoms resolve within 6 months
• In determining suitability for vaginal delivery, fracture
healing requires 8-12 weeks and a recent fracture merits
cesarean delivery CHAPTER 24
Face Presentation:
• Mentum posterior presentation is undeliverable except
with a very preterm fetus Intrapartum Assessment
• Fetal malformations and hydramnios – risk factors
• Anencephaly also presents by the face Electronic Fetal Monitoring
• Extended neck positions develop more frequently when
pelvis is contracted, or the fetus is very large Internal (Direct) Electronic Attaching a bipolar spiral
• High parity – predisposing factor Monitoring electrode directly to the fetus
• Cardinal movements of descent, internal rotation and External (Indirect) Electronic Fetal HR is detected through the
flexion and the accessory movements of extension and Monitoring maternal abdominal wall using
external rotation ultrasound doppler principle
Brow Presentation: FHR patterns 30 beats per minute per vertical
• Often converts to a face or occiput presentation cm and 3cm/min chart recorder
paper speed

66
Baseline Fetal Heart Activity
Rate:
• With increasing fetal maturation, the heart rate decreases
• Baseline fetal heart rate declined an average of 24bpm
between 16 weeks or approximately 1bpm per week
• The decrease corresponds to maturation of
parasympathetic heart control
• Average fetal HR is considered the result of tonic balance
between accelerator and decelerator influences on
pacemaker cells
• Bradycardia: causes include congenital heart block and
serious fetal compromise
• Tachycardia: most common – maternal fever from
chorioamnionitis
o Stoles Other causes: fetal compromise, cardiac
arrythmias, maternal administration of
parasympathetic inhibiting (atropine) or
sympathomimetic (terb) drugs
• Wandering Baseline: neurologically abnormal fetus may
occur as a preterminal event
Beat to Beat Variability:
• Important index of CV function
• Regulated largely by the ANS → sympathetic and
parasympathetic
• Short term variability: instantaneous change in fetal heart
Periodic Fetal HR Changes
rate from one beat or R wave to the next
o Measure of the time interval between cardiac
systoles
• Increased Variability: accompanied fetal breathing and
body movements
• Decreased Variability: administration of analgesic drugs
during labor
o Variability regularly diminishes within 5-10
minutes following meperidine
o Magnesium sulfate: no evidence of adverse
neonatal effects
o Fetal acidemia: loss of variability with
decelerations
o Caused by metabolic acidemia that causes
depression of the fetal brainstem or heart itself
o Reduced baseline HR variability is the single most
reliable sign of fetal compromise
o Diminished variability maintained for 1 hour was
diagnostic of developing acidemia and imminent
fetal death
o Decreased variability in the absence of
decelerations is unlikely to reflect fetal hypoxia
• Absent variability: reflects previous fetal insult that has
resulted in neurological damage
• Cardiac Arrhythmias: can only be detected when scalp
electrodes are used
o Intermittent baseline bradycardia: frequently
due to a congenital heart block
• Sinusoidal HR:
o May be due to:
▪ Fetal intracranial hemorrhage
▪ Severe fetal asphyxia
▪ Severe fetal anemia (anti-D
alloimmunization, fetomaternal
hemorrhage, TTSS, fetal parvoviral
infection or vasa previa with bleeding)
▪ Meperidine, morphine, alphaprodine
and butorphanol
o Stable baseline HR of 120-160bpm with regular
oscillations
o Amplitude of 5-15bpm
o Long term variability frequency of 2-5 cycles per
minute
o Fixed or flat short term variability
o Oscillation of the sinusoidal waveform above or
below a baseline
o Absent accelerations
o Pseudosinusoidal: sine wavelike baseline
variation with periods of acceleration
▪ Fetal sucking or transient episodes of
fetal hypoxia caused by umbilical cord
compression
• Deviations from baseline that are temporally related to
uterine contractions
• Acceleration: abrupt heart rate increases above the fetal
heart rate baseline and defined by an onset to peak rise
within 30 seconds
o 32 weeks and beyond: acceleration has a peak
>15bpm above baseline >15 seconds but <2
minutes from onset
o Before 32 weeks: >10 bpm for 10 seconds to 2
minutes is normal, prolonged is >2 minutes but
<10 minutes
o Proposed mechanisms for accelerations:
▪ Fetal movement
▪ Stimulation by uterine contractions
▪ Umbilical cord occlusion
▪ Fetal stimulating during pelvic
examination
▪ Scalp blood sampling
▪ Acoustic stimulation
• Early Deceleration: seen in active labor between 4-7cm
cervical dilatation
o Head compression → vagal nerve activation (as a
result of dural stimulation) → deceleration
• Late Deceleration: interval or lag from the contraction
onset until the late deceleration onset directly related to
basal fetal oxygenation
o Length of lag was predictive of fetal oxygenation
not fetal pH
o First fetal HR consequence of uteroplacental
induced hypoxia
o Any process that produces maternal
hypotension, excessive uterine activity or
67
 placental dysfunction can induce late Fetal Electrocardiography:
deceleration • An elevated ST segment and a progressive rise in T-wave
o 2 most common sources: height (T:QRS ratio)
▪ Hypotension from epidural • Increasing T:QRS ratios are thought to reflect fetal cardiac
▪ Uterine hyperactivity from oxytocin ability to adapt to hypoxia and appear before neurological
• Variable Deceleration: most frequent deceleration damage
patterns encountered during labor NON-REASSURING FETAL STATUS
o Attributed to: umbilical cord occlusion
o Decrease must last between 15 seconds and 2 Three-Tier Fetal Heart Rate Interpretation System:
minutes and must be >15 bpm in amplitude
o Vagal response may be due to chemoreceptor or
baroreceptor activity or both
o Represent fetal heart rate reflexes that reflect
either blood pressure changes due to
interruption of umbilical flow or changes in
oxygenation
• Saltatory baseline HR: rapidly recurring couplets of
acceleration and deceleration
o Do not signal fetal compromise
• Lambda pattern: involves an acceleration followed by a
variable deceleration with no acceleration at the end of
the deceleration
o Seen during: early labor and is not ominous
o May result from: mild cord compression or
stretch
• Overshoot: variable deceleration followed by acceleration
• Prolonged deceleration: an isolated deceleration >15bpm
that lasts >2 minutes but <10 minutes from onset to return
to baseline
o Causes: maternal hypoperfusion or hypoxia from
any cause, placental abruption, umbilical cord
knots or prolapse, maternal seizures including
eclampsia and epilepsy, application of a fetal
scalp electrode, impending birth or maternal
Valsalva maneuver

FHR Patterns During Second Stage Labor

• Abnormal baseline heart rate in the presence of deep
second stage decelerations is associated with a greater risk
for fetal compromise

Other Intrapartum Assessment Techniques

Fetal Scalp Blood Sampling
• May help identify the fetus in serious distress but not
predictive of neonatal outcome
pH Management
>7.25 Labor is observed
7.20-7.25 Repeat pH measurement within
30 minutes
<7.20 Collect another scalp blood
sample
• Benefit: fewer CS for fetal distress
• Unnecessary!

Vibroacoustic Stimulation:
• Normal if a fetal HR acceleration of at least 15bpm for at
least 15 seconds occur within 15 seconds after the
stimulation and with prolonged fetal movements
Fetal Pulse Oximetry
• The lower limit for neonatal fetal O2 sat: 30%
Meconium in the Amnionic Fluid
• Fetuses may pass meconium in response to hypoxia
• Signals fetal compromise
• Meconium aspiration syndrome was significantly
associated with fetal acidemia at birth
68
 • Fetal hypercarbia → stimulates fetal respiration → • Uterine contractions are clinically palpable only after their
aspiration of meconium into the alveoli intensity exceeds 10mmHg
• Lung parenchymal injury is secondary to acidemia-induced • Until the intensity of contractions reaches 40mmHg, the
alveolar cell damage uterine wall can readily be depressed by the finger
• Uterine contractions not associated with pain until their
strength exceeds 15mmHg → minimum pressure required
to distend the lower uterine segment and cervix
Resuscitative Measures for Category II or III Tracings:
Fetal HR Abnormality Interventions
Recurrent late Lateral decubitus
decelerations Maternal oxygen Origin and Propagation of Contractions
Prolonged IV hydration • Contractions spread from the pacemaker area throughout
decelerations or Reduce uterine contraction frequency the uterus at 2cm/sec and the whole organ is depolarized
bradycardia within 15 seconds
Minimal or absent FHR • Depolarization propagates downward toward the cervix
variability • Intensity is greatest in the fundus
Tachysystole with Cat II Discontinue oxytocin or prostaglandins
or III tracing Give tocolytics: terb, mag sulfate Uterine Contraction Terminology
Recurrent variable Reposition mother • Normal uterine activity: five or fewer contractions in 10
decelerations Amnioinfusion minutes, averaged during a 30-minute span
Prolonged With cord prolapse → manual elevate • Tachysystole: more than 5 contractions in 10 minutes,
decelerations or presenting part while preparing for averaged over 30 minutes
bradycardia immediate delivery

Management Options:
CHAPTER 25
Tocolysis
• Terbutaline sulfate can be a temporizing maneuver in the Obstetrical Analgesia and Anesthesia
management of NRHRP
• 250 ug IV or subcutaneous • 0.2% of maternal deaths attributed to anesthesia
Amnioinfusion complications
• Reasonable approach in treatment of repetitive variable • Most significant factor linked to lower maternal mortality
decelerations regardless of meconium status rates is the greater use of regional anesthesia
• For oligohydramnios: used prophylactically to avoid General Principles:
intrapartum fetal heart rate patterns from cord occlusion • A woman’s request for labor pain relief is sufficient
• Not recommended to dilute meconium stained AF medical indication for its provision
Maternal Factors that may Prompt Anesthetic Consultation (BODS
Fetal HR Patterns and Brain Injury BOTS Ma Pre)
• Umbilical cord blood gasses should be obtained when CS is Body mass index >30kg/m2
performed for fetal compromise Obstructive lesions: edema, anatomical abnormalities, trauma
Decreased range of motion in mouth or small mandible
Benefits of Electronic FHR Monitoring Short or thick neck or skeletal neck abnormality
• Early detection of the compromised fetus
Bleeding disorders
Guidelines for Methods of Intrapartum FHR Monitoring Obstetrical complications with high risk of operative delivery
Thyromegaly or other neck tumor
Surveillance Low Risk High Risk Severe preeclampsia
Acceptable methods
Intermittent Yes Yes Maternal medical complications (cardiopulmonary disease)
auscultation Previous anesthetic complications
Continuous Yes Yes
electronic fetal Pain Relief Principles:
monitoring • The sympathetic nervous system response to pain →
Evaluation Intervals marked elevation in circulating catecholamines → affects
First stage labor 30 minutes 15 minutes uterine activity and uteroplacental blood flow
(active)
Second stage labor 15 minutes 5 minutes

Patterns of Uterine Activity

• Clinical labor usually commences when uterine activity
reaches values between 80-120 MVU

69
 Analgesia and Sedation during Labor
Management of Local Anesthetic Systemic Toxicity
Agent Dose Remarks • Benzodiazepine (midazolam, lorazepam) to control
Parenteral Agents seizures if lipid emulsions are not available
Meperidine and Meperidine: 50- Analgesia maximal • Magnesium sulfate
Promethazine 100mg + 30-45 minutes after • Best for the fetus and mother to delay delivery until
promethazine 25mg IM mother is stabilized
Meperidine: most IM at intervals of 2-5 Pudendal Block:
common opioid hours Readily crosses How to do it:
used worldwide for placenta and can 1. Needle is advanced until it touches the sacrospinous
pain relief during 25-50mg IV every 1- have prolonged half- ligament → infiltrate with 3ml of lidocaine
labor 2 hrs life in newborn 2. Needle is advanced farther through the ligament
Butorphanol: 1-2mg IV Major SE: 3. As needle pierces loose areolar tissue behind the ligament,
synthetic opioid somnolence, resistance against the plunger drops → push another 3ml
receptor agonist- dizziness, dysphoria 4. Needle is withdrawn into the introducer which is moved to
antagonist analgesic Associated with a point just above the ischial spine
transient sinusoidal 5. Needle is inserted through the mucosa and a final 3ml id
FHR patterns deposited
Nalbuphine: mixed IM, IV or SC 6. Repeat on the other side
opioid receptor 10-20mg every 4-6 Within 3-4 minutes, a successful pudendal block will allow pain relief
agonist-antagonist hours ANATOMY REVIEW!
Fentanyl: short 50-100 ug IV every Short duration of • Pain with vaginal delivery arises from stimuli from the lower
acting and potent hour action → requires genital tract
synthetic opioid frequent dosing or • Transmitted through the pudendal nerve peripheral branches
PCA (provides sensory innervation to the perineum, anus, vulva and
Remifentanil: Half-life: 3.5 minutes Quickly metabolized clitoris) → passes through sacrospinous ligament just as the
synthetic opioid with or redistributed ligament attaches to the ischial spine
an extremely rapid within the fetus → • Sensory nerve fibers of the pudendal nerve are derived from
onset of action ready naloxone at ventral branches of S2-S4
birth
Nitrous Oxide: Paracervical Block
Rapid onset and offset • Provides satisfactory pain relief during first stage of labor
Mixture of 50% NO and 50% O2 in a single cylinder • 5-10ml of lidocaine or chloroprocaine is injected into the
Inhaled 30 seconds prior to the start of a contraction cervix laterally at 3 and 9 o’clock
Associated with N/V • May cause drug-induced arterial vasospasm
*Naloxone contraindicated in narcotic-addicted mothers • Not used in situations of potential fetal compromise

REGIONAL ANALGESIA NEURAXIAL ANALGESIA

Anesthetic Agents
• Dilute epinephrine is sometimes added and given as a test
dose due to systemic toxicity from local anesthesia
• A sudden significant rise in maternal HR or BP after
administration suggests IV catheter placement
CNS toxicity:
• Early symptoms are those of stimulation → depression
• Light headedness
• Dizziness
• Tinnitus
• Metallic taste
• Numbness of tongue and mouth
• Slurred speech
• Muscle fasciculation and excitation
• Generalized convulsions → loss of consciousness
Cardiovascular Toxicity
• Bupivacaine – associated with neurotoxicity and
cardiotoxicity at identical levels
• Use of a 0.75% solution for epidural injection
• Hypertension, tachycardia → hypotension, cardiac
arrythmias and impaired uteroplacental perfusion
Spinal (Subarachnoid Block)
• Rapid analgesia onset
• Short duration of action
• High success rate
• Subarachnoid space during pregnancy is smaller due to
internal vertebral venous plexus engorgement
Vaginal delivery:
• Requires sensory block to the level of the umbilicus (T10)
• Operative delivery: sensory block of S2-S4 is adequate
• SE: pruritus, urinary retention
Cesarean delivery:
• Sensory blockade extending to the T4 dermatome is
desired
• 10-12mg of bupivacaine in a hyperbaric solution
• 50-75 mg of lidocaine hyperbaric solution
• Addition of opioid increases rapidity of blockade onset,
reduces shivering and minimizes referred pain and other
symptoms such as N/V

70
Complications:
Complication Cause Management
Hypotension From Left lateral, IV crystalloid Absolute Contraindications to Neuraxial Analgesia
vasodilatation hydration, bolus of ephedrine or (HI TRUMP)
from phenylephrine Heparin (low molecular weight) within 12 hours
sympathetic Ephedrine: Infection over site of needle placement
blockade and is • Sympathomimetic drug that
compounded by binds to alpha and beta Thrombocytopenia
obstructed receptors and enhances Refractory maternal hypotension
venous return norepinephrine release Untreated maternal bacteremia
due to uterine • Raises blood pressure by Maternal coagulopathy
compression of raising HR and CO and Pressure (intracranial) increased by a mass lesion
the great vessels elevating PVR
Phenylephrine: EPIDURAL ANALGESIA
• Pure alpha agonist and • Injection of a local anesthetic agent into the epidural or
elevates blood pressure peridural space
through vasoconstriction o Space contains areolar tissue, fat, lymphatics and
High or total Follows • Uterus is displaced laterally internal vertebral venous plexus → becomes
spinal administration to minimize aortocaval engorged during pregnancy → volume of the
blockade of an excessive compression epidural space is reduced
dose of local • Effective ventilation with • Entry for obstetrical analgesia is through a lumbar
anesthetic or tracheal intubation intervertebral space
inadvertent • IV vasopressors
injection into CONTINUOUS LUMBAR EPIDURAL BLOCK
the subdural or • Complete analgesia for the pain of labor and vaginal
subarachnoid delivery necessitates a block from the T10 to the S5
space dermatomes
Postdural • Leakage of • Epidural blood patch: gold • CS delivery: a block extending from the T4 to S1
puncture CSF from the standard (10-20ml of dermatome is desired
headache dura mater autologous blood obtained • Observe for features of toxicity from IV injection: signs of
puncture site aseptically is injected into high or total blockade from subdural or subarachnoid
• When the epidural space) injection → if none → full dose is given
woman sits Complications:
or stands, Complication Cause
the Higher or total spinal Dural puncture with inadvertent
diminished blockade subarachnoid injection
CSF volume
creates
Ineffective Analgesia More likely to fail as BMI increased
traction on
pain- Hypotension Sympathetic blockade from epidurally
sensitive CNS injected analgesic agents can cause
hypotension and decreased CO
Convulsions • Temporary • Blood patch Maternal fever • Alteration of the hypothalamic
blindness thermoregulatory set point
and • Impairment of peripheral
convulsions thermoreceptor input to the CNS
Bladder • Bladder • Observe with selective blockage of warm
dysfunction sensation is stimuli
likely to be • Imbalance between heat production
obtunded and loss
and bladder Back pain • Persistent pain uncommon
emptying is
impaired for Effects on labor:
several hours • Epidural analgesia prolongs labor and increases use of
Arachnoiditis • Rare • oxytocin stimulation
and • Increased need for operative vaginal delivery because of
Meningitis prolonged second stage
• Impaired maternal expulsive efforts
71
 • Does not significantly raise cesarean delivery rates • Ketamine – avoided in hypertensive patients
• Timing has no effect on the risk of CS, forceps or fetal • Succinylcholine as muscle relaxation
malposition • Sellick maneuver – cricoid pressure applied
• Surgery should only begin only after an airway is secured
Failed intubation
• Morbid obesity is a major factor

Contraindications:
• Thrombocytopenia Inhalational Anesthetics:
Platelet count Anesthesia • Desflurane and sevoflurane – both have low solubility in
80,000-100,000 Regional anesthesia blood and fat
50,000-80,000 Spinal anesthesia Aspiration
• Fasting:
• Anticoagulation o Right mainstem bronchus has the simplest
o If on unfractionated heparin → normal PTT pathway for aspirated material to reach the lung
o If prophylactic dose of unfractionated heparin + parenchyma
low dose aspirin → not at an increased risk → o Right lower lobe is most often involved
regional anesthesia
o Once daily, low dose low molecular weight
heparin → must be 12 hours apart
CHAPTER 26
o LMWH should be withheld for at least 2 hours
after epidural catheter removal Induction and Augmentation of Labor
o Women who receive LMWH 2x a day –
insufficient studies Induction: stimulation of contractions before spontaneous onset of
• Severe preeclampsia-eclampsia labor with or without ruptured membranes
o Hypotension and hypertension from pressor Augmentation: enhancement of spontaneous contractions that are
agents to correct hypotension considered inadequate because of failed cervical dilation and fetal
o Pulmonary edema follows descent
o GA can lead to severe sudden hypertension →
pulmonary or cerebral edema or intracranial LABOR INDUCTION
hemorrhage INDICATIONS:
o Aggressive volume replacement increases risk for • Membrane rupture without labor
pulmonary edema (due to: extravascular volume • Gestational hypertension
is increased due to capillary leak caused by
• Oligohydramnios
endothelial cell activation)
• Nonreassuring fetal status
o Vasodilation produced by epidural block is less
• Post term pregnancy
abrupt if analgesia level is achieved slowly with
• Maternal medical conditions – chronic hypertension and
dilute solutions of local anesthetic agents
diabetes
CONTRAINDICATIONS:
COMBINED SPINAL EPIDURAL ANALGESIA
• Prior uterine incision type
• Needle through needle technique
• Contracted or distorted pelvic anatomy
• Local anesthetic is injected into the subarachnoid space →
• Abnormally implanted placenta
spinal needle withdrawn → epidural catheter is placed
• Active genital herpes
• Cervical cancer
LOCAL INFILTRATION FOR CESAREAN DELIVERY
• Appreciable macrosomia
• Total of 70ml 0.5% lidocaine with 1:200,000 epinephrine is
• Severe hydrocephalus
prepared
• Malpresentation
• Field block of the major branches supplying the abdominal
wall – 10th, 11th and 12th intercostal nerves and the • NRFS
ilioinguinal and genitofemoral nerves TECHNIQUES:
• Oxytocin
GENERAL ANESTHESIA • Prostaglandins
• Mechanical methods
• Common cause of death: failed intubation
RISKS:
Patient Preparation
• CS
• Antacid (H2 receptor antagonist – metoclopramide)
• Lateral uterine displacement • Chorioamnionitis
• Preoxygenation done • Uterine rupture
Induction and Intubation • PPH from uterine anatomy
• IV propofol or etomidate is widely used and offers rapid • Labor induction: 2-3fold greater risk for CS
induction • Amniotomy to augment labor → higher risk for
• Quick onset and recovery with lower rates of nausea and chorioamnionitis
vomiting
72
 • ACOG – against the use of prostaglandins for preinduction • ACOG recommends fetal heart rate and uterine
cervical ripening or labor induction in women with a prior contraction monitoring
uterine incision IV OXYTOCIN
FACTORS AFFECTING INDUCTION SUCCESS: • Goal: to effect uterine activity sufficient to produce
• Younger age cervical change and fetal descent while avoiding
• Multiparity development of NRFS
• BMI <30 • When oxytocin is stopped → concentration in plasma
• Favorable cervix rapidly falls (because half-life is only 3-5 minutes)
• BW: <3500 g DOSAGE
Preinduction Cervical Ripening • 1ml contains 10 units → 10-20 mU/mL
• Pharmacological and mechanical methods to enhance OXYTOCIN REGIMENS:
cervical favorability • Dublin protocol: start at 6mU/min and advanced in
Cervical Favorability: 6mU/min increments
• Bishop score of 9 = high likelihood for a successful INTERVAL BETWEEN INCREMENTAL DOSING
induction • Vary from 15-40 minutes
• BS <4: unfavorable cervix and an indication for cervical MAXIMAL OXYTOCIN DOSAGE
ripening • Greater than 48mU/min has no apparent risk
BISHOP SCORE (DESCO PO) RISK VS BENEFITS
Score Dilation Effacement Station Consistency Position • Oxytocin has amino-acid homology similar to vasopressin
0 Closed 0-30 -3 Firm Posterior • When infused at 20mU/min or more → renal free water
1 1-2 40-50 -2 Medium Mid clearance drops → water intoxication → can lead to
convulsions, coma and death
2 3-4 60-70 -1 Soft Anterior
• Better to increase concentration rather than increasing the
3 >5 >80 +1,+2
flow rate
Prostaglandin E2
AMNIOTOMY FOR INDUCTION AND AUGMENTATION
• Dinoprostone – synthetic analogue of prostaglandin E2
(PGE2) • Elective Amniotomy: at approx. 5cm dilation =
acceleration in spontaneous labor by 1 – 1/12 hours
• Available in gel, time release or a 20mg suppository
• For labor induction: surgical induction, amniotomy alone
• Doses may be repeated every 6 hours max of 3 doses
or combined with oxytocin was superior to oxytocin alone
• Side effects:
• For labor augmentation: when labor is abnormally slow
o Uterine tachysystole >5 contractions in 10
o Risk: increased incidence of chorioamnionitis
minutes
• Irrigation to remove the gel has not been shown to be
helpful CHAPTER 27
• Contraindications:
o History of dinoprostone hypersensitivity
o Suspicion of fetal compromise Vaginal Delivery
o CPD PREPARATION FOR DELIVERY
o Unexplained vaginal bleeding • Increased perineal pressure from the fetal head creates
o Already on oxytocin reflexive bearing down efforts which are encouraged when
o Those with >6 previous term pregnancies appropriate
o Contraindication to vaginal delivery OCCIPUT ANTERIOR POSITION
o Contraindication to oxytocin use (like a previous Delivery of the head:
uterine surgery) • Crowning: encirclement of the largest head diameter by
the vulvar ring
Prostaglandin E1 • Slow delivery of the head may decrease lacerations
• Misoprostol • Modified ritgen maneuver: gloved fingers beneath a
• Vaginally administered offer equivalent or superior draped towel exert forward pressure on the fetal chin
efficacy through the perineum just in front of the coccyx
o Moderate upward pressure is applied to the fetal
Mechanical Techniques chin by the posterior hand covered by a sterile
• Transcervical catheter – only when the cervix is towel
unfavorable o Other hand applies occipital pressure
Delivery of the shoulders:
METHODS OF INDUCTION AND AUGMENTATION • Hooking the fingers in the axillae is avoided! Since this can
Prostaglandin E1 injure upper extremity nerves and produce a transient or
• 100 ug oral or 25ug vaginal misoprostol has similar efficacy possibly permanent paralysis
with IV oxytocin Cord Clamping
OXYTOCIN • A delay for up to 60 seconds may increase total body iron
• Its use in augmentation is a key component in the active stores, expand blood volume and decrease anemia
management of labor incidence

73
 • Higher hgb concentration increases risks for
hyperbilirubinemia and extended hospitalization for
neonatal phototherapy
• Preterm neonate benefits of delayed cord clamping:
o Higher red cell volume
o Decreased need for BT
o Lower rates of IVH and necrotizing enterocolitis
• ACOG: delay for at least 30-60 seconds after birth
OCCIPUT TRANSVERSE POSITION
• Use of Kielland forceps for persistent OT position
Persistent Occiput Posterior Position
• 2-10% of singleton term cephalic fetuses delivery in OP
• Predisposing risks:
o Epidural analgesia
o Nulliparity
o Greater fetal weight
o Prior delivery with OP position
Morbidity:
• Higher associated rates of:
o Prolonged 2nd stage labor
o CS
o Operative delivery
• Associated with adverse short term neonatal outcomes:
o Academic umbilical cord gases
o Birth trauma
o APGAR <7
o ICU admission
Delivery:
• Associated with higher rates of 3rd and 4th degree
lacerations as the head is driven against the perineum to a
much greater degree than when the head position is in OA
Shoulder Dystocia
• A head-to-body delivery time >60 seconds
Maternal and Neonatal Consequences:
• Greater risk to the fetus than the mother
• Main maternal risks: serious perineal tears and PPH from
uterine atony
• Neonatal neuromusculoskeletal injury and asphyxia
Prediction and Prevention:
• Most cases cannot be accurately predicted or prevented
• Elective induction of labor or elective CS for all women
suspected of having a macrosomic fetus is not appropriate
• Planned CS may be considered for the nondiabetic woman
with a fetus >5000g or diabetic mother whose fetus is
>4500g
Prior Shoulder Dystocia:
• Risk of recurrent shoulder dystocia: 1-13%
Management:
• Goal is to reduce head-to-body delivery time
• Large episiotomy
• Moderate suprapubic pressure can be applied by an
assistant while downward traction is applied to the fetal
head
• McRoberts maneuver – suprapubic pressure concurrently
applied with removing legs from stirrups and sharply
flexing the up toward the abdomen
o Straightens the sacrum relative to the lumbar
vertebrae, rotation of the symphysis pubis
toward the maternal head and a decrease in the
angle of pelvic inclination
• Woods corkscrew maneuver: progressively rotating the
posterior shoulder 180 degrees in a corkscrew fashion =
impacted anterior shoulder release
• Rubin’s maneuver:
o Fetal shoulders are rocked from side to side by
applying force on the maternal abdomen
o If not successful → pelvic hand reaches the most
accessible fetal shoulder which is then pushed
toward the anterior surface of the chest → this
abducts both shoulders → smaller bisacromial
diameter → permits displacement of the
anterior shoulder form behind the symphysis
• Gaskin maneuver: all fours
o Downward traction against the head and neck
attempts to free the posterior shoulder
• Deliberate fracture of the anterior clavicle using the thumb
to press it toward and against the pubic ramus can be
attempted to free the shoulder impaction
• Zavanelli maneuver: replacement of fetal head into the
pelvis followed by CS
• Symphysiotomy: intervening the symphyseal cartilage and
its ligamentous support is cut to widen symphysis pubis
o Maternal morbidity due to urinary tract injury
• Cleidotomy: cutting the clavicle with scissors or other
sharp instruments and is usually done for a dead fetus
Shoulder Dystocia Drill
1. Call for help, drain the bladder
2. Generous episiotomy
3. Suprapubic pressure is used initially by most practitioners
because it has the advantage of simplicity
4. McRoberts (2 assistants needed)
If this fails:
5. Delivery of the posterior arm is attempted
6. Woods screw maneuver
7. Rubin maneuver
Special Populations
Home Birth:
• Contraindicated: prior CS, breech, multifetal gestation
Female Genital Mutilation
• Deinfibulation: division of midline scar tissue to reopen
the vulva
Anomalous Fetuses
• Hydrocephalus:
o Mild and biparietal diameter <10cm or tie head
circumference may be permitted vaginal delivery
THIRD STAGE OF LABOR
Delivery of the Placenta:
• Goals: delivery of an intact placenta and avoidance of
uterine inversion or postpartum hemorrhage
74
 • To prevent uterine inversion, UC traction must not be used 3C EAS and IAS are torn
to pull the placenta from the uterus 4th degree Perineal body, entire anal
• Signs of separation: sphincter complex,
o Globular and firmer fundus anorectal mucosa
o Lengthening of the cord
o Sudden gush of blood Risk Factors for 3rd and 4th degree:
o Elevation of the uterus into the abdomen • Nulliparity
• Range: 4-12 minutes • Midline episiotomy
Management of the Third Stage: • Persistent OP position
• Expectant or active • Operative vaginal delivery
• Expectant: waiting for placental separation, signs and • Asian race
allowing placenta to deliver either spontaneously or aided • Short, perineal length
by nipple stimulation • Increasing fetal BW
• Active management: early cord clamping, controlled cord
traction, immediate administration of prophylactic Episiotomy:
oxytocin → goal is to limit PPH • Incision of the pudendum – the external genital organs
o Carbetocin: long acting oxytocin analogue • Midline: begins at fourchette, incises the perineal body in
o Uterotonics may be given before or after the midline and ends before the EAS is reached
placental expulsion without affecting rates of o Length: 2-3cm depending on perineal length
PPH, placental retention or 3rd stage labor length o Associated with: anal sphincter lacerations
o High dose Oxytocin: when given as a bolus can • Mediolateral: begins at midline of the fourchette and is
cause profound hypotension directed to the right or left at an angle 60 degrees off the
▪ Should be given as a dilute solution by midline
continuous intravenous infusion • Lateral: begins at point 1-2cm lateral from the midline
▪ 20 units in 1L of infusate • Analgesia: bilateral pudendal nerve block or local
o Other uterotonics: infiltration of 1% lidocaine, EMLA cream (but must be
▪ Methylergonovine: CI in hypertensive applied at least 1 hr before)
woman Indications:
• Manual Removal of Placenta: • Restrict use of episiotomy
o Placenta adherent in which uterine contractions
• Consider if with:
are insufficient to detach the placenta
o Shoulder dystocia
o Lower uterine segment constriction
o Breech delivery
o Detached but trapped placenta
o Fetal macrosomia
o Morbidly adherent placenta
o Operative gain deliveries
• Risks for retained placenta: o Persistent OP positions
o Stillbirth o Markedly short perineal length
o Prior CS delivery Repair:
o Prior retention and preterm delivery
• Use of 2-0 polyglactin (Vicryl): decrease in postsurgical
• WHO cites a 60-minute threshold pain and lower risk of wound dehiscence
• Fourth degree: 4-0 polyglactin or chromic gut for anal
IMMEDIATE POSTPARTUM CARE mucosa
• PPH due to atony is most likely at this time • Single dose of antibiotic at the time of repair is
• Maternal BP and pulse recorded after delivery every 15 recommended
minutes for the first 2 hours • A single dose of 2nd generation cephalosporin is suitable or
clindamycin for penicillin allergic women
BIRTH CANAL LACERATIONS • With OASIS: stool softeners for a week (avoid enemas and
suppositories)
Perineal Layers traversed Perineal Laceration Care:
Laceration • 2nd degree lacerations or AS tears: intercourse is
1st degree Vaginal epithelium, proscribed until after the first visit at 6 weeks
perineal skin • If with perineal trauma → 3-6 months
2nd degree Perineum that spares the
anal sphincter complex but
involves the perineal CHAPTER 28
muscles – Bulbospongiosus
and superficial transverse
Breech Delivery
perineal muscles CLASSIFICATION OF BREECH PRESENTATIONS
3rd degree
Presentation Description On IE
3A <50% of internal anal Considered
Frank Breech Lower extremities are flexed at No feet are
sphincter is torn Obstetrical Anal
the hips and extended at the appreciated.
3B >50% of EAS is torn but IAS Sphincter Injuries knees (feet lie close to the head) Fetal ischial
remains intact (OASIS)
75

Complete Both hips are flexed and one or
breech both knees are also flexed
Incomplete One or both hips are extended
breech → one or both feet or knees lie
below the breech such that a
foot or knee is lowermost in the
birth canal (ex. Footling breech)
Stargazing Extremely hyperextended neck – 5%
fetus
Flying fetus Transverse lie with hyperextension of the fetal neck
tuberosities, sacrum • Total breech extraction: entire fetal body is extracted by
and anus are the provider
palpated
Feet may be felt Spontaneous Breech Delivery
alongside the butt
Feet palpated • Engagement and descent of the breech usually take place
with the bictrichanteric diameter in one of the oblique
pelvic diameters
• Anterior hip usually descends more rapidly than the
posterior hip → when resistance of pelvic floor is met →
internal rotation of 45 degrees follows to bring anterior
hip toward the pubic arch → bitrochanteric diameter will
occupy the AP diameter of pelvic outlet

DIAGNOSIS
Risk Factors:
• Early gestational age Partial Breech Extraction
• Extremes of amnionic fluid volume
• Ideally, breech is allowed to delivery spontaneously to the
• Multifetal gestation
umbilicus
• Hydrocephaly
• Following delivery of the legs → fetal bony pelvis is
• Anencephaly
grasped with both hands, fingers resting on the ASIS and
• Structural uterine abnormalities
thumbs on the sacrum
• Placenta previa
• Employ steady, gentle, downward traction until the lower
• Pelvic tumors halves of the scapulas are delivered, making no attempt at
• Prior breech delivery → recurrence was 10% and third delivery of the shoulders and arms until on axilla becomes
breech: 28% visible
Delivery of the Aftercoming Head:
PRETERM BREECH FETUS • Mauriceau maneuver: index and middle finger of one
• Planned cesarean delivery confers a survival advantage hand are applied over the maxilla to flex the head while
compared with planned vaginal delivery the fetal body rests of the palm of the same hand
• Higher neonatal mortality rates if vaginal o gentle suprapubic pressure simultaneously
• Consideration for CS for periviable fetuses at 23 weeks applied by an assistant helps keep the head
with a recommendation for CS at 25 weeks flexed
• Vaginal breech delivery is reasonable if fetal weight is • Forceps: piper forceps may be applied effectively when
>2500 grams Mauriceau cannot be accomplished easily
FACTORS FAVORING CS OF THE BREECH FETUS • Modified Prague Maneuver: 2 fingers of one hand grasp
• Lack of operator experience the shoulders of the backdown fetus from below while the
• Patient request for CS other hand draws the feet up and over the maternal
• Large fetus >3800-4000 grams abdomen
• Apparently healthy and viable preterm fetus either with • Head entrapment: Dührssen incisions done: 2 o’clock, 10
active labor or with indicated delivery o’clock, infrequently 6 o’clock
• Severe fetal growth restriction o Zavanelli: to relieve intractable shoulder
• Fetal anomaly incompatible with vaginal delivery dystocia
• Prior perinatal death or neonatal birth trauma
• Incomplete or footling breech Total Breech Extraction
• Hyperextended head • Complete or Incomplete Breech:
• Pelvic contraction or unfavorable pelvic shape determined o Hand is introduced through the vagina and both
clinically or with pelvimetry fetal feet are grasped
• Prior CS o Gentle traction is applied until the hips are
delivered
LABOR AND DELIVERY MANAGEMENT
Vaginal Delivery Methods: External Cephalic Version
• Spontaneous breech: fetus is expelled entirely without any • Attempted before labor in a woman who has reached 37
traction or manipulation other than support of the weeks
newborn • Contraindicated if vaginal delivery is not an option (ex.
• Partial breech: fetus is delivered spontaneously as far as Placenta previa)
the umbilicus, but the remainder of the body is delivered o Multifetal gestation
by provider traction and assisted maneuvers with or • Relative contraindications:
without maternal expulsive efforts o Early labor
o Oligohydramnios

76
 o Ruptured membranes • Willingness to abandon OVD
o Known nuchal cord • Informed consent completed
o Structural uterine anomalies
o Fetal growth restriction MORBIDITY
o Prior abruptio Maternal Morbidity:
• Discontinued for excessive discomfort, persistently • LACERATIONS: higher rates of 3rd or 4th degree lacerations
abnormal fetal heart rate or after multiple failed attempts as well as vaginal wall and cervical lacerations
• If successful → NST is done o Early disarticulation of forceps and cessation of
• Tocolysis: to relax the uterus prior to ECV → terbutaline maternal pushing during disarticulation can also
be protective
MOXIBUSTION o Injuries more common with an occiput posterior
• Traditional Chinese medicine technique that burns a position
cigarette-shaped stick of ground Artemisia vulgaris or • PELVIC FLOOR DISORDERS:
mugwort or Moxa o Urinary incontinence
• Acupuncture point (BL 67) where stick is placed to increase o Anal incontinence
fetal movement and promote spontaneous breech version o Pelvic organ prolapse
• Done at 33-36 weeks Perinatal Morbidity
• Common risk factor for ICH is abnormal labor
• Acute injury from primary vessel laceration
CHAPTER 29 • ICH may result from skull fracture and vessel laceration or
due to exerted forces
Operative Vaginal Delivery
FETAL INDICATIONS: FORCEPS DELIVERY
• NRFHRP Design:
• Premature placental separation • Blade, shank, lock and handle
MATERNAL INDICATIONS: • True fenestration: reduces degree of head slippage during
• Heart disease forceps rotation
• Pulmonary compromise o Disadvantage: can increase friction between
• Intrapartum infection blade and vaginal wall
• Neurological conditions o Used for: fetus with a molded head or for
rotation
• Exhaustion and prolonged 2nd stage
• Pseudofenestration: forceps blade is smooth on the outer
CLASSIFICATION AND PREREQUISITES maternal side but indented on the inner fetal surface
o Goal: reduce head slipping yet improve ease and
• 2 most important discriminators of risk for both mother
safety application and removal of forceps
and neonate are: STATION and ROTATION
compared with pure fenestrated blades
Procedure Criteria
OCCIPUT POSTERIOR POSITIONS
Outlet forceps Scalp is visible at introitus without separating
the labia • If ROP → rotation is clockwise to bring it to an ROA or OA
Fetal skull has reached pelvic floor position
Fetal head is at or on perineum • LOP position → rotation is counterclockwise
Head is OA or OP or right or left OA or OP but • For forceps rotations from an OP to OA position, Kielland
rotation <45 degrees instruments are preferred because they have a less
Low forceps (2 Leading point of fetal skull is at station >+2cm pronounced pelvic curve
types) and not on pelvic floor and rotation is <45
degrees or rotation is >45 degrees OCCIPUT TRANSVERSE POSITIONS
Midforceps Station between 0 and +2 • Rotation is required for delivery
PREREQUISITES • Kielland forceps
• Engaged head • Simpson forceps
• Vertex
• Known fetal head position VACUUM EXTRACTION
• CPD not suspected • Proper cup placement over the flexion point
• Fetal weight estimated • Flexion point: found along the sagittal suture
• Experienced operator approximately 3cm in front of the posterior fontanel and
• Ruptured membranes approximately 6cm from the anterior fontanel
• Completely dilated cervix
• Adequate anesthesia CHAPTER 30
• Emptied maternal bladder → to provide additional pelvic
space and minimize bladder trauma
• No fetal coagulopathy Cesarean Delivery and Peripartum Hysterectomy
• No fetal demineralization disorders
77
 • CS hysterectomy: when performed at the time of CS
• Postpartum hysterectomy: if done within a short time
after vaginal delivery
• Peripartum hysterectomy: combination of the 2
• Adnexa are not usually removed
• Radical hysterectomy removes the uterus, parametrium
and proximal vagina to achieve tumor excision with
negative margins
ACOG
ACOG does not encourage the practice of swabbing the newborn’s
mouth with a gauze that was incubated in the maternal vagina 1
hour prior to surgery due to few data and potential for transmission
of harmful organisms.
CAVEAT REMARKS
Timing • There must be an assurance of fetal maturity
before scheduled elective surgery
Preoperative • No benefits gained from presurgical enema
care • Solid food avoided 6-8 hours prior to the
procedure
• Scarce data on ERAS
• Antacid is given to minimize lung injury risk from
gastric acid aspiration
• Hair removal at the surgical site does not lower
SSI unless hair is obscuring
• Risk of VTE is increased and almost doubled in
those undergoing CS
• ACOG recommends pneumatic compression
before CS and discontinued once the woman
ambulates
Infection • CS is a clean contaminated case
prevention • Single dose of antibiotic given at the time of CS
decreases infectious morbidity
• Beta lactam antibiotic or cephalosporin or
extended spectrum penicillin
• 1g dose of cefazolin
• Additional doses needed if blood loss >1500ml or
duration of >3 hours
• CS lasting 1.5 hrs → 2g dose
• If with previous MRSA → add vancomycin
• If with significant penicillin or cephalosporin
allergy → 600mg IV clinda + aminoglycoside
• If obese → 900mg clinda
• Administer before surgical incision lowers
postoperative infection versus administration
after cord clamping
• Ideally administered 1 hr prior to CS
• Chlorhex wash
• Antibiotic prophylaxis against infective
endocarditis is not recommended (except for
those with cyanotic heart disease, prosthetic
valves or both)
CESAREAN DELIVERY TECHNIQUE
LAPAROTOMY:
• Transverse abdominal entry through Pfannenstiel or
Maylard
• Pfannenstiel:
o Transverse follow Langer lines of skin tension →
superior cosmesis and lower incisional hernia
rates
o Discouraged for cases in which a large operating
space is essential or in which access to the upper
abdomen may be needed
o Neurovascular structures (ilioinguinal and
iliohypogastric nerves and superficial and inferior
epigastric vessels) are often encountered
o 3cm above superior border of symphysis pubis
→ extended laterally 12-15cm
o Anterior abdominal fascia composed of 2 visible
layers – aponeurosis from external oblique
muscle and a fused layer of aponeuroses of
internal oblique and transverse abdominis
o Inferior epigastric vessels lie outside the lateral
border of the rectus abdominis and beneath the
fused aponeuroses of the internal oblique and
transverse abdominis muscles
• Best incision for morbidly obese is unclear
• Maylard incision:
o Differs from Pfannenstiel in that the bellies of
the rectus abdominis are transected horizontally
to widen the operator space
o More difficult due to its required muscle cutting
and isolation and ligation of inferior epigastric
arteries
• Midline Vertical:
o Begins 2-3 cm above the superior margin of the
symphysis
o 12-15cm
HYSTEROTOMY
LOW TRANSVERSE CESAREAN INCISION:
• Easier to repair
• Causes less incision-site bleeding
• Promotes less bowel or Omentum adherence to the
myometrial incision
• Before cutting → palpate fundus to identify degree of
uterine rotation
• Create a bladder flap to move bladder away from planned
hysterotomy site
• Blunt stretching of hysterotomy site is associated with
fewer unintended incision extensions, shorter operative
time and less blood loss
• Delivery of the Fetus with Impacted Head on the Pelvis:
o Push method (assistant pushes head)
o Pull method: delivery through breech
o Fetal pillow: distensible intravaginal balloon
inflated to elevate the fetal head
• Prevention of PPH:
o Carbetocin: longer acting oxytocin derivative
that provides suitable hemorrhage prophylaxis
o Carboprost: 15-methyl derivative of
prostaglandin F2a
o Tranexamic acid added to standard oxy infusion
to decrease blood loss
▪ Antifibrinolytic action
• Uterine repair:
78
 o IUD insertion is completed prior to hysterotomy
closure
o Single layer closure faster and not associated
with higher rates of infection or transfusion
o Number of layers do not significantly affect
complication rates in the next pregnancy
o Omission of closure of 3rd layer causes no
postoperative complications
o Handle tissues delicately, minimize tissue
ischemia to avoid adhesions
• Abdominal closure:
o Fascia is closed by a continuous nonlocking
technique with a delayed absorbable suture
o If with high risk of infection → monofilament
suture
o Subcutaneous need not be closed if <2cm
o If thick layers → suture to minimize seroma and
hematoma formation
o Skin: subcuticular 4-0 delayed absorbable
o Skin suturing longer but staples have higher
wound separation
JOEL-COHEN AND MISGAV LADACH TECHNIQUES
• Joel Cohen creates a straight 10cm transvers skin incision
3cm below the ASIS
• Misgav Ladach: peritoneum is entered bluntly
CLASSICAL CESAREAN INCISION
• Prone to rupture with subsequent pregnancies
• Indicated when:
o Densely adherent bladder from previous surgery
o Myoma occupies LUS
o Cervical ca
o Massive maternal obesity precludes safe access
to LUS
o Previa with anterior placentation
o Transverse lie back down
• Uterine Incision:
o Begin as low as possible and in the LUS
• Uterine Closure:
o Layer of 0 or 1 chromic catgut with running stitch
to approximate the deeper length of incision
o Outer layer is closed with running suture while
assistant brings incision closer
PERIPARTUM HYSTERECTOMY
• Most commonly performed to arrest or prevent
hemorrhage from intractable uterine atony or abdominal
placentation
• Complications: greater blood loss and risk of urinary tract
damage
Supracervical Hysterectomy:
• Uterine body is amputated immediately above the level of
uterine artery ligation
• Cervical stump closed with continuous or interrupted
chromic catgut suture
• Preferred for women who would benefit from a shorter
surgery or those with extensive adhesions that threaten
urinary tract injury
Urinary Bladder Injury
• Cystotomy: bladder laceration most commonly occurring
during blunt or sharp dissection in the vesicouterine space
to create the bladder flap
• Dome is lacerated in 95% of cases
• Injuries at trigone 5%
• Bladder may be closed with a 2 or 3 layer running closure
using 3-0 suture
• Postoperative care: IFC for 7-14 days to permit healing and
minimize risk of fistula
Ureteral Injury:
• IFC remains for 7-10 days and ureteral catheters are
removed via cystoscopy after 14 days
• IVP not necessary
Bowel Injury:
• May cause peritonitis
POST OPERATIVE CARE
EUVOLEMIA EVALUATION
• Average sized woman with Hct 0.30 or more with normally
expanded blood and ECF will tolerate blood loss up to 2L
without difficulty
• 1500ml – average blood loss in elective CS
HOSPITAL CARE UNTIL DISCHARGE
• Assess in her room at least hourly for 4 hours then Q4
• Deep breathing and coughing encouraged to prevent
atelectasis
• Maintenance of IVF proves adequate after surgery until
consistent oral intake is reestablished
• Bladder and Bowel Function:
o IFC can be removed 12 hrs postoperatively or the
morning after
o Prevalence of urinary retention 3-7%
o Liquids or solid food may be offered within hours
of surgery and advanced as tolerated
• Ambulation and Wound Care:
o Early ambulation lowers thromboembolism risk
o Surgical dressing removed after 24 hours to
inspect incision daily
o Day 3 postpartum – may take a bath
o Staples often removed on the 4th day then steri
strips for 1 week to reinforce skin edge integrity
HOSPITAL DISCHARGE
• Average hospitalization length: 3-4 days
• Activities during the 1st week: selfcare and newborn care
with assistance
• Driving resumed when pain does not limit the ability to
brake quickly and when narcotic meds are not in use
• Intercourse resumed in 44% by 6 weeks, 81% by 3 months
and 97% at 1 year
• Return to work as early as 6 weeks
CHAPTER 31
Prior Cesarean Delivery
79
FACTORS THAT INFLUENCE A SUCCESSFULT RIAL OF LABOR IN A • Lower segment: 2-6%
WOMAN WITH PRIOR CESAREAN DELIVERY • Upper uterus: 9-32%
Low Risk • Transverse incision Imaging of prior High risk: <2.0mm
• Prior vaginal delivery incision: *strong Intermediate risk: 2.0-2.4mm
• Appropriate counselling predictor (34-39 Low risk: >2.5mm
• Sufficient personnel and equipment wks.)
Favors success • Teaching hospital Prior uterine rupture Greatest recurrence
• White race Prior vaginal delivery Improves prognosis
• Spontaneous labor Interdelivery interval Complete uterine involution is at least 6
• Prior fetal malpresentation months
• 1 or 2 prior transverse incisions <18 months: 3fold greater risk for rupture
• Nonrecurrent indication
Prior CS indication Breech – highest VBAC rate 90%
• Current preterm pregnancy
Fetal compromise – 80%
Increased failure • Single mother Labor arrest – 60%
rate • AMA
Fetal size Increasing fetal size not favorable
• Macrosomic fetus
Fetal weight <4000g: 1%
• Obesity
>4000g: 1.6%
• Breech
>4250g: 2.4%
• Multifetal pregnancy
Multifetal gestation Safe to undergo
• Preeclampsia
• AOG >40 weeks
Maternal obesity Normal BMI: 85%
• Low vertical / unknown incision BMI 25-30: 78%
• Medical disease BMI 30-40: 70%
• Multiple prior CS deliveries BMI >40: 61%
• Education <12 years
• Short interdelivery interval
• Liability concerns
High Risk • Classical or T incision
• Prior rupture
• Patient refusal
• Transfundal surgery LABOR AND DELIVERY CONSIDERATIONS
• Obstetrical contraindications (previa)
• Inadequate facilities Timing • 39 weeks better
• Aging should be sure
DELIVERY ROUTE RISKS Cervical Ripening • Induction only by amniotomy
MATERNAL RISKS: and Labor • Oxytocin implicated to increase rates of
• Uterine Rupture Classifications: Stimulation uterine rupture
o Complete: all layers of the uterine wall separated • Prostaglandins not advised
o Incomplete: uterine muscle is separated but Epidural analgesia • May safely be used
visceral peritoneum is intact Uterine scar • Benefits are unclear
▪ AKA uterine dehiscence exploration
• Risk of maternal death is reduced for women undergoing
TOLAC compared with Elective RCS UTERINE SCAR RUPTURE
DIAGNOSIS:
FETAL AND NEONATAL RISKS • Most common sign: Nonreassuring fetal heartrate
• TOLAC associated with a higher risk of HIE patterns with variable decelerations that may evolve into
late decelerations and bradycardia
CANDIDATES FOR TRIAL OF LABOR
• ACOG: most women with one previous LTCS are DECISION TO DELIVERY TIME:
candidates and should be counseled regarding TOLAC • Mortality rates range from 50-75%
Factor Remarks • Fetal condition depends on the degree to which placental
Prior Uterine Incision MOST IMPORTANT FACTOR implantation remains intact
Classical: 2-9%
• May rupture before labor onset
and several weeks before term CHAPTER 32
T shaped: 4-9%
Low vertical: 1-7% The Newborn
• ACOG: may undergo TOLAC
TRANSITION TO AIR BREATHING
One low transverse: 0.2-0.9%
• Newborn must promptly convert from placental to
Multiple low transverse 0.9-1.8%
pulmonary gas exchange
Prior preterm cesarean delivery: increased
Prior uterine rupture: •
LUNG FLUID CLEARANCE MECHANISMS
80
 • Large release of fetal adrenaline late in labor stimulates • To assess the effectiveness of resuscitative measures
pulmonary epithelial cells to stop secreting and instead • 5 minute score predicts survival during the first 28 days of
start reabsorbing lung liquid as a result of sodium-channel life
activation • Certain elements of the Apgar score are partially
• Mechanical forces aid lung fluid clearance during labor → dependent on the physiological maturity of the newborn
compression of fetal thorax and abdomen as they pass and a healthy, preterm neonate may receive a low score
through the birth canal → lung liquid expulsion only because of immaturity
• Significant amount of lung liquid is cleared after birth • Inappropriate to use an Apgar score alone to diagnose
o Lung interstitial tissue pressure rises to a point asphyxia
that fluid can actually move back into the Fetal Acid-Base Physiology
airspaces during expiration • One principal cause of fetal acidemia: drop in
• Surfactant (synthesized by Type II pneumocytes) lowers uteroplacental perfusion
alveolar surface tension and helps maintain lung inflation o Creates CO2 retention → acidemia and if it is
by preventing alveolar collapse severe enough → mixed or metabolic acidemia
• Fetal oxygenation and pH generally decline during course
CARE IN THE DELIVERY ROOM of normal labor
Umbilical Cord Clamping • Lower limits of normal pH in the NB: 7.04-7.10
• Only reported negative outcome is hyperbilirubinemia • Respiratory Acidemia: acute interruption in placental gas
leading to a higher rate of phototherapy exchange accompanied by subsequent CO2 retention and
• ACOG: 30-60 seconds delay is best respiratory acidemia
o Most common antecedent factor: transient
umbilical cord compression
o Not harmful to the fetus
• Metabolic Acidemia: fetus begins to develop MA when O2
deprivation is sufficiently long and severe to require
anaerobic metabolism for cellular energy needs
o ACOG: umbilical arterial pH <7.0 and a base
deficit of >12
o High risk for: Hypoxic ischemic encephalopathy
Newborn Resuscitation
• When deprived of adequate gas exchange, either before or PREVENTIVE CARE
after birth, neonates demonstrate a well-defined sequence
of events leading to apnea Eye Infection Prophylaxis • Ophthalmia neonatorum –
Primary With oxygen deprivation and CO2 elevation → mucopurulent conjunctivitis
Apnea transient period of rapid breathing → breathing commonly due to gonococcal or
stops chlamydial infections
Accompanied by a fall in HR, loss of NM tone • Common cause: N. gonorrhea
Simple stimulation reverses this • Mx: 1% silver nitrate or 0.5%
Secondary If oxygen deprivation and asphyxia persist → NB erythromycin
Apnea will develop deep gasping respirations • Neonate born to a mother with
Further decline in HR, fall in BP, loss of NM tone untreated gonorrhea → ceftriaxone
Will not respond to stimulation 100mg/kg IM or IV
Will not spontaneously resume respiratory efforts • Conjunctivitis in a NB up to 3yo
should prompt consideration for
Resuscitation Protocol chlamydial infection →
• Maintain euthermia (36.5-37.5) azithromycin for 5 days or oral
• Put plastic ponchos to slow evaporative heat losses erythromycin for 14 days
• Routine intubation and suctioning of meconium stained AF Vitamin K • To prevent vitamin K dependent
is no longer recommended for the nonvigorous newborn hemorrhagic disease of the NB
• Chest compressions: • Single IM dose of vitamin K 0.5-1mg
o Compressions are delivered on the lower third of within 1 hour of birth
the sternum at a depth sufficient to generate a NBS • 29 NB conditions detected
palpable pulse
• Epinephrine: recommended IV dose is 0.01-0.03mg/kg ROUTINE NEWBORN CARE
• Discontinuation of resuscitation:
o Reasonable to discontinue resuscitative efforts Care of skin and umbilical • Keeping cord dry is sufficient care
for a neonate who remains without a heartbeat cord • 24 hours → cord stump loses its
despite at least 10 minutes of continuous and
characteristic bluish white
adequate resuscitative efforts
appearance → separation within
the first 2 weeks (3-45 days range)
EVALUATION OF NEWBORN CONDITION
• If with infection → most likely due
APGAR Score
81
 to S. aureus, E coli or Group B strep • Perinatal infection
Feeding and weight loss • Exclusive BF until 6 months • Preterm birth continues to be the single most important
• Most term NB thrive best when fed risk factor
8-12x a day for 15 minutes each • Other miscellaneous: fetal anemia, TTTS, intrauterine
episode transfusions, fetal alcohol syndrome
Stools and urine • First 2-3 days: meconium (consists ACOG: EFM does not reduce incidence of long term neurological
of desquamated epithelial cells impairment
from the intestinal tract, mucus,
epidermal cells and lanugo that NEONATAL ABSTINENCE SYNDROME
have been swallowed with AF) • Drug withdrawal syndrome that most commonly follows in
• Day 3 or 4: yellowish utero exposure to maternal opioids
Neonatal • 2nd-5th day of life → physiologic • Hypertonia, autonomic instability, irritability, poor sucking
hyperbilirubinemia jaundice and seizures
Male circumcision • Lowers incidence of penile cancer
and cervical ca among their HEMATOLOGICAL DISORDERS
partners
• Lowers risk of HIV Anemia • After 35 weeks, mean cord hgb
approximates 17g/dl (values below 14 are
considered abnormal)
• Delayed cord clamping associated with a
mean neonatal hgb rise of 1.5g/dL
Polycythemia and • Associated with chronic hypoxia in utero,
hyper viscosity TTTS, placental and fetal growth restriction,
fetal macrosomia from maternal diabetes
and transfusion at delivery
Hyperbilirubinemia • Hepatic maturation is incomplete
• Feal protection from unconjugated bilirubin
is lost after delivery
• Serum bilirubin levels usually rise for 3-4
days to reach up to 10mg/dl → levels fall
rapidly thereafter
CHAPTER 33 • Acute bilirubin encephalopathy: first days
of life → hypotonia, poor feeding, lethargy
and abnormal auditory evoked responses
Diseases and Injuries of the Term NB • Kernicterus: chronic form → neurotoxicity
RESPIRATORY DISTRESS SYNDROME after bili deposition and staining of the
• Caused by lung immaturity and insufficient surfactant basal ganglia and hippocampus
• Most frequent causes: perinatal infection with sepsis • Prevention: phototherapy
syndrome in 50% Hemorrhagic • Spontaneous internal or external bleeding
• Elective CS: 27% disease of the NB beginning any time after birth
• Severe asphyxia: 10% • Apparent 2-5 days after birth in neonates
• Meconium aspiration: 7% not given vitamin K prophylaxis
• Treatment: mech vent and replacement of surfactant Thrombocytopenia • Extension of fetal disorder such as infection
• Antenatal maternal corticosteroid will enhance surfactant with B19 parvovirus, CMV, or TORCH
synthesis in late preterm fetuses (34-37 weeks) • Immune thrombocytopenia: in women with
SLE or autoimmune disease wherein
NEONATAL ENCEPHALOPATHY maternal antiplatelet IgG is transferred to
• Mild: hyper alertness, irritability, jitteriness and fetus
hypertonia and hypotonia • Alloimmune thrombocytopenia: maternal-
• Moderate: lethargy, severe hypertonia and occasional fetal platelet antigen disparity →
seizures transplacental antiplatelet IgG antibodies
• Severe: coma, multiple seizures and recurrent apnea cause severe fetal thrombocytopenia and
• Sentinel events: ruptured uterus, severe placental bleeding
abruption, cord prolapse and AF embolism
INJURIES OF THE NEWBORN
CEREBRAL PALSY Cranial Injuries:
Risk Factors: • External: skull or mandibular fracture
• Evidence of genetic abnormalities (maternal MR or fetal • Intracranial
congenital malformation) • Covert
• BW: <2000g
• Birth before 32 weeks Intracranial Hemorrhage Extracranial Hematomas

82
 • From hypoxia and • Cephalhematoma or
ischemia subgaleal hemorrhage
• Asymptomatic in • Traversing across the
many cases subgaleal space are
• Lowered by large, valveless
elimination of difficult emissary veins which
instrumented vaginal connect the dural
deliveries sinuses inside the skull
• Prognosis depends on with superficial scalp
its location and extent veins
• Cephalhematoma:
cranial subperiosteal
hematomas → may not
be apparent until hours
after delivery when
bleeding sufficient to
raise periosteum has
occurred
• Caput succedaneum:
swelling of the scalp
from soft tissue edema
that overlies the
periosteum → subsides
within hours or days
• Subgaleal hemorrhage:
laceration of one of the
emissary veins with
bleeding between the
galea aponeurotica and
skull periosteum
Skull Fractures:
• Linear and depressed fractures and occipital osteodiastasis
• More common when head is tightly wedged in the pelvis
• May result from skull compression against the sacral
promontory, by hand pressure used to life the head during
CS or from transvaginally applied upward hand pressure by
an assistant
Peripheral Nerve Injuries
Brachial Plexopathy • Breech delivery and shoulder dystocia
are risks for this trauma
• Injury damages the nerve roots that
supply the brachial plexus – C5-8 and
T1
• C5-6: Erb or Duchenne paralysis
• C8-T1: Klumpke paralysis – hand is
flaccid
• Horner syndrome: total involvement of
all brachial plexus
Facial paralysis • Trauma to facial nerve as it emerges
from the stylomastoid foramen
• More common with low forceps
Fractures
• Clavicular fractures protect against brachial plexopathy
when there is shoulder dystocia
• Humeral fractures: infrequent
• Femoral fractures: associated with vaginal breech
• Mandibular fractures: breech or Zavanelli
Soft Tissue Injuries
• Subcapsular hepatic hematomas that present as inguinal
and scrotal hematoma
• Stabler sign: ecchymoses of the inguinal region
• Bryant sign: ecchymoses of the scrotum
CHAPTER 34
The Preterm NB
Respiratory Distress Syndrome
• AKA hyaline membrane disease
• Tachypnea develops, chest wall retracts, and expiration is
accompanied by nostril flaring and grunting
• CXR: air bronchogram sign
• Treatment: CPAP to prevent collapse of unstable alveoli
• Mech Vent → prone to bronchopulmonary dysplasia
(BPD) AKA barotrauma and volutrauma
• Caffeine: bronchodilatory effects
• Vitamin A: if low vit A = greater risk of developing BPD
• Surfactant Prophylaxis and Rescue
o Contain biological or animal surfactants such as
bovine – Survanta, calf – Infrasurf or porcine –
Curosurf
• Prevention:
o Antenatal corticosteroids
▪ ACOG: give steroids to all at risk for
preterm birth
• At 32-34 weeks, concentration of lecithin relative to
sphingomyelin begin to rise
Necrotizing Enterocolitis
• Abdominal distention, emesis, ileus, bilous gastric
aspirates, bloody stools
• Primarily in low birthweight newborns
• Treatment: abdominal decompression, bowel rest, broad
spectrum antibiotics, parenteral nutrition
Retinopathy of Prematurity
• Normally fetal retina vascularizes centrifugally from the
optic nerve starting at approximately the fourth month
and continues until shortly after birth
Brain Disorders
Intracranial • Primary subarachnoid hemorrhage: more
Hemorrhage common in preterm and frequently
benign
• Cerebellar hemorrhage: cause of serious
sequelae
• IVH: preterm, relatively common
• Subdural hemorrhage: more frequent in
term and can be serious
• Miscellaneous: term, variable concern
Periventricular- • If fragile capillaries in the germinal matrix
Intraventricular rupture → blood escapes into
Hemorrhage surrounding tissues and may extend into
the ventricular system and brain
parenchyma
• Common in preterm neonates esp those
before 32 weeks
83
 • Most hemorrhages develop within 72
hours and as late as 24 days REPRODUCTIVE TRACT INVOLUTION
• Grade 1: hemorrhage limited to germinal
matrix Repro Organ Changes
• Grade 2: intraventricular hemorrhage Birth canal • Begins soon after delivery
• Grade 3: hemorrhage with ventricular • Rugae begin to reappear by the 3rd week but
dilation less prominent than before
• Grade 4: parenchymal extension of • Hymen scar to form the myrtiform caruncles
hemorrhage • Vaginal epithelium in the hypoestrogenic
state begins to proliferate 4-6 weeks
CHAPTER 35
Stillbirth
Death prior to complete expulsion or extraction from the mother of
a product of conception irrespective of the duration of pregnancy
and which is not an induced termination of pregnancy. Death is
indicated that the fetus does not breathe or show any other
evidence of life.

Cause Percentage Examples

Obstetrical 29 Abruptio, multifetal, ROM 20-24
weeks
Placental 24 Uteroplacental insufficiency,
maternal vascular disorders
Fetal malformations 14
Infection 13
Umbilical cord 10 Prolapse, stricture, thrombosis
abnormalities
Hypertensive disorders 9 Pre-ec, CHVD
Medical complications 8 DM, APAS
Undetermined 24
Risk Factors:
• Advanced maternal age Uterus • After delivery → fundus lies slightly below umbilicus
• African-American • Immediately postpartum → anterior and posterior
• Smoking walls are 4-5cm thick
• Illicit drug use • Myometrial involution is a series of destruction or
• Maternal medical diseases deconstruction beginning as soon as 2 days after
delivery
• ART
• Size decreases markedly
• Nulliparity
• 1 week postpartum: 500g
• Obesity
• 2 weeks postpartum: 300g
• Prior adverse pregnancy outcome (prior preterm birth or
growth restricted fetus) • 4 weeks postpartum: involution is complete, 100g
• Prior stillbirth: 5fold higher • Sonographically: uterus and endometrium return to
pregravid size by 8 weeks
Evaluation of the Stillborn Fetus • Within 2-3 days after delivery: remaining decidua
• 35% have major structural anomalies becomes differentiated into 2 layers:
o Superficial layer: becomes necrotic and sloughed
• 20% have dysmorphic features
off
• 8% chromosomal abnormalities
o Basal layer: adjacent to myometrium remains
intact → source of new endometrium
Prior Stillbirth
• 16th day onward: fully restored endometrium
• Antepartum surveillance should begin at 32 weeks or later
• Primiparas: uterus remains tonically contracted
in the otherwise healthy woman with a history of stillbirth
following delivery
• Multiparas: contracts vigorously at intervals →
CHAPTER 36 “afterpains” which decrease in intensity and become
mild by day 3
• Lochia: erythrocytes, shredded decidua, epithelial
The Puerperium cells and bacteria
• Time following delivery during which pregnancy induced o Lochia Rubra: blood “red”
maternal anatomical and physiological changes return to o Lochia Serosa: after 3-4 days, pale
the nonpregnant state o Lochia Alba: after 10th day, admixture of
• 4-6 weeks leukocytes and reduced fluid content, white or
84
 yellow-white color
o Range: 24-36 days
Placental • Complete extrusion takes up to 6 weeks
Site • Immediately after delivery: palm sized
Involution • End of 2nd week: 3-4cm in diameter
• Exfoliation process prompted by undermining of the
implantation site by new endometrial proliferation
• Extension and “downgrowth of endometrium from
the margins of the placental site + development of
endometrial tissues from glands and stroma in the
decidua basalis
• Subinvolution: may be hindered due to infection,
retained placental fragments or other causes
o Varied intervals of prolonged lochia
o Irregular and excessive uterine bleeding
o Methylergonovine 0.2mg oral every 34 hours for
24-48 hours
o MCC: 1. Chlamydia trachomatis, 2. Incompletely
remodeled uteroplacental arteries
o Mild infection: azithromycin or doxycycline
• Late Postpartum Hemorrhage:
o Secondary postpartum hemorrhage: bleeding 24
hours to 12 weeks after delivery
o Result of abnormal involution of the placental
site
o Occasionally caused by retention of a placental
fragment or by a uterine artery pseudoaneurysm
→ placental polyp
o May also be caused by von Willebrand disease
Urinary Tract • GFR returns to prepregnancy baseline by 2
weeks
• Dilated ureters and renal pelves return to
their prepregnant state by 2-8 weeks
postpartum
o May cause symptomatic UTI (due to
dilated collecting system + residual urine
+ bacteriuria in a traumatized bladder)
• Bladder has increased capacity and a relative
insensitivity to intravesical pressure →
overdistention / incomplete emptying and
excessive residual urine are frequent
• Retention more common with narcotic
analgesia use
Peritoneum and • Several weeks to return to normal
Abdominal wall • Aided by exercise
• Exercise may be started any time after NSD
and 6 weeks after CS to allow fascia to heal
and abdominal soreness is tolerable
• Striae gravidarum: silvery abdominal striae
Blood and Blood • Hematological and Coagulation Changes:
Volume o Marked leukocytosis and thrombocytosis
(as high as 30,000/uL)
o First few postpartum days: Hgb and Hct
fluctuate
• Pregnancy Induced Hypervolemia
o If less has been lost at delivery → BV
returns to its nonpregnant level by 1
week
o CO remains elevated for 24-48 hrs
postpartum and declines to nonpregnant
values by 10 days
o SVR remains in the lower range for 2 days
PP then begins to steadily increase to
normal
• Postpartum Diuresis
o Normal pregnancy: increase in
extracellular sodium and water retention
o Decrease in sodium space of 2L during 1st
week postpartum
o Results in rapid weight loss of 2-3kg
maximal by end of 2nd PP week
o Pre-pregnancy weight returns 6 months
after delivery
LACTATION AND BREASTFEEDING
BREAST ANATOMY AND SECRETORY PRODUCTS:
• Each mature mammary gland or breast: 15-25 lobes
• Lactiferous ducts open separately on the nipple
• After delivery, breasts begin to secrete colostrum (usually
on day 2 PP)
• Colostrum:
o More protein
o Less sugar and fat
o Secretion persists for 5 days-2 weeks with
gradual transition to mature milk by 4-6 weeks
o IgA offers protection against enteric pathogens
o Has: complement, macrophages, lymphocytes,
lactoferrin, lactoperoxidase and lysozymes
• Mature milk:
o Fat, proteins, carbohydrates, bioactive factors,
minerals, vitamins, hormones
• Nursing mother can easily produce 600ml of milk daily
• Milk lacks vitamin K, vitamin D is low (22IU/mL only)
• Whey-to-casein ratio: 60:40 → ideal for absorption
• Prolactin: actively secreted into breast milk
ENDOCRINOLOGY OF LACTATION
• With delivery → maternal serum levels of progesterone
and estrogen decline → removes inhibitory influence of
progesterone on alpha lactalbumin production →
stimulates lactose synthase to increase milk lactose
• Progesterone withdrawal → prolactin acts unopposed in
its stimulation of alpha-lactalbumin
• Activation of calcium sensing receptors (CaSR) in
mammary epithelial cells downregulates parathyroid
hormone related protein (PTHrP) → increased calcium
transport into milk
• Serotonin also maintains milk production
• Prolactin: essential for lactation
• Sheehan syndrome: they do not lactate  due to decrease
prolactin
• Stimulus from the breast → release of dopamine
“prolactin-inhibiting factor” from the hypothalamus →
increased prolactin secretion
• Oxytocin Release:
o Posterior pituitary secretes oxytocin in a
pulsatile fashion → stimulates milk expression
from a lactating breast by causing contraction of
myoepithelial cells in the alveoli and milk ducts
o Let down reflex
85
IMMUNOLOGICAL CONSEQUENCES OF BREASTFEEDING
• Antibodies in human milk are specifically directed against
maternal environmental antigens such as E. coli
• Decreases incidence of ear, respiratory, GI infections,
necrotizing enterocolitis and SIDS
• Milk also contains T and B lymphocytes

NURSING
• Provides age specific nutrients, immunological factors and
antibacterial substances
• Associated with decreased postpartum weight retention

ADVANTAGES OF BREASTFEEDING: (PEEDO NIDS milk)

Psychological
Economical
Environmental
Decreases risk for acute and chronic diseases
Optimal growth and development

Nutritional
Immunological
Developmental
Social

86
10 STEPS TO SUCCESSFUL BREASTFEEDING
CARE OF BREASTS
• Nipple pain usually subsides by 10 days
• If fissuring is severe → NB should not be permitted to
nurse on the affected site, but breast is to be emptied
regularly with a pump until lesions are healed
CONTRAINDICATIONS TO BREASTFEEDING
• Street drugs or uncontrolled alcohol use
• Infant with galactosemia
• HIV active
• Active, untreated tuberculosis
• Taking certain medications
• Undergoing breast cancer treatment
• Women with active herpes simplex on breast
DRUGS SECRETED IN MILK
• Cytotoxic drugs interfere with cellular metabolism and
potentially cause immune suppression or neutropenia,
affect growth and at least theoretically increase risk of
childhood cancer
o Cyclophosphamide
o Cyclosporine
o Doxorubicin
o Methotrexate
o Mycophenolate
• Drugs
o Marijuana and alcohol
• Radioactive isotopes:
o Copper, gallium, indium, iodine, sodium and
technetium
o Goal: radionuclide with the shortest excretion
time in breast milk
o After the study: pump breasts to maintain milk
but discard all milk produced (15 hours to 2
weeks depending on the isotope used)
BREAST ENGORGEMENT
• Milk leakage and breast pain (peak days 3-5) after delivery
• Cool packs and oral analgesics for 12-24 hours aid
discomfort
• Fever seldom persists for longer than 4-16 hours
OTHER ISSUES WITH LACTATION
• Inverted nipples: lactiferous ducts open directly into a
depression at the center of the areola
• Extra breasts – polymastia
• Extra nipples – polythelia
• Galactocele: milk duct that becomes obstructed by
inspissated secretions
o May cause pressure symptoms and have the
appearance of an abscess
o May resolve spontaneously or require aspiration
• Agalactia – complete lack of mammary secretion
• Polygalactia – mammary secretion is excessive
HOSPITAL CARE
• Likelihood of hemorrhage is greatest immediately
postpartum even in normal births
• Uterus is closely monitored at least 1 hour after delivery
• No dietary restrictions for NSD → may eat 2 hrs after
• Oral iron supplementation for at least 3 months after
delivery and hematocrit evaluation at the first postpartum
visit
Perineal Care
• Severe perineal, vaginal or rectal pain always warrants
careful inspection and palpation
• Beginning 24 hrs PP → warm sitz bath
• Episiotomy is healed and nearly asymptomatic by week 3
Bladder Function
• Risk factors for increased likelihood of retention:
o Primiparity
o CS
o Perineal laceration
o Oxytocin induced or augmented labor
o Operative vaginal delivery
o Catheterization during labor
o Labor duration > 10 hours
• When catheter is removed and cannot void after 4 hours
→ straight catheterization → if >200ml bladder is not
functioning appropriately and catheter is left for another
24 hours
Pain, Mood and Cognition
• Postpartum blues – emotional letdown that follows the
excitement and fears experienced during pregnancy and
delivery, discomforts of the early puerperium, fatigue from
sleep deprivation, anxiety over the ability to provide
appropriate newborn care and body image concerns
o Mild and self-limited to 2-3 days up to 10 days
Neuromusculoskeletal Problems
• Obstetrical Neuropathies:
o Lateral femoral cutaneous neuropathies were
the most common
o Femoral neuropathies
o Risk factors: nulliparity, prolonged second stage
labor, pushing for a long duration in the semi-
Fowler position
o Median duration 2 months (2 wks. – 18 mos.)
87
 o CS – iliohypogastric and ilioinguinal nerve
injuries
Musculoskeletal Injuries
• Normal distance of symphyseal joint is 0.4-0.5cm and
symphyseal separation >1cm is diagnostic for diastasis
CHAPTER 37
• Treatment is conservative
• Rest in a lateral decubitus position Puerperal Complications
• Pelvic binder
• Surgery necessary if >4cm Pelvic infection continues to be the most important source of
Immunizations maternal morbidity and mortality
• D negative woman who gives birth to a D positive newborn
is given 300ug of anti-D immune globulin shortly after PUERPERAL PELVIC INFECTION
delivery • Any bacterial infection of the genital tract after delivery
Hospital Discharge • Infection + preeclampsia + obstetrical hemorrhage = Lethal
• Up to 48 hours – uncomplicated NSD triad of maternal death causes before and during the 20th
• Up to 96 hours – uncomplicated CS century
Contraception:
• Women not breastfeeding have return of menses usually Puerperal Fever • Temperature of 38 degrees or higher
within 6-8 weeks • Most persistent fevers after childbirth are
• Ovulation occurs at a mean of 7 weeks but ranges from 5- caused by infection
11 weeks • Spiking fevers of 39 or higher that develop
• Resumption of Ovulation: within the first 24 hours PP may be
o Resumption frequently marked by return of associated with virulent pelvic infection
normal menses caused by Group A strep
o BF episodes lasting 15 minutes 7x daily delayed • Other causes: breast engorgement, UTI,
ovulation perineal lacerations, episiotomy or
o Ovulation can occur without bleeding abdominal incision, respiratory
o Bleeding can be anovulatory complications after cesarean delivery
o Risk of pregnancy 4% • Approximately 15% of those who do not
• Progestin only contraceptives (progestin pills, DMPA, breastfeed develop postpartum fever from
Progestin implants) do not affect quality of milk breast engorgement
• First sign of renal infection: fever →
HOME CARE costovertebral angle tenderness, nausea,
Coitus vomiting
• 2 weeks – based on desire and comfort • Atelectasis: hypoventilation, best
• Postpartum vulvovaginal epithelium is thin and little prevented by coughing and deep breathing
lubrication due to hypoestrogenic state following delivery on a fixed schedule following surgery;
which lats until ovulation resumes thought to stem from normal flora that
Late Maternal Morbidity proliferate distal to obstructing mucus
• Fatigue: 59% plugs
• Breast problems: 36% Uterine Infection: endometritis, endomyometritis, endoparametritis
• Anemia: 25% Predisposing • Route of delivery – single most significant
• Backache: 24% Factors risk factor for the development of uterine
• Hemorrhoids: 23% infection
• Headache: 22% • Significant morbidity following
• Blues: 21% hysterotomy, single dose perioperative
• Constipation: 20% antimicrobial prophylaxis is recommended
• Suture breakdown: 16% for all women undergoing CS
• Vaginal discharge: 15% • Lower socioeconomic status
Follow-up care: • Bacterial colonization of the lower genital
• Uncomplicated vaginal delivery → can resume activities tract – group B strep, C. trachomatis, M.
(bathing, driving and household functions) hominis, U. urealyticum, G. vaginalis
• Half expected to return to full duties within 2 weeks • GA
• Postpartum visit between 4-6 weeks • CS delivery
• Multifetal gestation
• Young maternal age
• Nulliparity
• Prolonged labor induction
• Obesity
• Meconium stained AF
Microbiology • Caused by bacteria indigenous to the

88
 genital tract
• CA-MRSA more common in CS
Pathogenesis and • Placental implantation site, decidua and
Clinical Course adjacent myometrium or cervicovaginal
lacerations
• Uterine infection after CS usually from
infected surgical incision
• Fever – most important criterion for the
diagnosis of postpartum metritis
• Chills – bacteremia or endotoxemia
Treatment • Nonsevere metritis → oral or IM
antimicrobial
• Parametria phlegmon – area of intense
cellulitis, an abdominal incisional or pelvic
abscess or infected hematoma and septic
pelvic thrombophlebitis
• Beta lactam antimicrobials are safe except
for allergic reactions
o Beta lactamase inhibitors – clavulanic
acid, sulbactam, tazobactam have been
combined with ampicillin, amox,
ticarcillin and piperacillin to extend their
spectrum
• Metronidazole – for C. difificile colitis
• Vancomycin – for gram + bacteria
Perioperative • Single dose with a 2-g dose of ampicillin or
Prophylaxis a first generation cephalosporin
• Obese women → 3g cefazolin to reach
optimal tissue concentrations
• Azithromycin to further reduce metritis
rates
• Allowing placenta to separate
spontaneously compared with removing it
manually lowers infection risk
• Exteriorizing the uterus to close the
hysterotomy may decrease febrile
morbidity
• Skin closure with staples vs suture has
higher incidence of noninfectious skin
separation
COMPLICATIONS OF UTERINE AND PELVIC INFECTIONS
• >90% → metritis responds to antimicrobial treatment
within 48-72 hours
ABDOMINAL INCISIONAL INFECTIONS
• Risk factors:
o Obesity
o Diabetes
o Corticosteroid therapy
o Immunosuppression
o Anemia
o Hypertension
o Inadequate hemostasis with hematoma
formation
• Incisional abscesses that develop following CS usually
cause persistent fever that begins on about the 4th day
• Treatment: surgical drainage and debridement of
devitalized tissue
• 4-6 days: healthy granulation is typically present
• Vacuum Assisted Wound Closure: option
• Wound dehiscence: obesity is a risk factor!
o Most manifest on the 5th post op day
o Serosanguinous discharge
NECROTIZING FASCIITIS
• High mortality rates
• Risk factors: diabetes, obesity, hypertension
• Infection is polymicrobial
• Sometimes caused by a single virulent bacterial species
such as group A beta hemolytic streptococcus
• Myofasciitis – muscle involvement
• Most of necrotizing infections do not cause symptoms
until 3-5 days after delivery
ADNEXAL ABSCESSES AND PERITONITIS
• Ovarian abscess – rarely develops in the puerperium
• Abscess is usually unilateral and present 1-2 weeks after
delivery
• Rupture is common, peritonitis is severe
• First symptoms – adynamic ileus
PARAMETRIAL PHLEGMON
• Within the leaves of the broad ligament – parametrial
cellulitis
• Considered when fever persists >72 hours despite IV
antibiotics
• Usually unilateral
• Frequently limited to the parametrium
• Most common form of extension is laterally along the
broad ligament with a tendency to extend to the pelvic
sidewall
• Clinical improvement follows continued treatment with a
broad-spectrum antimicrobial regimen
• Fever resolves in 5-7 days
• Psoas abscess – rare
SEPTIC PELVIC THROMBOPHLEBITIS
• Symptomatic improvement with antimicrobial treatment
PERINEAL INFECTIONS
• Episiotomy dehiscence is most commonly associated with
infection
• Pain 65%
• Purulent discharge 65%
• Fever 44%
TOXIC SHOCK SYNDROME
• Case fatality rate: 10-15%
• Fever, headache, mental confusion, diffuse macular
erythematous rash, subcutaneous edema, nausea,
vomiting, watery diarrhea and marked hemoconcentration
• Renal failure by hepatic failure, DIC, circulatory collapse
may follow
• Staphylococcal exotoxin – Toxic shock syndrome toxic 1
(TSST-1)
BREAST INFECTIONS
• Risk factors: difficulties in nursing, cracked nipples and oral
antibiotic therapy
• Staph aureus esp MRSA – most commonly isolated
organism
89
 • Others: coagulase negative staph and viridans streptococci Basal body temp 99 80
• Immediate source of organisms that cause mastitis → Stm 98 80
infant’s nose and throat Sdm 95 88
• Infection usually resolves within 48 hours after treatment Two day 96.5 86
• Dicloxacillin 500mg orally 4x a day for 10-14 days
• Erythromycin if penicillin sensitive Infections and Breastfeeding
• If caused by resistant, penicillinase producing staph or if
resistant organisms are suspected while awaiting culture HIV: exclusive breastfeeding for 1st 6 months of life unless (+)
→ vancomycin, clindamycin or TMX-SM replacement feeding
On ARV: significant reduction of transmission risk
BREAST ABSCESS No ARV: mixed feeding → 10-20/100 will get infected; exclusive bf
• Abscess should be suspected when defervescence does → 1/2
not following within 48-72 hours of mastitis treatment or POGS CPG: avoidance of BF → BEST CHANCE for decreased risk
when a mass is palpable
• Can be large PTB: active, untreated PTB: do not breastfeed
• Treatment: surgical drainage Anti tb x 2 weeks: noninfectious
o Sonographically guided needle aspiration using
local anesthesia: 80-90% success rate HSV, breast: active lesions on the breast: do not breastfeed
▪ Quicker healing at 8 weeks

CHAPTER 38
Contraception
Top Tier (Most Effective)
• IUD
• Levonorgestrel implants
• Female sterilization
• Male sterilization
Second Tier (Very Effective)
• Combination pill
• Vaginal ring
• Patch
• DMPA
• Progestin only pill
Third Tier (Effective)
• Condom
• Diaphragm
• Fertility awareness
Fourth Tier (Least Effective)
• Spermicides
• Sponge
• Withdrawal
• No contraception

Saliva ovulation
Start at endo f menses
98% accuracy
No food or fluid → Rinse mouth → Wait 5 mins → Collect saliva →
Center of scope → Wait 30 mins → Check light: if ferning → avoid
sex

3 requirements for LAM:

• No menstrual cycle
• Baby <6 months of age
• Full / near full breastfeeding (on demand 10-12x/d,
daytime >4 hrs interval, nighttime: not >6h interval)

Effectiveness of FAB methods:

Method Perfect Use Typical Use
Billings 97 80

90
 Method Action AE CI Others (Timing)
IUD • Failure rate: below • Lost device – expulsion common during the first month • Post pregnancy • Wait for complete
*globally: 14% 1% o Instruct to palpate strings each month after menses infection uterine involution →
*32x32mm with • Endometrial atrophy o Rate of expulsion higher in <25 yo • Active breast cancer at least 6 weeks after
52mg levonorgestrel → hinders normal o TVS can be used to ascertain if the device lies within the uterus • Breast cancer disease delivery
releasing cylinder implantation o If sonography is inconclusive → plain radiograph free > 5 years • For instrumented
reservoir • Create scant, • Perforation • Cirrhosis insertion following
viscous cervical o Most occur at time of insertion • Liver tumors vaginal delivery →
mucus → obstructs • Menstrual changes • At risk for GC/CT resterilize the vulva
sperm motility o Dysmenorrhea and bleeding irregularities • Distorted uterine and change gloves
• Inflammatory action o Copper IUD: heavy bleeding may cause iron deficiency cavity after placental
decreases egg and o LNG IUS: irregular spotting for up to 6 months after placement → progressive • GTD surveillance delivery
sperm viability amenorrhea after 2 years • For nonpregnant:
• If fertilization occurs • Infection insertion near end of
→ inflammatory o Greatest during the first months after insertion normal mens when
actions are directed o Pathogens: N. gonorrhea, C. trachomatis and vaginal flora cervix is softer
to the blastocyst o Routine antimicrobial prophylaxis not recommended (even if with heart problem) • Treat infection before
• Copper IUD – rise in o Women at low risk for STDs (adolescents) be considered good candidates insertion
cervical mucus to o Safe also for HIV and may be used by immunocompromised • Trim string to allow 3-
decrease sperm o If PID fails to improve for 48-72 hours → remove 4cm to protrude into
motility and viability o Tuboovarian abscess → remove IUD the vagina
o Septic abortion → uterine evacuation and antibiotics • An expelled or
o Common bacteria: Actinomyces partially expelled
▪ If asymptomatic → may retain her IUD device should not be
▪ If with signs of infection → remove reinserted
▪ Fever, weight loss, abdominal pain and abnormal uterine bleeding or discharge
• Pregnancy with an IUD
o If intrauterine and tail is seen → grasp and remove to reduce complications such as
abortion, chorioamnionitis and preterm birth
o If tail is not visible → attempts to remove it may result in abortion
Progestin Implant • Placed subdermally • Unscheduled bleeding • Active breast cancer • If no hormonal
Etonogestrel on medial surface of • Malpositioning – branches of medial antebrachial cutaneous nerve can be injured • Breast cancer disease contraception is used
Implant - Placed the upper arm 8- during implant or needle insertion that is too deep free > 5 years → insert within 5 days
subdermally on 10cm from elbow in • Cirrhosis of menses onset
medial surface of the biceps groove • Liver tumors • LNG: contraception is
the upper arm 8- and is aligned with established within 24
10cm from elbow in the long axis of the hours if inserted
the biceps groove arm within the first 7 days
and is aligned with • Can be used for 3 of mens
the long axis of the years • For transitioning →
arm; Can be used implant is placed on
for 3 years the day of first
Levonorgestrel placebo of COC; on
Implants: 5 years, 2 the day that the next
subdermally DMPA would be due
implanted rods or within 24 hours of
taking the last POP

91
Progestin Only • Suppress LH and • Irregular o heavy uterine bleeding → most frequently reported AE leading to • Current breast cancer • May be started
Contraceptives block ovulation discontinuation • Pregnancy immediately
• Cervical mucus is • Increased LDL and decreased HDL • Prior ectopic
thickened to retard • Excellent choice for lactating women pregnancy
sperm passage • Functional ovarian cysts develop with a greater frequency
• Endometrial atrophy
• Fertility is restored
rapidly following
cessation of
contraception
HORMONAL CONTRACEPTIVES
Combination • Suppression of hypothalamic gonadotropin releasing factors → block pituitary secretion of FSH and LH → no ovulation
Hormonal • Progestin component provides ovulation prevention by suppressing LH, thickens cervical mucus and endometrial atrophy
Contraceptives • Estrogen: block ovulation by suppressing FSH release, stabilizes endometrium which prevents intermenstrual bleeding
(CHC) • Interferes with release of GnRH from hypothalamus: MAJOR
Contains both • ESTROGEN: PREVENTS RISE IN FSH, ENHANCES EFFECT OF PROGESTIN
estrogen and • PROGESTIN: inhibits LH surge → ovulation inhibition, changes in cervical mucus prevents sperm transport, interferes with gamete transport, endometrium is thinned out
progestin and reduces likelihood of implantation → MAJOR MECH: INHIBITION OF FOLLICULAR DEVELOPMENT AND OVULATION
Combination Oral • Most frequently used reversible birth control method
Contraceptive • Ethinyl estradiol is the most common estrogen present in COC formulations
(COC) • Unwanted effects: breast tenderness, weight gain, nausea, headache
• Most progestins in COCs are testosterone related and impart androgenic SE such as acne and adverse HDL and LDL → to avoid this → antiandrogenic progestins have been
introduced → dienogest and nomegestrol acetate; drosperinone → also displays antiandrogenic activity, to minimize water retention and has antimineralocorticoid
properties (avoid in women with renal or adrenal insufficiency)
• Monophasic: progestin dose remains constant
• Biphasic, triphasic, quadriphasic: dose is frequently varied
• Administration:
o Taken at a specific time
o If 1 dose is missed → take missed pill, then scheduled dose is taken on time
o 2 or more: take most recent missed pill, take scheduled dose + effective barrier technique for 7 days while daily pills are continued
• In obese → COCs are effective but it increases VTE risk
• Alter lipid synthesis and raise level of TAGs and total cholesterol, HDL and VLDL → ESTROGEN LOWERS LDL
• Protein metabolism affected
o Fibrinogen and many of the clotting factors rise in direct proportion to the estrogen dose → thrombosis
o Angiotensinogen production is also augmented
o Elevate sex hormone binding globulin → lower concentrations of bioavailable testosterone and lessen androgenic side effects
• For nonsmoking women <35 → risk of stroke is low
Contraindications
• If with prior stroke or previous MI
• Risk for DVT and PE increased (estrogen dose related)
• VTE significantly increased >35yo who smoke
• Women within the first 4 weeks after delivery (postpartum increased risk for VTE)
• Active hepatitis

• Not associated with increased risk of cancer → protective effect against ovarian and endometrial ca
Transdermal Patch • A new patch is applied weekly for 3 weeks followed by a patch free week to allow withdrawal bleeding
• Risk for VTE is increased compared with COCs
Transvaginal Ring • Ring is constructed of ethinyl vinyl acetate
• Placed within 5 days of menses onset
• After 3 weeks of use it is removed for 1 week to allow withdrawal bleeding

92
Injectable progestin •
DMPA 150mg every 3 months
contraceptives •
Norethisterone enanthate 200mg every 2 months
•
Avoid massage after administration
•
Action: ovulation inhibition, greater cervical mucus viscosity, unfavorable endometrium
•
Administration: initial injection given within the first 5 days following menses
•
Quick start: initial preg test before injection and a supplemental contraceptive method during the 7 days following injection → second PT after 3-6 weeks to identify an
early pregnancy
• Has minimal to no lactation impairment
• Unique to DMPA: prolonged anovulation can follow discontinuation → delayed fertility resumption
• Weight gain is generally attributed to DMPA
• Loss of bone mineral density is a potential problem
• Bone loss is reversible after discontinuation of therapy → complete reversal after 18-24 months
Progestin Only Pills • Cervical mucus thickening and endometrial atrophy
• Mucus changes not sustained longer than 24 hours → must take at same time every day
• If taken 4 hours late → supplement form of contraception must be used for the next 48 hours
• Contraindicated: breast cancer and pregnancy
BARRIER METHODS: dual protection vs pregnancy and STI
Diaphragm + • Diaphragm is not removed for at least 6 hours after intercourse
spermicide • Associated with slightly greater risk of urinary infections from urethral irritation
Cervical cap • For contraception → must remain in place for 6 hours following coitus and may remain for up to 48 hours
Nonoxynol-9 • Do not provide additional protection against pregnancy or STI (it disrupts cell membranes epithelial disruption)
FERTILITY AWARENESS BASED METHODS – avoid sexual intercourse during the fertile phase; COUPLE MUST BE HIGHLY MOTIVATED (95-99% perfect use, 80-88% - typical use)
Lifespan of sperm: 5-6 days; Egg: 12-24 hours
A woman is fertile from 5 days before ovulation to 24 hours after ovulation
Standard days • Avoid unprotected sex during cycle days 8-19
method • Woman must have regular monthly cycles of 26-32 days
• Based on functional life span of sperm and egg and menstrual cycle physiology
Temperature • Relies on sustained 0.4F rise in basal body temp that precedes ovulation
rhythm method • Woman must abstain from sex from first day of menses through 3 rd day after temperature increase
• No intercourse from day 1 of menstrual cycle up to 3 days after temp rise of 0.2-0.5 degrees Celsius due to thermogenic effect of pregnanediol (from corpus luteum)
Cervical mucus • Evaluate cervical secretions several times each day, can be used by women with cycles <26 and >32 days
method “2 day • Relies on awareness of vaginal “dryness” and “wetness”
method” “Billings • Billings: abstinence is required from beginning of menses until 4 days after slippery mucus is identified; estrogen effect prior to ovulation; no intercourse on: days with
method” clear, wet, slippery, transparent or stretchy until 4 days
• 2 day method: intercourse is safe if a woman did not note mucus on the day of planned intercourse or the day prior → did I note secretions today and yesterday? → yes
→ you can get pregnant; you should have 2 consecutive days of no secretions
Symptothermal • Changes in cervical mucus (onset of fertile period)
method • Changes in basal body temp (end of fertile period)
• No intercourse from time you sense secretions or s/sx of ovulation until day 4 from peak of secretions, day 3 from BBT
SPERMICIDES: contain nonoxynol-9 or octoxynol-9; douching avoided for at least 6 hours after coitus
Contraceptive • Can be inserted up to 24 hours prior to intercourse and while in place it provides contraception regardless of coital frequency
Sponge • Should remain in place for 6 hours after intercourse
EMERGENCY CONTRACEPTION:
• Levonorgestrel is taken as a single, one time 1.5mg dose
• Dosing begins within 72 hours after unprotected coitus

93

CHAPTER 39
Sterilization
ACOG
Recommends consideration of salpingectomy to lower cancer risks
• Parkland method
• Pomeroy
• Salpingectomy
• Transcervical Sterilization
• Vasectomy:
o Vas deferens lumen is disrupted to block the
passage of sperm from the testes
o Non scalpel vasectomy accomplishes this with
one specialized instrument that grasps the vas
deferens and surrounding skin together
o Complete release of sperm stored in the
reproductive tract beyond the interrupted vas
deferens takes approximately 3 months or 20
ejaculations
o Failure most likely due to premature coitus
CHAPTER 40
Hypertensive Disorders
• Complicated 5-9% of all pregnancies
• Preeclampsia syndrome alone or superimposed on chronic
hypertension is the most dangerous
• Gestational hypertension: new onset hypertension during
pregnancy is followed by preeclampsia almost half the
time
DIAGNOSIS OF HYPERTENSIVE DISORDERS
• Diagnosed when appropriately taken blood pressure
exceeds 140 mmHg systolic or 90mmHg diastolic
• Sudden rise in mean arterial pressure but still in a normal
range → delta hypertension
• Delta Hypertension:
o Acute rise in blood pressure
GESTATIONAL HYPERTENSION
• BP 140/90mmHg
• Proteinuria not identified
PREECLAMPSIA SYNDROME
• BP >140/90
• Proteinuria – objective marker and reflects the system-
wide endothelial leak that characterizes preeclampsia
syndrome
• Epigastric or right upper quadrant pain frequently
accompanies hepatocellular necrosis, ischemia and edema
that stretches the Glisson capsule
o Accompanied by elevated AST and ALT
• Thrombocytopenia → signifies worsening preeclampsia
o Platelet activation and aggregation as well as
microangiopathic hemolysis
PREECLAMPSIA SUPERIMPOSED ON CHRONIC HYPERTENSION
• BP >140/90 before pregnancy or before 20 weeks AOG or
both
Clinical Risk Factors for Preeclampsia:
• SLE
• Nulliparity
• Age >35yo
• Prior stillbirth
• CKD
• ART
• BMI >30
• Multifetal
• Prior abruption
• Diabetes
• Prior preeclampsia
• Chronic hypertension
• APAS
Etiopathogenesis
• Gestational hypertensive disorders are more likely to
develop in women who:
o Exposed to chorionic villi for the first time
o Exposed to a superabundance of chorionic villi
(twins, H. mole)
o Have preexisting conditions associated with
endothelial cell activation or inflammation
(diabetes, obesity, CVD or renal disease,
immunological disorders or hereditary
influences)
o Genetically predisposed to hypertension
Phenotypic Expression of Preeclampsia Syndrome
• 2 major subtypes are differentiated by whether or not
remodeling of uterine spiral arterioles by endovascular
trophoblasts is defective
• “2 stage disorder”
o Stage 1: caused by faulty endovascular
trophoblastic remodeling that downstream
causes the stage 2 clinical syndrome
o Stage 2: preexisting maternal conditions that are
also manifest by endothelial cell activation or
inflammation
Etiology of Preeclampsia
• Placental implantation with abnormal trophoblastic
invasion of uterine vessels
• Immunological maladaptive tolerance between maternal,
paternal, and fetal tissues
• Maternal maladaptation to cardiovascular or inflammatory
changes of normal pregnancy
• Genetic factors
ABNORMAL TROPHOBLASTIC INVASION
• Normal implantation is characterized by extensive
remodeling of the spiral arterioles within the decidua
basalis
• Endovascular trophoblasts replace the vascular endothelial
and muscular lining to enlarge the vessel diameter
• Trophoblastic invasion may be incomplete → preeclampsia
• Diminished perfusion and a hypoxic environment →
placental debris or microparticle
• Changes incite a systemic inflammatory response (stage 2
of the preeclampsia syndrome)

94
IMMUNOLOGICAL FACTORS
• Women with molar pregnancies have a high incidence of Angiogenic • Placental vasculogenesis is evident by 21 days after
and conception
early-onset preeclampsia
Antiangiogen • Angiogenic imbalance: excessive amounts of
• Women with a trisomy 13 fetus: 30-40% incidence ic Proteins antiangiogenic factors simulated by worsening hypoxia at
• Due to elevated serum levels of antiangiogenic factors the uteroplacental interface
o Soluble fms like tyrosine kinase I on • Trophoblasts of preeclampsia women overproduce at
chromosome 13 least 2 antiangiogenic peptides
• Immune maladaptation → in women destined to be o Soluble fms-like tyrosine kinase 1 (sFlt1) is a
preeclamptic, extravillous trophoblasts early in pregnancy receptor for VEGF (vascular endothelial growth
express reduced amounts of immunosuppressive factor)
▪ Elevated sFlt1 levels inactivate and reduce
nonclassic human leukocyte antigen G (HLA-G) →
circulating free placental growth factor
contribute to defective placental vascularization in Stage 1 and VEGF concentrations → endothelial
of the preeclampsia syndrome dysfunction
• Th1 cells stimulate inflammatory cytokine secretion ▪ Soluble endoglin (sEng)
inhibits various
ENDOTHELIAL CELL ACTIVATION transforming growth factor
• Peroxidases generate highly toxic radicals → injure beta (TGF-B_ isoforms from
systemic vascular endothelial cells → modify nitric oxide binding to endothelial
receptors → diminished
production → interference with prostaglandin balance nitric oxide dependent
• Oxidative stress produces lipid-laden macrophage foam vasodilation
cells (seen in placental atherosis)
PATHOPHYSIOLOGY
GENETIC FACTORS
• 20-40% for daughters of preeclamptic mothers Pathophysiology
Cardiovascular • Greater cardiac afterload caused by hypertension
PATHOGENESIS system (related • Cardiac preload reduced by pathologically
to…) diminished volume expansion
Pathogenesi • Endothelial activation → intraendothelial
s extravasation of intravascular fluid into the
Vasospasm • Systemic endothelial activation causes vasospasm → extracellular space
elevates resistance to produce hypertension Hemodynamic • Cardiac output declines due to at least in part to
• Systemic endothelial cell injury → interstitial leakage and changes and greater peripheral resistance
blood constituents (platelets, fibrinogen) are deposited cardiac function • Consideration given to echocardiographic measures
subendothelially → endothelial junctional proteins are of myocardial function and relevant ventricular
disrupted → undergo ultrastructural change function
• With diminished blood flow because of maldistribution o Cardiac troponin levels are slightly elevated
from vasospasm and interstitial leakage → ischemia of and amino-terminal pro-brain natriuretic
surrounding tissues → necrosis, hemorrhage and other peptide are elevated
end-organ disturbances Blood volume • Hemoconcentration – hallmark of preeclampsia
Endothelial • Protein factors secreted into maternal circulation → • Women of average size have a blood volume of
cell injury activation and dysfunction of the systemic vascular 3000ml → 4500ml during the last several weeks of
endothelium normal pregnancy
• Intact endothelium as anticoagulant properties → injury • With eclampsia: 1500ml excess is lost from
→ less nitric oxide is produced → promotion of generalized vasospasm from endothelial activation
coagulation and greater sensitivity to vasopressors and leakage of plasma into the interstitial space
Increased • Enhanced reactivity to infused norepinephrine and • Vasospasm and endothelial leakage of plasma
pressor angiotensin II persist for a variable time after delivery as the
responses • Increased sensitivity to angiotensin II precedes onset of endothelium is restored to normalcy →
gestational hypertension vasoconstriction reverses → blood volume
• Several prostaglandins are thought to be central to reexpands → fall in hematocrit
preeclampsia syndrome Maternal • Over: platelet count <100,000
• Endothelial prostacyclin (PGI2) is low →mediated by thrombocytopenia • Platelet count may contribute to decline from the
phospholipase A2 first day and reaches normal levels within days 3-5
• Thromboxane A2 secretion by platelets is increased → Hemolysis • Accompanies severe preeclampsia → manifested by
prostacyclin: thromboxane A2 declines → greater increased LDH and reduced haptoglobin levels
sensitivity to infused angiotensin II → vasoconstriction • Derangements results from microangiopathic
• Nitric oxide – potent vasodilator from L-arginine by hemolysis caused by endothelial disruption with
endothelial cells → inhibited platelet adherence and fibrin deposition
• Endothelins ~ ET1 (21-amino acid peptides) – potent Coagulation • Elevated factor VIII consumption, increased levels of
vasoconstrictors changes fibrinopeptides A and B and D-dimers, reduced
• Plasma endothelins are elevated in normotensive levels of regulatory proteins antithrombin III and
pregnant women but with preeclampsia = higher levels proteins C and S
o MgSO4 lowers ET1 Endocrine and • Plasma levels of renin, angiotensin II, angiotensin 1-
hormonal 7, aldosterone, deoxycorticosterone and ANP are
alterations augmented in normal pregnancy
95
 • ANP released during atrial wall stretching from BV
expansion and responds to cardiac contractility
• Enhanced in women with preeclampsia
Fluid and • Volume of ECF is increased → edema
electrolyte • Mechanism for pathological fluid retention is
alterations endothelial injury
• Reduced plasma oncotic pressure → filtration
imbalance and displaces intravascular fluid into the
surrounding interstitium
• After eclamptic convulsion → serum pH and HCO3
are lowered due to lactic acidosis
Kidney • In a normal pregnancy → renal blood flow and GFT
rise
• With pre-eclampsia: renal perfusion and GFR are
reduced
• Glomerular endotheliosis – blocks the barrier that
allows filtration → increased creatinine
• Urine osmolality rises → urine: plasma creatinine is
elevated
• Proteinuria: 24 hr urine excretion >300mg, UPCR
>0.3, dipstick (1+~ 30mg/dL)
• Acute kidney injury: induced by hemorrhage with
hypovolemia and hypotension caused by severe
obstetrical bleeding coupled with inadequate blood
replacement
Liver • Characteristic hepatic lesions with eclampsia are
regions of periportal hemorrhage in the liver
periphery
• Pain is considered a severe disease
• Infarction may be worsened by hypotension from
obstetrical hemorrhage → hepatic failure / shock
liver
• Elevations of AST and ALT are markers for severe
preeclampsia → normalizes within 3 days following
delivery
• Hepatic hematoma – can extend to form a
subcapsular hematoma that may rupture → Tx:
observation
• Hallmark of acute fatty liver is significant liver
dysfunction
Brain • Cortical and subcortical petechial hemorrhages
• Endothelial cell dysfunction
• Response to acute and severe hypertension →
cerebrovascular overregulation leads to vasospasm
→ diminished cerebral blood flow → ischemia,
cytotoxic edema and tissue infarction
• Preeclampsia-associated intraendothelial cell leak
develops at blood pressure levels much lower than
those that cause vasogenic edema
• Autoregulation: mechanism by which cerebral blood
flow remains relatively constant despite alterations
in cerebral perfusion pressure – it protects the brain
from hyperperfusion when MAP rise to as high as
160mmHg
• Eclampsia occurs when cerebral hyperperfusion
forces capillary fluid interstitially because of
endothelial damage
• Cerebrovascular hyperperfusion has a predilection
for the occipital lobes → headaches and scotomas
• Excessive release of excitatory neurotransmitters
(esp glutamate) → convulsions
• Generalized cerebral edema may develop and is
usually manifest by mental status changes that vary
from confusion to coma
Uteroplacental • By the completion of placentation → impedance of
Perfusion uterine artery blood flow is markedly decreased
• With abnormal placentation → abnormally high
resistance persists
• Resistance in uterine spiral arteries → impedance
was higher in peripheral than in central vessels
PREDICTION
• Currently, no screening tests for preeclampsia are
predictably reliable, valid and economical
Vascular Resistance • Uterine artery doppler velocimetry is
Testing and Placental posited to reflect faulty trophoblastic
Perfusion invasion of the spiral arteries
• Failure results in diminished placental
perfusion and upstream greater uterine
artery resistance
Endothelial • Fibronectins are high molecular-weight
Dysfunction and glycoproteins released from endothelial
Oxidant stress cells and extracellular matrix following
endothelial injury
• Thrombocytopenia and platelet
dysfunction are integral features of
preeclampsia
PREVENTION
• Dietary manipulation: low salt diet, calcium or fish oil
• Exercise: physical activity, stretching
• Cardiovascular drugs: diuretics, antihypertensive drugs
• Antioxidants: ascorbic acid (vitamin C), vitamin E and D
o Metformin inhibits hypoxic inducible factor 1a by
lowering mitochondrial electron transport chain
activity
o Reduces sFlt-1 and sEng activity
• Antithrombotic drugs: low dose aspirin,
aspirin/dipyridamole, aspirin + heparin, aspirin +
ketanserin
o Low doses of 50-150mg daily to inhibits platelet
thromboxane A2, biosynthesis but has minimal
effects on vascular prostacyclin production
o Aspirin prophylaxis initiated by 16 weeks
associated with a significant risk reduction
o Low dose aspirin coupled with heparin mitigates
thrombotic sequelae in women with LAC
PREECLAMPSIA
One of the most important clinical questions for successful
management is precise knowledge of fetal age.
CONSIDERATION FOR DELIVERY
• Prime objective: forestall convulsions
• To prevent intracranial hemorrhage and serious damage to
other vital organs
• To deliver a healthy newborn
ECLAMPSIA
• Preeclampsia complicated by generalized tonic-clonic
convulsions appreciably raises the risk to both mother and
fetus
• Major maternal complications:
o Placental abruption – 10%
o Neurological deficits – 7%
o Aspiration pneumonia – 4%
o Acute renal failure – 4%
96
 • Other diagnosis should be considered in women with
convulsions more than 48 hours postpartum or in women
with focal neurological deficits
• Status epilepticus – require deep sedation and even
general anesthesia to obviate anoxic encephalopathy
• Respiratory rate after an eclamptic convulsion is usually
increased and may reach 50 or more per minute in
response to hypercarbia, lactic acidemia and transient
hypoxia
• Cyanosis in severe cases
• High fever – grave sign that emanates from
cerebrovascular hemorrhage
• Urine output may be diminished appreciably
• Pulmonary edema may follow after eclamptic convulsions
• Both pulmonary edema and hypertension can be further
aggravated by vigorous intravenous fluid administration
• All pregnant women with convulsions should be
considered to have eclampsia
MAGNESIUM SULFATE TO CONTROL CONVULSIONS
• It should not be overlooked that the IM and IV
• Not given to treat hypertension
• Exerts a specific anticonvulsant action on the cerebral
cortex
• Mother stops convulsing after the initial 4g loading dose
• When MgSO4 is given to arrest eclamptic seizures, 10-15%
of women will have a subsequent convulsion
• Parenterally administered MgSO4 is cleared almost totally
by renal excretion
• Magnesium intoxication is unusual when the GFR is normal
or only slightly reduced
• Serum crea must be measured to detect a decreased GFR
• 10mEq/L → patellar reflexes disappear
• >10mEq/L → breathing becomes weakened
• 12mEq/L → respiratory paralysis then arrest
• Treatment of mag toxicity: calcium gluconate or calcium
chloride 1g IV
• 4g loading dose can be safely administered regardless of
renal function
• Other effects:
o Reduced presynaptic release of the
neurotransmitter
o Blockade of glutamatergic N-methyl D aspartate
o Potentiation of adenosine action
o Improved calcium buffering by mitochondria
o Blockage of calcium entry via voltage-gated
channels
o In the uterus → high serum magnesium
concentrations depress myometrial contractility
both in vivo and in vitro
o Has small but significant effects on the FHR –
specifically beat to beat variability
o Protective effect against development of CP in
very low BW infants
MANAGEMENT CONSIDERATIONS
SEVERE HYPERTENSION MANAGEMENT:
• Lower systolic pressure to or below 160mmHg and
diastolic the bellow 110mmHg
• Long standing hypertension results in Charcot Bouchard
Aneurysm in the deep penetrating arteries of the
lenticulostriate branch of the MCA (supply basal ganglia,
putamen, thalamus and adjacent deep white matter)
• Hydralazine: 5-10mg initial dose → 10mg doses at 15029
minutes intervals until a satisfactory response is achieved
o Prevents: cerebral hemorrhage
o Onset of action: 10 minutes
• Labetalol: alpha and nonselective beta blocker
o Initial dose: 10mg → 10 minutes → 20mg → 10
minutes → 40mg
o If salutatory response not achieved: 80mg
o Recommendation: 20-40mg every 10-15
minutes as needed and a maximum of 220mg
per treatment cycle
o CONTRAINDICATED IN ASTHMATIC WOMEN
• Nifedipine:
o 10mg initial immediate release dose → 20-30
minutes → 10 to 20mg if necessary
o If not effective → give labetalol
o Sublingual not recommended
o Does not potentiate magnesium related effects
FLUID THERAPY
• LR at 60-125ml/her unless fluid loss is unusual from
vomiting, diarrhea, diaphoresis or excessive blood loss
with delivery
• Pulmonary edema:
o Most often happens during postpartum
o 3 common causes of pulmonary edema in severe
preeclampsia:
▪ Pulmonary capillary permeability
edema
▪ Cardiogenic edema
▪ Combination
PERSISTENT SEVERE POSTPARTUM HYPERTENSION
• Chronic but not sporadic administration of NSAIDs
(ibuprofen) may aggravate postpartum hypertension in
those with preeclampsia
• Furosemide – hastens BP control
• Measure excessive extracellular interstitial fluid
o Postpartum weight is compared with most
recent prenatal weight
o Typically soon after delivery → maternal weight
is reduced at least 10-15 lbs.
o In severe preeclampsia – weight in excess of
their last prenatal weight
LONG TERM CONSEQUENCES
Future • Nulliparas diagnosed with pre-ec before 30
pregnancies weeks → recurrence: 40%
Long term • Hypertension attributable to pregnancy
morbidity and should resolve within 12 weeks
mortality • If >12 weeks → chronic hypertension
Cardiovascular • Ischemic heart disease: 24%
morbidity
97
 arrest bleeding from vessels at the placental implantation
site
• Duncan mechanism: Blood from the implantation site may
escape into the vagina immediately
• Schultze mechanism: blood remains concealed behind the
placenta and membranes until the placenta is delivery
• Manual extraction of placenta → give ampicillin or
cefazolin prophylaxis
• Oxytocin never given as an undiluted bolus dose because
of serious hypotension or cardiac arrythmias

CHAPTER 41 RISK FACTORS

• Primiparity
• High parity
Obstetrical Hemorrhage • Prior postpartum hemorrhage

• Single most important cause of maternal death worldwide EVALUATION AND MANAGEMENT
• Uterotonic agents:
GENERAL CONSIDERAITONS o Oxytocin
• With placental separation, the vessels at implantation site o Ergot derivatives as second line
are avulsed and hemostasis is achieved first by myometrial ▪ Rapidly stimulate tetanic uterine
contraction contractions for approximately 45
• PPH – loss of >1000ml blood loss + symptoms of minutes
hypovolemia ▪ 0.2mg IM and can be repeated at 2-4
• EBL is only approximately half of the actual loss hour intervals needed
• Normal pregnant woman tolerates, without any decrease ▪ May cause dangerous hypertension
in postpartum hematocrit, blood loss at delivery that o E and F series prostaglandins
approaches the volume of blood that she added during Agent Dose SE CI
Carboprost: 250ug Diarrhea Asthma
pregnancy
15-methyl (0.25mg) HPN Suspect AF
• Whenever the PP hematocrit is lower than the one derivatives given IM Vomiting embolism
obtained on admission → blood loss can be estimated as: of Can be Fever
calculated pregnancy added volume + 500ml for each 3 prostaglandi repeated Flushing
volume percent decline of the hematocrit n F2a as Tachycardi
• 6% drop in PP hematocrit = clinically significant blood loss necessar a
with vaginal delivery y with Pulmonary
15-90 and
minute vascular
intervals constrictio
to a max n
of 8
doses

Dinoproston 20mg Diarrhea Hypotensio

e– supp per n
prostaglandi rectum
n E2 or vagina
TIMING Q2
• Antepartum – placenta previa or abruptio Bleeding unresponsive to Uterotonic Agents
• Postpartum – uterine atony or lacerations 1. Begin bimanual uterine compression
Postpartum Hemorrhage 2. Immediately mobilize emergent care obstetrical team to
• Uterine atony with placental site bleeding, genital tract DR and call for whole blood or packed RBC
trauma or both 3. Urgent help from anesthesia
• Expanding vulvar or vaginal hematoma 4. Secure at least 2 large bore IV
• Persistent bleeding despite a firm, well contracted uterus 5. Begin volume resuscitation with crystalloids
→ lacerations
• Late postpartum hemorrhage: bleeding after the first 24 • Balloon tamponade (Bakri balloon)
hours • Surgical procedure – uterine compression, pelvic vessel
ligation, angiographic embolization, hysterectomy
UTERINE ATONY
THIRD STAGE LABOR MANAGEMENT UTERINE INVERSION
• Most frequent cause of obstetrical hemorrhage is failure of Risk Factors
the uterus to contract sufficiently after delivery and to • Fundal placental implantation
• Uterine atony

98
 • Cord traction applied before placental separation
• Abnormally adhered placentation (accreta)
Surgical Intervention
• Application of atraumatic clamps to each round ligament
and upward traction – Huntington procedure
• Haultain incision: if a constriction ring still prohibits
repositioning → a sagittal surgical cut is made posteriorly
through the muscular ring to release it → exposed fundus
can then be reinverted
INJURIES TO THE BIRTH CANAL
CERVICAL LACERATIONS Risk Factors:
• Cervix may be entirely or partially avulsed from the vagina
in the anterior, posterior or lateral fornices → colporrhexis
• Annular or circular detachment: entire vaginal portion of
cervix is avulsed
Risk factors:
• Forceps delivery through an incompletely dilated cervix
with the blades applied over the cervix
• 1-2cm lacerations are not repaired unless bleeding
PUERPERAL HEMATOMAS
• Vulvar hematomas may involve the vestibular bulb or
branches of the pudendal artery (inferior, rectal, perineal
and clitoral arteries)
• Paravaginal hematomas may involve the descending
branch of the uterine artery
Risk factors:
• Vaginal or perineal laceration
• Episiotomy
• Operative delivery
Diagnosis
• Excruciating pain
• Tender, tense swelling of varying size rapidly develops
UTERINE RUPTURE
• Primary: occurring in a previously intact or unscarred Clinical Findings and diagnosis
uterus
• Secondary: associated with preexisting incision, injury or
anomaly to the myometrium
• Additional risks for rupture include other previous
operations or manipulations that traumatize the
myometrium (curettage, perforation, endometrial
ablation, myomectomy or operative hysteroscopy)
Hypovolemic shock
Pathogenesis:
• Thinned out lower uterine segment
• When the rent is immediate vicinity of the cervix → Consumptive
extends transversely or obliquely coagulopathy
• When the rent forms in the portion of the uterus adjacent
to the broad ligament → longitudinal
PLACENTAL ABRUPTION
Etiopathogenesis:
• Abruption likely begins with a rupture of a decidual spiral
artery and then an expanding retroplacental hematoma
• External hemorrhage: bleeding escaping through the cervix
• Concealed hemorrhage: blood is retained between the
detached placenta and the uterus
• Severe abruptio:
o Maternal sequala that include DIC, shock,
transfusion, hysterectomy, renal failure or death
o Fetal complications: NRFS, growth restriction or
death
o Neonatal outcomes: death, preterm delivery or
growth restriction
• Prior abruptio
o Term abruptios tend to be recurrent
o Labor induction at 37 weeks
• Increased age and parity
• Hypertensive disorders
o Some form of hypertension is the most frequent
condition associated with abruptio
o CHVD with superimposed PE with fetal growth
restriction → greater risk
• Chorioamnionitis
• PROM
o Risk is further increased with comorbid infection
o Inflammation and infection lead to abruptio
• Multifetal gestation
• Low birthweight
• Hydramnios
• Cigarette smoking
o 5 to 8fold risk
• Single umbilical artery
• Cocaine use
• Uterine leiomyoma – especially if located near mucosal
surface behind the placental implantation site
• Most women with a placental abruptio have sudden onset
abdominal pain, vaginal bleeding and uterine tenderness
• With abruptio, some degree of intravascular coagulation is
almost universal
• Elevated serum levels of D-dimers may be suggestive
Clinical Finding Characteristics
• Caused by maternal blood loss
• Prompt treatment of hypotension with
crystalloid and blood infusion is essential
• Defibrination syndrome: consumptive
coagulopathy or DIV → intravascular activation
of clotting
• Abruptio is the most common cause of clinically
profound consumptive coagulopathy in OB
• Activation of plasminogen to plasmin → lyses
fibrin microemboli o maintain microcirculatory
patency
• With abruptio there are always pathological
levels of fibrinogen-fibrin degradation products
and D-dimers in maternal serum
• Consumptive coagulopathy more likely with a
concealed abruptio because intrauterine
pressure is higher → forces more thromboplastin
into the large veins draining the implantation site
99
Couvelaire uterus • Widespread extravasation of blood into the
uterine musculature
• AKA uteroplacental apoplexy
End organ injury • Delayed or incomplete Tx of hypovolemia with
severe placental abruptio
• Risk for renal injury is magnified when
preeclampsia coexists
• Rarely – pituitary failure Sheehan syndrome
follows severe intrapartum or early PPH
MANAGEMENT
• 20 minute decision-to-delivery interval
• If fetus died → vaginal delivery
PLACENTA PREVIA
• With greater blood flow in the upper uterus, placental
growth is more likely directed toward the fundus –
trophotropism
• A low lying placenta or placenta previa is less likely to
migrate if there is a prior cesarean delivery scar
Classification:
• Placenta previa: internal os is covered partially or
completely by the placenta
• Low lying placenta: implantation in the lower uterine
segment where the placental edge does not cover the
internal os but lies within a 2cm wide perimeter around
the os
Risk Factors
• Maternal age
• Multiparity
• Cigarette smoking
• One or more prior cesarean deliveries
• Maternal serum alpha-fetoprotein (MSAFP) levels
abnormally elevated
• ART
Clinical Features
• Sentinel bleed: bleeding from a previa without warning
and without pain or contractions in a woman who has had
an uneventful prenatal course
• Coagulation defects are rare complications o previa even
when implantation site separation is extensive
• If placental location remains in question, TVS is the most
accurate method of assessment
• Restriction of activity is not necessary unless a previa
persists beyond 28 weeks or if clinical findings (bleeding,
contractions) develop before this time
• At 32 weeks AOG if placental edge is still <2cm from the os
→ TVS is repeated at 36 weeks
Management
• After bleeding has ceased for approximately 2 days and
the fetus is judged to be healthy, a woman can usually be
discharged home with instructions for “pelvic rest”
• NIH: Elective delivery at 36-37 weeks
• SMFM: Delivery between 34-37 weeks
• With a morbidly adherent placenta → delivery at 34-35
weeks
Hysterectomy
• Placenta previa with accreta is the most frequent
indication for peripartum hysterectomy
MORBIDLY ADHERENT PLACENTA
• Aberrant placentation characterized by abnormally
implanted, invasive or adhered placenta
• Stems in part from partial or total absence of the Nitabuch
layer
• Decidual deficiency prevents normal placental separation
after delivery
• Myometrial fibers attached to the basal plate in an
antecedent pregnancy are predictive markers for a
subsequent placenta accreta
Classification:
• Accreta: villi are attached to myometrium
• Increta: villi actually invade the myometrium
• Percreta: villi penetrate through the myometrium and to
or through the serosa
• Total placenta accreta: involvement of all lobules
• Focal accreta: part of a single lobule or a lobule is attached
Incidence:
• In subsequent pregnancies following accreta → recurrence
is high
Risk Factors:
• 2 most important risk factors: associated previa and a prior
cesarean delivery
Clinical Presentation and Diagnosis
• Better results with 3d and power doppler
Management
• Delivery between 34-37 weeks
• Criteria for Consideration of Delivery in an Accreta
o Suspicion for morbidly adherent placenta on
sonogram
o Previa with abnormal ultrasound appearance
o Placenta previa with >3 prior cesarean deliveries
o Prior classical cesarean delivery and anterior
placentation
o Prior endometrial ablation or pelvic irradiation
o Inability to adequately evaluate or exclude
placenta accreta
o Any other reason to suspect morbidly adherent
placenta
• Cesarean delivery hysterectomy: after fetal delivery, the
extent of placental invasion is assessed without attempts
at manual placental removal
OBSTETRICAL COAGULOPATHIES
• Actual consumption of procoagulants within the
intravascular tree → consumptive coagulopathy
• Massive loss of procoagulants from hemorrhage →
dilutional coagulopathy
DIC • second most common severe maternal
morbidity indicator
• associated with nearly a fourth of maternal
deaths
Pregnancy • extensive changes in coagulation and
induced fibrinolysis develop to create a procoagulant
coagulation state
changes • increase in plasma concentrations of factors I
(fibrinogen), VII, VIII, IX and X
• plasminogen levels rise but levels of
100
 plasminogen activator inhibitor 1 and 2 (PAI-
1, PAI-2) grow → plasmin activity declines
until delivery
• mean platelet count drops by 10% during
pregnancy and platelet activation is
enhanced
• net result → greater levels of fibrinopeptide
A, beta thromboglobulin, platelet factor 4
and fibrinogen-fibrin degradation products
(includes D-dimers)
• augmented yet compensated intravascular
coagulation to maintain uteroplacental
interface
• lower concentrations of anticoagulant
protein S, hypercoagulability and decreased
fibrinolysis
ACTIVATION OF NORMAL COAGULATION
Tissue factor initiates coagulation and forms complexes with factor
VII/VIIa to activate factors IX and X → generate Factor X (Xa) to
initiate clotting → initial thrombin activates factor XI (via feedback
amplification loop) → fibrin formation → counterbalanced by the
fibrinolytic system → plasminogen activated → production of
fibrinogen / fibrin degradation products like D-dimers
Activation of Pathological Coagulation:
Initiation of DIC begins with release of tissue factor by pathological
entities → tissue factor is released by subendothelial tissue and
stimulated monocytes → release cytokines from endothelium →
generalized endothelial activation → diffuse activation of
coagulation
• Becomes significant when coagulation factors and
platelets are sufficiently depleted → consumptive
coagulopathy
• Best known cause: abruptio (because it releases
thromboplastin)
DIAGNOSIS
• Bioassay – excellent method to detect or suspect
significant coagulopathy
• Thrombocytopenia is likely if petechia are abundant or if
clotted blood fails to retract within an hour
o Low platelet count
o Prothrombin time and partial thromboplastin
time prolongation may stem from low fibrinogen
concentrations → reduced levels of
procoagulants needed to generate thrombin
GENERAL MANAGEMENT:
• Rapid replacement of procoagulants is indicated
• Placental abruptio is the most common cause of severe
consumptive coagulopathy
• Preeclampsia, eclampsia and HELLP syndrome →
endothelial activation is a HALLMARK
FETAL DEATH AND DELAYED DELIVERY
With singleton pregnancies, if the dead fetus is undelivered, most
women enter spontaneous labor within 2 weeks. Gross disruption of
maternal coagulation rarely develops before 4 weeks. After 1 month,
almost ¼ will develop consumptive coagulopathy.
Amnionic Fluid Embolism
• Classic triad of abrupt hemodynamic and respiratory
compromise along with DIC
Predisposing Conditions:
• Rapid labor
• Meconium stained fluid
• Tears into uterine and other large pelvic veins that permit
an exchange of fluids between maternal and fetal
compartment
Risk Factors:
• AMA
• Post term pregnancy
• Labor induction or augmentation
• Eclampsia
• CS
• Forceps / vacuum
• Placental abruptio or previa
• Hydramnios
Diagnosis of AF embolism:
• Woman in the late stages of labor or immediately
postpartum begins gasping for air → seizures or
cardiorespiratory arrest rapidly follows + massive
hemorrhage → consumptive coagulopathy
DIAGNOSTIC CRITERIA FOR AF EMBOLISM (CAN-D)
Clinical onset during labor or within 30 minutes of placental delivery
Abrupt onset of cardiorespiratory arrest or both hypotension and
respiratory compromise
No fever >38 degrees
Documentation of overt DIC (must be detected prior to loss of
sufficient blood to cause dilutional or shock related consumptive
coagulopathy)
Pathogenesis of AF embolism:
• Total disruption of maternal-fetal interface → materials
from fetal compartment enter maternal circulation →
abnormal activation of proinflammatory mediator systems
(like in SIRS) → initial, transient pulmonary
vasoconstriction and hypertension → acute right
ventricular failure → hemodynamic collapse from right
ventricular infarction + interventricular septum
displacement of left and decreased left sided cardiac
output → cardiogenic pulmonary edema and systemic
hypotension → acute respiratory failure with severe
hypoxemia from shunting
• Material from fetal compartment containing tissue factor
activates factor VII → DIC
Management:
• Suitable goal for temperature is 36 degrees Celsius
• Mean arterial pressure: 65mmHg
• Survivors commonly have profound neurological
impairment
Other Causes of Obstetrical Coagulopathies
Sepsis syndrome: E. coli bacteremia is frequently seen with
antepartum pyelonephritis and puerperal infections
• S pyogenes, S aureus or C. perfringens, C. sordellii, or C.
novyi
Purpura Fulminans: microthrombi in small BV leading to skin
necrosis and sometimes vasculitis
• Usually complicated sepsis in women with heterozygous
protein C deficiencies and low protein C serum levels
101
Abortion: septic abortion can incite coagulation and worsen
hemorrhage especially with midtrimester abortions
• Can stimulate intravascular coagulation even in the
absence of sepsis
MANAGEMENT OF HEMORRHAGE
• 500ml loss for each 3 volume percent drop in hematocrit
• With acute blood loss → real time hematocrit is at its
maximum whenever measured in the delivery, operating
or recovery room
• Urine output is measured hourly
• Urine flow of at least 30ml and preferably >50ml per hour
Hypovolemic Shock
• Mean arterial pressure, stroke volume, cardiac output,
central venous pressure and pulmonary capillary wedge
pressure decline
• Blood flow to capillary beds in various organs is controlled
by arterioles
• Catecholamine release during hemorrhage prompts
greater venular tone → autotransfusion from this
capacitance reservoir
• Compensatory rises in heart rate, systemic and pulmonary
vascular resistance and myocardial contractility
• Cardiac output and blood volume are redistributed from
the effect of selective, centrally mediated arteriolar
constriction or relaxation
• Relatively more blood flow is diverted to the heart, brain
and adrenal glands
• When blood volume deficit exceeds approximately 25% →
compensatory mechanisms usually are inadequate to
maintain cardiac output and BP
• Maldistribution of blood flow results in local tissue hypoxia
and metabolic acidosis → vasoconstriction, organ ischemia
and cellular death
• Activation of lymphocytes and monocytes → endothelial
cell activation and platelet aggregation
• Survival is enhanced in acute hemorrhagic shock if blood
plus crystalloid solution is given compared with BT alone
Blood Replacement
• With ongoing obstetrical hemorrhage → rapid blood
infusion when the hematocrit is <25%
• Compatible whole blood is ideal for treatment of
hypovolemia from catastrophic hemorrhage
• One unit raises hematocrit by 3-4%
• Preferable use of whole blood for massive hemorrhage
• In the woman with obstetrical hemorrhage → platelet
count should be maintained >50,000 /uL by the infusion of
platelet concentrates
• Fibrinogen level <150 mg/dL or a sufficiently prolonged PT
or PTT in a woman with surgical bleeding is an indication
for replacement
• Alternative: Fresh frozen plasma administered in doses of
10-15ml/kg or cryoprecipitate
Dilutional Coagulopathy
• A major drawback of treatment for massive hemorrhage
with crystalloid solutions and packed RBC is depletion of
platelets and clotting factors → dilutional coagulopathy
• Thrombocytopenia – most frequent coagulation defect
found with blood loss and multiple transfusions
Blood Products
Blood Product
Packed RBC 1 unit is derived from 1 unit of whole blood
to have a hematocrit of 55-80 volume %
1 unit will increase Hct by 3-4 vol %
Platelets When platelet count falls below 50,000/uL
Equivalent of six units from six individual
donors
Raises platelet count by approx. 20,000/uL
Fresh frozen plasma 30 minutes to thaw
Source of all stable and labile clotting
factors including fibrinogen
Often used for treatment of consumptive or
dilutional coagulopathy
Not appropriate for use as a volume
expander in the absence of clotting factor
deficiencies
Should be considered in a woman with a
fibrinogen level <150 or with abnormal PT
or PTT
Cryoprecipitate Each unit is prepared from one unit of FFP
Each 10 to 15ml unit contains at least
200mg of fibrinogen along with factor
VIII:C, factor VIII: von Willebrand, factor XIII
and fibronectin
Ideal source of fibrinogen when levels are
dangerously low and there is oozing
Each gram raises plasma fibrinogen approx.
40mg/dL
Recombinant Binds to exposed tissue factor at the site of
activated factor VII injury to generate thrombin that activates
platelets and the coagulation cascade
Will not be effective if plasma fibrinogen
level is <50mg/dl or platelet count is
<30,000/uL
Tranexamic acid Antifibrinolytic drug used for traumatic and
obstetrical hemorrhage
Inhibits clot lysis to help forestall bleeding
by preventing plasmin from degrading fibrin
TRANSFUSION COMPLICATIONS:
• Transfusion of an incompatible blood component → acute
hemolysis → DIC, acute kidney injury and death
102
• Fever, hypotension, tachycardia, dyspnea, chest or back
pain, flushing, severe anxiety and hemoglobinuria
• Transfusion related acute lung injury (TRALI): most
common cause of transfusion related mortality
o Severe dyspnea, hypoxia, noncardiogenic
pulmonary edema within 6 hrs of transfusion
• Bacterial infection – most common: Yersinia,
Pseudomonas, Serratia, Actinobacter and Escherichia

103
 PPROM
CHAPTER 42 Molecular changes Spontaneous rupture before 37 weeks
Risk factors:
• Lower socioeconomic status
Preterm Birth • BMI <198
• Small for gestational age categorizes newborns whose • Nutritional deficiencies
birthweight is <10th percentile for gestational age • Smoking
• Appropriate for gestational age: 10th-90th percentile Enhanced risk of recurrence during a
• Large for gestational age: >90th percentile subsequent pregnancy
Most tensile strength of the membranes is
provided by the amnionic extracellular matrix
Major Short and Long Term Problems in Very Low BW Infants
and interstitial amnionic collagens that are
Organ/System Short-Term Probs Long Term Probs
produced in mesenchymal cells → collagen
Pulmonary RDS, air leak, Bronchopulmonary degradation
bronchopulmonary dysplasia, reactive airway
With membrane rupture → thrombin activity
dysplasia, apnea of disease, asthma rises → activates MMP and prostaglandins
prematurity Oxidative stress by events other than infection
GI Hyperbilirubinemia, feeding Failure to thrive, short- → DNA damage → premature senescence →
intolerance, NEC, growth bowel syndrome, subsequent inflammation → proteolysis →
failure cholestasis PPROM
Immuno Hospital acquired infection, RSV, bronchiolitis Infection Inflammatory response → membrane
immune deficiency, weakening
perinatal infection
Multifetal Pregnancy
CNS IVH, PVL, hydrocephalus Cerebral palsy,
Twins Effect of uterine stretch
hydrocephalus, cerebral
atrophy, ND delay,
hearing loss CONTRIBUTING FACTORS
Ophtha Retinopathy of prematurity Blindness, retinal
detachment, myopia Contributing Factor Features
CVS Hypotension, PDA, Pulmonary hypertension, Pregnancy factors Threatened abortion in early
pulmonary hypertension HPN in adulthood pregnancy → higher rates of
Renal Water and electrolyte HPN in adulthood later adverse outcomes
imbalance, acid base
Lifestyle Smoking, inadequate maternal
disturbances
Hematologic Iatrogenic anemia, need for weight gain and illicit drug use,
frequent BT, anemia of young or AMA, poverty, short
prematurity stature and vitamin C deficiency
Endo Hypoglycemia, transiently Impaired glucose Genetic factors Immunoregulatory genes
low thyroxine levels, cortisol regulation, increased potentiate chorioamnionitis in
deficiency insulin resistance cases of preterm delivery due to
infection
CAUSES OF PRETERM BIRTH Periodontal disease Chronic anaerobic inflammation
associated with preterm birth
Spontaneous Preterm Labor Interval between pregnancies <18 months and >59 months:
Cause Details greater risks for both preterm
Uterine distention Contraction associated proteins in the
birth and SGA
myometrium influenced by stretch
Maternal-Fetal stress Nutrient restriction, obesity, infection, diabetes
Prior preterm birth MOST IMPORTANT RISK
Elevations in cortisol form maternal FACTOR
psychological stress 3fold greater than women
Cervical dysfunction Cervical remodeling precedes premature labor whose 1st neonate was born at
onset term
Infection Bacteria gain access to intrauterine tissues Influenced by: frequency of
through: prior preterm, deliveries,
1. Transplacental transfer of maternal severity as measured by GA and
systemic infection
the order in which the prior
2. Retrograde flow of infection into
the peritoneal cavity via FT
preterm delivery occurred
3. Ascending infection with bacteria Infection Antibiotic prophylaxis to
from vagina and cervix prevent preterm birth is not
Inflammatory Responses Lipopolysaccharide (LPS) or other toxins from recommended
bacteria are recognized by pattern recognition Bacterial vaginosis Nugent score or Amsel criteria
receptors (toll-like receptors) → activation → Associated with spontaneous
signaling cascade → production of chemokines abortion, PTB PPROM,
IL-8 and cytokines IL-1Beta → promotes
chorioamnionitis and AF
prostaglandin release → cervical ripening
Most common: G. vaginalis, U. urealyticum embolism

104

PRETERM BIRTH PREVENTION
CERCLAGE:
• My benefit women who have a history of recurrent
midtrimester losses and who are diagnosed with cervical
insufficiency
• Woman noted to have a short cervix → rescue cerclage
• Short cervix <25mm
• Women with a singleton pregnancy, prior spontaneous
preterm birth before 34 weeks, cervical length <25mm and
GA <24 weeks → consider cerclage
• Effective in lowering RDS and neonatal mortality rates if
birth was delayed for at least 24 hours after initiation of
betamethasone
• Beta and dexa are equivalent
ACOG
Because treatment for less than 24 hours may be beneficial and
reduce neonatal morbidity and mortality, a first dose of antenatal
corticosteroids administered regardless of the ability to complete
additional doses before delivery is recommended
Consideration for administration of a single course of
betamethasone for women between 34-35 5/7 weeks has been
recommended by ACOG and Society of MFM

PROPHYLAXIS WITH PROGESTOGEN COMPOUNDS TOCOLYSIS TO TREAT PRETERM LABOR

• Progesterone withdrawal is considered to be a parturition
triggering event Classification Brand Mode of Action /
• Use of 17-OHP-C rather than vaginal progesterone for Recommendation
prevention of recurrent preterm birth Beta Terbutaline Only short term inpatient use
o Synthetic progestogen adrenergic Acute therapy for uterine
o Predominantly mediated by the CYP3A Receptor tachysystole
ACOG Agonists 0.25mg
Universal cervical length screening in women without a prior Mag sulfate Calcium antagonist
preterm birth is not mandatory 4g loading dose → 2g/hr
WOF: edema!
MANAGEMENT OF PPROM Prostaglandin Indomethacin Use 24-48 hrs because of
inhibitors (nonselective concerns of oligo which can
GA MANAGEMENT cyclooxygenase develop with therapeutic doses
>34 weeks Plan delivery inhibitor)
Labor induction unless contraindicated Nitric oxide Nitroglycerin Orally, transdermally, or IV was
Group B strep prophylaxis donors ineffective
Single corticosteroid course up to 36 6/7 Calcium Nifedipine Myometrial activity is directly
32-33 weeks Expectant management channel related to cytoplasmic free
Group B strep prophylaxis blockers calcium → block → inhibits
Single corticosteroid course contractions
Antimicrobials to prolong latency Enhances NM blocking effects
24-31 weeks Expectant management of magnesium which can
Group B strep prophylaxis interfere with pulmonary and
Single corticosteroid course cardiac functions
Tocolytics: no consensus Oxytocin Atosiban Has concerns on efficacy and
Antimicrobials to prolong latency receptor fetal-newborn safety
MgSO4 for neuroprotection antagonist
<24 weeks Expectant management or induction of labor
Single course corticosteroid may be REMINDER! ☺
considered Fetal tachycardia especially with ruptured membranes is suggestive
Antibiotics may be considered of sepsis.

Clinical Chorioamnionitis
• Fever is the only reliable indicator for diagnosis
• When maternal temp is >39 degrees or when maternal
temp is 38-39 degrees, and one additional clinical risk
factor is present
Antibiotic Therapy
• Ampicillin + erythromycin every 6 hrs from 48 hrs →
amoxicillin + erythromycin every 8 hours for 5 days
• Co-Amox not used due to incidence of NEC
Corticosteroids
• 24-34 weeks AOG → recommended
Corticosteroids for Fetal Lung Maturation
CHAPTER 43
Post Term Pregnancy
• Exceeds 42 weeks – 294 days or more from the first day of
the last menstrual period
ESTIMATED GESTATIONAL AGE
• First trimester sonography to be the most accurate
method to establish or confirm gestational age
INCIDENCE
• Only prepregnancy BMI >25 and nulliparity were
significantly associated with prolonged pregnancy

105
 • Maternal genes influenced prolonged pregnancy
• Rare fetal-placental factors that predispose to post term
pregnancy – anencephaly, adrenal hypoplasia, X-linked
placental sulfatase deficiency

PATHOPHYSIOLOGY:
• Placental dysfunction
o Associated skin changes were due to loss of the
protective effects of vernix caseosa
CHAPTER 44
o Rate of placental apoptosis – programmed cell
death – is significantly greater at 41-42 weeks Fetal Growth Disorders
compared with 36-39 weeks
o Kisspeptin are upregulated in post term FETAL GROWTH
placental explants compared with the same Divided into 3 phases
genes in term placental explants • Hyperplasia: first 16 weeks → rapid increase in cell
o Fetal oxygenation was decreased in some post number (5g/d at 15 weeks)
term gestations • Cellular hyperplasia and hypertrophy: extend up to 32
• Fetal Distress and Oligohydramnios weeks (15-20g/d at 24 weeks)
o Volume of amnionic fluid normally continues to • Cellular hypertrophy: after 32 weeks, fetal mass accrues
decline after 38 weeks and may become → most fetal fat and glycogen are accumulated (30-35g/d
problematic at 34 weeks)
• Fetal Growth Restriction Other hormones implicated in fetal growth:
o Stillbirths were more common among growth • Adipokines – leptin, the protein product of the obesity
restricted newborns who were delivered after 42 gene
weeks • Fetal growth is also dependent on an adequate supply of
nutrients
COMPLICATIONS:
• Placental fatty acid metabolism and transfer may be
• Oligohydramnios dysregulated in fetal growth restriction and in maternal
• Macrosomia conditions associated with fetal overgrowth
o Velocity of fetal weight gain peaks at • Levels of endothelial lipase are reduced with deficient fetal
approximately 37 weeks growth → overexpressed in placentas of women with
o Brachial plexus injury not related to post term diabetes
gestation
o In the absence of diabetes, vaginal delivery is not
FETAL GROWTH RESTRICTION
contraindicated for women with an EFW up to
5000grams
Symmetrical Asymmetrical
INDUCTION VERSUS FETAL TESTING • Proportionally small • Disproportionately
• Induction after 41 weeks rather than surveillance was • Early insult → lagging abdominal
decrease in cell growth compared with
associated with significantly fewer perinatal deaths and
number and size head growth
meconium aspiration syndrome cases and a lower
cesarean delivery rate • Chemical exposure, • Follows a later
pregnancy insult
• Labor induction at 42 weeks has a higher CS delivery rate viral infection, cellular
compared with spontaneous labor maldevelopment with • Placental insufficiency
aneuploidy from hypertension
MANAGEMENT STRATEGIES • Genetically • Disordered growth
• When AOG is uncertain, ACOG recommends delivery at 41 determined small
weeks using the best clinical estimate of gestational age stature

Brain Sparing:
• Ratio of brain weight to liver weight during the last 12
weeks (3:1)
o May be increased to 5:1 or more in severely
growth restricted infants
• Somatic growth restriction results from preferential
shunting of oxygen and nutrients to the brain

Placental Abnormalities
• Atrial natriuretic peptide converting enzyme AKA corin
plays a critical role in trophoblastic invasion and
remodeling of the spiral arteries

106
Perinatal Morbidity and Mortality
• Rates of stillbirth and adverse neonatal outcomes (birth
asphyxia, meconium aspiration, hypoglycemia and
hypothermia, neurological development) are all increased
• Risks of adverse neurodevelopmental outcomes are
substantial
Long Term Sequelae
• Fetal Undergrowth
o Suboptimal fetal nutrition and an increased risk
of subsequent adult hypertension,
atherosclerosis, type 2 DM and metabolic
derangement
• Fetal Overgrowth
o Increased interventricular septal thickness in
neonates of mothers with gestational diabetes
→ obesity, diabetes
Accelerated Lung Maturation
• Fetus responds to a stressed environment by augmenting
adrenal glucocorticoid secretion → accelerated fetal lung
maturation
Risk Factors and Etiologies
• Malaria (protozoal infection) causes fetal growth
restriction
• Gestational Weight Gain and Nutrition
o Food restriction to <1500 kcal/day adversely
affects fetal growth minimally
o Supplementation of iron and folic acid improved
birth outcomes
o Exercise reduces the risk of fetal overgrowth
without raising the risk of poor growth
• Vascular and Renal Disease
o Chronic vascular disease commonly causes
growth restriction esp when complicated by
superimposed preeclampsia
• Pregestational Diabetes
o Fetal growth restriction in newborns of women
with diabetes may be related to congenital
malformations or may follow substrate
deprivation from advanced maternal vascular
disease
o Women with type 1 → less likely to deliver an
SGA newborn
• APAS
o FGR associated with three types of APAS:
▪ Anticardiolipin antibodies
▪ Lupus anticoagulant
▪ Anti-beta 2 glycoprotein I antibodies
o 2 hit hypothesis: initial endothelial damage →
intervillous placental thrombosis
o Outcomes may be poor and include FGR and
demise
o Primary autoantibody that predicts obstetrical
APAS: lupus anticoagulant
• Maternal and Fetal Infections
o Rubella and CMV
▪ Both promote calcifications in the fetus
associated with cell death
o Tuberculosis and syphilis
o Toxoplasma gondii → congenital infection →
FGR
o Congenital malaria
• Congenital Malformations
o The more severe the malformation, the more
likely it is that the fetus will be SGA
• Chromosomal Aneuploidies
o Fetuses with autosomal Trisomies display poor
fetal growth
o Trisomy 21 → FGR generally mild
o Trisomy 18 → growth is significantly limited
o Turner syndrome → poor FG
o Confined Placental Mosaicism (CPM): patches in
the placenta; recognized cause of FGR
FETAL GROWTH RESTRICTION RECOGNITION
• Prior growth restricted fetus → increased recurrence to
nearly 20%
• Second trimester sonography is superior to first trimester
scans for predicting SGA neonates
• Sonography → most common method for identifying poor
fetal growth
Amnionic Fluid Volume Measurement
• Association between pathological fetal-growth restriction
and oligohydramnios has long been recognized
Doppler Velocimetry
• Umbilical artery Doppler velocimetry improves clinical
outcomes
• Recommended in the management of fetal growth
restriction as an adjunct to standard surveillance
techniques
FGR Management
• Antenatal corticosteroids for pulmonary maturation be
given to pregnancies complicated by fetal growth
restriction and at risk for birth before 34 weeks AOG
Management of a Near Term Fetus
• If with normal doppler velocimetry, normal AF, and
reassuring FHR → can be delayed until 38 weeks AOG
FETAL OVERGROWTH
• Macrosomia – BW >90th percentile for age
• Or weighs >4500g
Risk Factors:
Obesity
Very large baby in previous pregnancy
Exceeding 42 weeks (post term)
Racial and ethnic factors
Gurang (AMA)
Recently in twin gestations
Obviously diabetes
With large sized parents
Management:
• ACOG does not support a policy for early labor induction
or delivery before 39 weeks AOG
• Elective CS: on the basis of suspected macrosomia to
prevent brachial plexopathy
107

CHAPTER 45
Multifetal Pregnancy
• Results from 2 or more fertilization events
• From a single fertilization followed by an “erroneous”
splitting of the zygote
• Increased risk for both mother and child
– 60% of twins, 90% of triplets and 100% of
quadruplets deliver prematurely
• Rates have dramatically increased since 1980
MECHANISMS OF MULTIFETAL GESTATION
• Usually result from fertilization of two separate ova –
dizygotic or fraternal twins
• Less often: from a single fertilized ovum that divides –
monozygotic or identical twins
• Genesis of monozygotic twins
– Poorly understood
– Minor trauma to the blastocyst during assisted
reproductive technology
– Outcome depends on when division occurred
• Risk factors
– Use of fertility stimulating drugs
– Maternal age >37 years old
– Race
– Parity – increasing parity = increased chance of
twinning
– Family history of twinning
– Maternal weight and height
• Factors that influence twinning
– Race: highest in African America, lower in
American
– Maternal age: dizygotic twinning frequency
increases almost fourfold between 15-37 years
– Parity: increasing parity = increasing incidence
– Heredity
– Nutritional Factors
– Pituitary Gonadotropin
– Infertility therapy: ovulation induction with FSH
+ chronic gonadotropins or clomiphene citrate
• Greater the number of embryos that
are transferred = greater risk of
multiple gestation
COMPLICATIONS OF MULTIFETAL PREGNANCY
• Complications of multifetal pregnancy
– Preterm labor
– Preeclampsia
– Gestational diabetes
– Acute fatty liver
– Venous thromboembolism
– Anemia
– Polyhydramnios
– Malpresentation
– Hyperemesis gravidarum
– Abnormal placentation
SUPERFETATION AND SUPERFECUNDATION
• Superfetation: an interval as long as or longer than a
menstrual cycle intervenes between fertilizations
– Not yet known to occur spontaneously in
humans
• Superfecundation: fertilization of two ova within the same
menstrual cycle but not at the same coitus
• Frequency of twinning
– Dizygotic is more common than monozygous
splitting of a single oocyte
• The vanishing twin:
– Scans from the second trimester reveal only 1
fetus (10-40% of all pregnancies)
• Monochorionic twins have a greater risk of abortion than
dichorionic twins
DETERMINATION OF ZYGOSITY
• Twins of opposite sex are almost always dizygotic
• Most are due to the loss of the post zygotic Y chromosome
• Chorionicity can sometimes be identified in the 1st
trimester
• 2 separate placentas → dizygosity
• Sonological determinants
• Twin peak sign: Dichorionicity
– Seen by examining the point of origin of the
dividing membrane on the placental surface
– Peak appears as a triangular projection of
placental tissue extending a short distance
between the layers of the dividing membrane
• T sign: monochorionic
– Have a dividing membrane that is so thin
– Membrane is <2mm thick and magnification
reveals only 2 layers
MATERNAL ADAPTATIONS TO MULTIFETAL PREGNANCY
• Severe hyperemesis gravidarum (higher than the usual
beta Hcg)
• Blood volume expansion 50-60% (singleton: 40-50%)
• Hypervolemia, decreased vascular resistance
• Uterine growth achieves a total of 10L
PREGNANCY COMPLICATIONS
• Spontaneous Abortion
• Congenital Malformations
• Low birthweight
– Degree of growth restriction increases with fetal
number
– Greater growth restriction in monozygotic vs
dizygotic twins
• Hypertension
– Increased for triplets and quadruplets vs twins
– Fetal number and placental mass
– High level of sFlt-1
108
 • Preterm Birth
– Duration of gestation decreases with increasing
fetal number
– Increased neonatal morbidity
– Increased sixfold (twins) and tenfold (triplets)
• Prolonged pregnancy
– Beyond 39 weeks increases the risk of still birth
• Long term infant development
– Cerebral palsy risk is higher among multifetal
gestation
– Monoamnionic Twins
– Only 1% of all monozygotic twins will share an
amnionic sac
– High fetal death rate from cord entanglement,
congenital anomalies, preterm birth or twin-
twin-transfusion syndrome
ABERRANT TWINNING MECHANISMS
• Conjoined Twins
– Aka Siamese twins
– Thoracopagus is the most common
– Surgery may be successful if essential organs are
not shared
• External Parasitic Twins
– Grossly defective fetus or merely fetal parts
attached externally to a relatively normal twin
– From demise of the defective twin with its
surviving tissues attached to and vascularized by
the normal twin
– Joining of the twins may begin at either pole and
may produce characteristic forms depending on
which body part are joined or shared
• Fetus in fetu
– One embryo enfolded within its twin
– Normal development arrests in the first
trimester
– Vertebral or axial bones are present, whereas
heart and brain are lacking
MONOCHORIONIC TWINS AND VASCULAR ANASTOMOSES
• Artery-to-artery anastomoses are most common and are
identified on the chorionic surface of the placenta in 75%
of monochorionic twin placentas
• Deep arteriovenous anastomoses create a common villous
compartment or third circulation
• Whether it is dangerous depends on the degree to which
they are hemodynamically balanced
TWIN TO TWIN TRANSFUSION SYNDROME
• Blood is transfused from a donor twin to its recipient
sibling
• Donor might eventually be anemic, and growth could be
restricted
• Recipient becomes polycythemia and may develop
circulatory overload (could manifest as hydrops)
• Donor twin is pale, recipient sibling is plethoric
• Results from unidirectional flow through arteriovenous
anastomoses
• Deoxygenated blood from a donor placental artery is
pumped into a cotyledon shared by the recipient
• Once oxygen exchange is completed in the chorionic villus,
the oxygenated blood leaves the cotyledon via a placental
vein of the recipient twin
• Results from significant vascular volume differences
between the twins
• Presents in mid pregnancy (donor fetus becomes oliguric
from decreased renal perfusion
• Fetal brain damage
– Cerebral palsy, microcephaly, porencephaly and
multicystic encephalomalacia
– Exact pathogenesis is not fully understood
– May likely be caused by ischemic necrosis
– Donor twin: ischemia from hypotension, anemia
or both
– Recipient twin: ischemia from BP instability and
episodes of severe hypotension
• Diagnosis:
– Based on 2 criteria:
• Presence of monochorionic diamnionic
pregnancy
• Hydramnios (defined if the largest
vertical pocket >8cm in one twin and
oligohydramnios if the largest vertical
pocket is <2cm in the other twin)
– Quintero Staging System
QUINTERO STAGING SYSTEM
Stage I Discordant AFV but urine is still visible
sonographically within the bladder of the donor
twin
Stage II Stage I + urine is not visible
Stage III Stage II + abnormal doppler studies of the
umbilical artery, ductus venosus or umbilical vein
Stage IV Ascites or frank hydrops in either twin
Stage V Demise of either fetus
MANAGEMENT AND PROGNOSIS
• Related to Quintero stage and gestational age at
presentation
• More than 75% of stage I cases remain stable or regress
without intervention
• Sate III or higher: perinatal loss rate is 70-100%
• Amnioreduction
• Laser ablation of vascular anastomoses
TWIN ANEMIA POLYCYTHEMIA SEQUENCE (TAPS)
• Significant hemoglobin differences between donor and
recipient twins WITHOUT discrepancies in amnionic fluid
volumes
• Diagnosed antenatally by MCA peak systolic velocity >1.5
multiples of the median (MoM) in the donor and <1.0
MoM in the recipient twin
• Spontaneous TAPS occur after 26 weeks
• Iatrogenic TAPS develop within 5 weeks of a procedure
• No staging system yet
TWIN REVERSED ARTERIAL PERFUSION (TRAP)
• AKA Acardiac twin
• There is usually a normally formed donor twin that has
features of heart failure and a recipient twin that lacks a
heart and other structures
• Caused by a large artery-to-artery placental shunt
• Arterial perfusion pressure of the donor twin exceeds that
in the recipient twin who thus receives reverse blood flow
of deoxygenated arterial blood from its cotwin
109
• The used arterial blood reaches the recipient twin through
its umbilical arteries and it goes to its iliac vessels → only
lower body is perfused and disrupted growth and
development of the upper body results
• Trap sequence
– Failure of head growth – acardius acephalus
– Partially developed head with identifiable limbs
– acardius myelacephalus
– Failure of any structure to form acardius
amorphous
• Treatment:
– 90% survival rate following second trimester
radiofrequency ablation
TWIN MOLAR PREGNANCY
• Complete H.mole with coexisting normal fetus
• Due to a complete diploid molar pregnancy compromising
one conceptus whereas the cotwin is a normal fetus
• 1 in 22,000 to 1 in 100,000 pregnancies
• Optimal management is not known for this twin gestation
• Diagnosis: first half of pregnancy and termination would
not only remove the mole but also the normal fetus
• Pregnancy progression exposes the woman to later
postpartum dangers of persistent trophoblastic disease
• Preterm delivery is frequently required because of
persistent and heavy bleeding or severe preeclampsia
DISCORDANT GROWTH OF TWIN FETUSES
• Size inequality of twin fetuses is calculated using the larger
twin as the index
• Develops in approximately 15% of twin gestations
• Indicates higher risk for fetal demise in the smaller twin
• If before 20 weeks, fetal death occurs in 20%
• Etiology is unclear
– Discordancy in monochorionic twins → placental
vascular anastomoses → hemodynamic
imbalance between the twins
– Discordancy in dichorionic twins – placentas are
separate and require more implantation space,
one placenta might have suboptimal
implantation site
FETAL DEMISE
• When this occurs early in pregnancy it may manifest as
vanishing twin
• Fetal death in a slightly more advanced gestation may go
undetected until delivery
– Fetus compressus: compressed, barely
identifiable
– Fetus papyraceus: flattened
• Other factors affecting prognosis of surviving twin:
– Gestational age at time of demise
– Duration between demise and delivery
• The odds of spontaneous and iatrogenic preterm delivery
of the remaining living twin were increased
• Preterm birth 5x more likely in monochorionic twin
gestations complicated by demise of one twin between 28-
33 weeks AOG
• If fetus died after 34 weeks, preterm delivery rates are
similar
• Death of one of multiple fetuses could theoretically trigger
coagulation defects in the mother
MANAGEMENT OF TWIN DEATH
• If loss occurs after the first trimester the risk of death or
damage to the survivor is largely limited to monochorionic
twin gestations
• Single fetal death during the late second and early third
trimester presents the greatest risk to the surviving twin
PRENATAL CARE AND ANTEPARTUM MANAGEMENT
• Seen every 2 weeks beginning at 22 weeks
• Assessment of fetal growth and AFV every 4 weeks in
monochorionic and every 6 weeks in dichorionic
• Diet:
– 37-45 lb. weight gain for women with normal
BMI
– Increase caloric intake to 40-45kcal/kg/day
• 20% protein
• 40% carbohydrate
• 40% fat
• Surveillance of fetal growth and health
• Serial sonographic examinations throughout the third
trimester
– Quantifying AFI
– AFI highest at 26-28 weeks AOG and declined
until delivery
– SVP <2cm: oligohydramnios, >8cm hydramnios
TESTS OF FETAL WELL BEING
• BPS
• NST
• Umbilical artery doppler velocimetry
• Pulmonary maturation
• Amniocentesis between 36-38 weeks to determine
pulmonary maturity
– In complicated cases, it may be performed
earlier
PRETERM BIRTH
• Common and may complicated up to 50% of twin, 75% of
triplet and 90% of quadruplet pregnancies
• Prediction:
– At 24 weeks: cervical length <25mm – best
predictor of birth before 32 weeks
– At 28 weeks: elevated fetal fibronectin
• Prevention of preterm birth
– Bed rest: Limited activity, early work leave, more
frequent health care visits and sonographic
examinations and structured maternal education
should be advocated
– Prophylactic tocolysis
– Vaginal progesterone
– Cerclage: not been shown to improve perinatal
outcome
– Pessary:
• Encircles and theoretically compresses
the cervix, alters the inclination of the
110
 cervical canal and relieves direct
pressure on the internal cervical os
• Most popular: Arabin pessary
• Performed between 12-20 weeks
TREATMENT OF PRETERM BIRTH:
• Glucocorticoids for lung maturation
• Assess for expectant management
• Preterm premature membrane rupture
– Expectant
– There must be careful evaluation for infection,
abruption and congenital anomalies
– Mother must be thoroughly counseled regarding
potential for serious, life-threatening infection
– Avoidance of delivery from 23-26 weeks would
seem most beneficial
LABOR AND DELIVERY
• A trained attendant should remain with the mother
• IVF: PLRS or D5NR at 60-125cc.hr
• Blood transfusion ready
• Readily available ultrasound
• Anesthesiologist available
• Evaluation upon admission
• Fetal presentation:
– Cephalic cephalic
• Trial of labor
• May deliver spontaneously or with
forceps
– Cephalic breech
• CS preferred
– Cephalic transverse
• CS preferred
• and appendectomy
BREECH PRESENTATION OF FIRST TWIN
• Major problems may develop if:
– Fetus is unusually large and the aftercoming
head is larger than the birth canal
– Fetal body is small and delivery of extremities
and trunk through an inadequately effaced and
dilated cervix causes the relatively larger head to
become trapped
– Umbilical cord prolapse
• Locked Twins:
– As the breech of the first twin descends through
the birth canal, the chin locks between the neck
and chin of the second cephalic presenting
cotwin
• Internal podalic version
– The fetus is turned into a breech presentation
using the hand placed into the uterus
– Grasp the fetal feet foot then effect delivery by
breech extraction
• Selective reduction
– Reduction of a selected fetus or fetuses in a
multichorionic multifetal gestation
– To enhance survival of the remaining fetuses
– Transabdominal route is preferred
– Performed between 10-13 weeks
– The smallest fetus or any fetus with anomaly is
chosen for reduction
– KCl is injected into the heart or thorax of each
selected fetus
• Selective termination
– Anomalies are typically not discovered until the
second trimester, selective termination is
performed later in gestation
• Not performed unless the anomaly is severe but not lethal
• Prerequisites to selective termination:
– Precise diagnosis of the anomalous fetus
– Absolute certainty of fetal location
CHAPTER 46
General Considerations and Maternal
Evaluation
PERINATAL MORBIDITY:
• Excessive perinatal morbidity associated with
nonobstetrical surgery is attributable in many cases to the
disease itself rather than to adverse effects of surgery and
anesthesia
LAPAROSCOPIC SURGERY
• MOST COMMON first trimester procedure used for
diagnosis and management of several surgical disorders
• Frequently performed – cholecystectomy, adnexal surgery
• Hemodynamic Effects:
o Increased respiratory rate
o Respiratory acidosis
o Diminished CO
o Increased pulmonary artery and capillary wedge
pressures
IONIZING RADIATION:
• Biological effects of x-rays are caused by an
electrochemical reaction that can damage tissue
• 2 types of biological effects:
o Deterministic effects: congenital malformations,
fetal growth restriction, MR, abortion
▪ Threshold for gross fetal
malformations: 0.2Gy (20rad)
o Stochastic effects: random, presumably
unpredictable oncogenic or mutagenic effects of
radiation exposure
▪ Increased risk of childhood cancers or
genetic diseases
• From 8-15 weeks, the fetus is most susceptible to radiation
induced mental retardation
o Risk: 4% for 0.1Gy (10 rad)
o As high as 60% for 1.5Gy (150rad)
• Xray dosimetry: the farthest from the uterus result in a
very small dose of radiation scatter to the embryo or fetus
• AP view chest radiograph is the most commonly used
study and fetal exposure is exceptionally small – 0.0007 Gy
or 0.07mrad
111
 • Computed Tomography: most commonly performed study
in gravidas
o Usually for brain CT → radiation dose is
negligible
• Radiographic Contrast Agents
o Intravenous contrast agents are category B
• MRI: does not use ionizing radiation
o Advantages: high soft tissue contrast, ability to
characterize tissue and acquisition of images in
any plane
o Safety: no harmful human effects, can be used
regardless of trimester
▪ If information cannot be obtained with
another non-ionizing modality
▪ If results will guide management
▪ Imaging cannot be delayed
o Contraindications: internal cardiac pacemakers,
neurostimulators, implanted defibrillators and
infusion pumps, cochlear implants, shrapnel or
other metal, some intracranial aneurysm clips or
any metallic foreign body
GUIDELINES FOR DIAGNOSTIC IMAGING DURING PREGNANCY AND
LACTATION
• Sonography and MRI are not associated with fetal risk and are
preferred options for imaging
• Radiation exposure during radiography, CT or nuclear medicine
imaging delivers a dose much lower than that associated with
fetal harm
• With MR imaging – gadolinium is restricted (unless absolutely
necessary)
• Breastfeeding should not be interrupted after gadolinium
administration
CHAPTER 47
Critical Care and Trauma
ACUTE PULMONARY EDEMA
2 GENERAL CAUSES:
• Cardiogenic: hydrostatic edema caused by high pulmonary
capillary hydraulic pressure
• Noncardiogenic: permeability edema caused by capillary
endothelial and alveolar epithelial damage
o Mostly seen in pregnancy
Noncardiogenic Permeability Edema
• Endothelial activation is the common denominator that is
associated with preeclampsia, sepsis syndrome and acute
hemorrhage → Most common predisposing factors to
pulmonary edema
Management:
• Furosemide given in 20-40mg IV doses along with therapy
to control severe hypertension
ACUTE RESPIRATORY DISTRESS SYNDROME
• Radiographically documented pulmonary infiltrates
• A ratio of arterial oxygen tension to the fraction of inspired
oxygen <200
• No evidence of heart failure
Etiopathogenesis:
• More than half of women with ARDS have some
combination of sepsis, hemorrhage, shock and fluid
overload
• Endothelial injury in the lung capillaries → cytokines →
recruit neutrophils to the inflammation
• 3 stages of ARDS:
o Exudative phase: widespread injury to
microvascular endothelium including the
pulmonary vasculature + alveolar epithelial
injury → increased pulmonary capillary
permeability → loss of surfactant or inactivation
→ diminished lung volume and vascular shunting
→ arterial hypoxemia
o Fibroproliferative phase: begins 3-4 days later
and lasts up to 21 days
o Fibrotic phase: from healing and despite this, the
long term prognosis for pulmonary function is
good
Clinical Course:
• Important to recognize and treat underlying medical and
surgical disorders
• Minimizing procedures and their complications
• Administering prophylaxis against venous
thromboembolism, GI bleeding, aspiration and central
venous catheter infection
• Promptly diagnosing nosocomial infections
• Providing adequate nutrition
• Each gram of hgb carries 1.25mL of oxygen when 90%
saturated
• Goal: attain a PaO2 of 60mmHg or 90% O2 saturation
using inspired oxygen content
Fetal oxygenation:
• To achieve 50% hgb saturation, the PaO2 must be
27mmHg in the mother compared with only 19mmHg in
the fetus
IV fluids
• Conservative rather than liberal
• Some pregnancy induced physiological changes predispose
to a greater risk of permeability edema
• Colloid oncotic pressure is determined by serum albumin
concentration and 1g/dL exerts approximately 6mmHg
pressure
• Serum albumin concentrations normally drop in pregnancy
→ decline in oncotic pressure from 28mmHg to 23mmHg
at term and 17mmHg puerperium
SEPSIS SYNDROME
• Induced by a systemic inflammatory response to bacteria,
viruses or their byproducts such as endotoxins and
exotoxins
• Infections that most commonly cause sepsis syndrome in
pregnancy is pyelonephritis, chorioamnionitis, puerperal
sepsis, septic abortion, necrotizing fasciitis
Etiopathogenesis:
• Comes from lipopolysaccharide 0 LPS or endotoxin
112
 • Clinical aspects of the sepsis syndrome are manifested o Blocks hepatic glucose release
when cytokines are release that have endocrine, paracrine o Cardioprotective effects on circulating plasma
and autocrine actions lipids
• Bacteria that cause severe sepsis syndrome are frequently o Deficit in adiponectin: linked with diabetes,
endotoxin producing Enterobacteriaceae (E. coli) hypertension, endothelial cell activation and CV
• CA-MRSA produces a superantigen that activates T cells → disease
rapidly cause all features of the sepsis syndrome • Cytokines that result in insulin resistance are: leptin,
• Begins with an inflammatory response directed against resistin, TNF-alpha and IL-6
microbial endotoxins and exotoxins → CD4 T cells and • Adipokines (esp inflammatory cytokines) may be the
leukocytes are stimulated to produce proinflammatory primary stimulant of insulin resistance
compounds (TNF-alpha, several IL) → cytokine storm • In gestational diabetes: low adiponectin, high leptin
• Selective vasodilation with maldistribution of blood flow
→ leukocyte and platelet aggregation cause capillary METABOLIC SYNDROME
plugging → endothelial injury worsens → profound • Obesity interacts with inherited factors to cause insulin
permeability → capillary leakage and interstitial fluid resistance
accumulation → septic shock • Characterized by impaired glucose metabolism and a
Clinical Manifestations: predisposition to type 2 diabetes
• Warm phase: pulmonary hypertension develops and • Preferred measurement for screening: waist
despite high cardiac output → severe sepsis causes circumference
myocardial depression NON-ALCOHOLIC FATTY LIVER DISEASE
• Cold phase: oliguria and continued peripheral • Excessive fat accumulates in the liver → hepatic steatosis
vasoconstriction AKA NAFLD
Management: • In persons with metabolic syndrome, steatosis can
• Cornerstone: EARLY GOAL DIRECTED MANAGEMENT progress to nonalcoholic steatohepatitis (NASH), cirrhosis
• Most important step in sepsis management: rapid infusion and carcinoma
of 2L and sometimes 4-6L of crystalloid fluids to restore OBESITY ASSOCIATED MORBIDITY
renal perfusion • Obese individuals suffer well known consequences such as
glucose intolerance, hypertension, dyslipidemia and
TRAUMA metabolic syndrome
PREGNANCY AND OBESITY
Trauma Features • Obesity and metabolic syndrome are characterized by
Physical Abuse • Tends to present late in pregnancy insulin resistance → low grade inflammation →
• Uterine rupture, preterm delivery and endothelial activation → play a role in eclampsia
maternal and perinatal death • NAFLD is associated with risks for preeclampsia, preterm
• Screen patients during each trimester birth, low birthweight, CS, GDM
Sexual assault • CDC recommends antimicrobial prophylaxis • Perinatal Mortality: stillbirths are more prevalent as the
against gonorrhea, chlamydia, BV and degree of obesity accrues
trichomoniasis o High maternal BMI in early pregnancy is a risk
Automobile • Motor vehicle crashes are the most common factor
accidents causes of serious, life-threatening or fatal o Greater incidence for macrosomic newborns
blunt trauma during pregnancy • Antepartum Management
• Half due to not wearing seatbelt o Overweight women: weight gain of 15-25 lbs. is
suggested
Fetal injury and • More likely with direct fetoplacental injury,
o Obese women: 11-20 lbs.
death maternal shock, pelvic fracture , hypoxia
• Restrictive Malabsorptive Procedures
o The laparoscopically performed Roux-en Y
CHAPTER 48 gastric bypass is the most commonly used
procedure for gastric restriction and selective
malabsorption
Obesity o ACOG recommends that women who have
BMI INTERPRETATION undergone bariatric surgery be assessed for
18.5-24.9 Normal vitamin and nutritional sufficiency
25-29.9 Overweight ▪ Vitamins B12, D, folic acid and calcium
>30 Obese are given
30-34.9 Class 1
35-39.9 Class 2
>40 Class 3 – morbidly obese
>50 Super morbid obesity

ADIPOSE PATHOPHYSIOLOGY
• Principal adipokine – adiponectin (30-kDa protein)
o Enhances insulin sensitivity
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 CHAPTER 49
• Echocardiography: permits accurate diagnosis of most heart diseases during
Cardiovascular Disorders pregnancy
PHYSIOLOGICAL CONSIDERATIONS IN PREGNANCY
• Cardiovascular MR imaging: can assess right ventricle
Cardiovascular Physiology
• Marked pregnancy-induced anatomical and functional changes in cardiac
CLASSIFICATION OF FUNCTIONAL HEART DISEASES:
physiology can have a profound effect on underlying heart disease
• Class I: uncompromised – no limitation
• Cardiac output increases 40%
• Class II: slight limitation of physical activity – comfortable at rest but if ordinary
• Almost half of this total takes place by 8 weeks gestation and is maximal
physical activity → discomfort, fatigue, palpitations, dyspnea or angina
midpregnancy
• Class III: marked limitation – comfortable at rest but less than ordinary activity
• Later in pregnancy: resting pulse and SV are even higher due to greater end-
causes excessive fatigue, palpitation, dyspnea and angina
diastolic ventricular volume
• Class IV: severely compromised - inability to perform any physical activity without
Ventricular Function in Pregnancy
discomfort
• Ventricular volumes and mass accrue to accommodate pregnancy-induced
hypervolemia → reflected by greater end-systolic and end-diastolic dimensions
WHO RISK CLASSIFICATION OF CVD AND PREGNANCY WITH MANAGEMENT
• Septal thickness and EF unchanged
• Plasticity: eccentric expansion of left ventricular mass that averages 30-35% near Risk Category Associated Conditions Cardio Follow-up
term WHO 1 – risk no • Uncomplicated, small or mild: Once or twice
• Ventricular function during pregnancy is normal higher than general • Pulmonary stenosis, VSD, PDA, mitral valve prolapse during pregnancy
• Longitudinal remodeling: left ventricle undergoes remodeling in nonpregnant population • Successfully repaired simple lesions: ostium secundum
patients with a normal heart who sustain a high output state ASD, VSD, PDA
• Spherical remodeling: in pregnancy • Isolated ventricular extrasystoles and atrial ectopic beats
• Cardiac MRI: used to evaluate cardiac structure and function WHO 2 – small If otherwise uncomplicated: Each trimester
increase in risk of • Unoperated ASD
maternal mortality • Repaired fallot
DIAGNOSIS OF HEART DISEASE
and morbidity • Most arrythmias
• ECG: normally: reduced PR interval, inverted or flattened T waves and a Qwave
WHO 2 or 3 – • Mild left ventricular impairment Individualized
• Clinical Indicators of Heart Disease During Pregnancy: depends on • Hypertrophic cardiomyopathy care
o Symptoms: individual case • Native or tissue valvular heart disease not considered
▪ Progressive dyspnea or orthopnea WHO 4
▪ Nocturnal cough • Marfan syndrome without aortic dilation
▪ Hemoptysis • Heart transplant
▪ Syncope WHO 3 – • Mechanical valve Care directed by
▪ Chest pain significantly • Systemic right ventricle multispecialty
o Clinical Findings: increased risk of • Post fontan operation team monthly,
▪ Cyanosis mortality or expert • Cyanotic heart disease bimonthly
cardiac and • Other complex congenital heart disease
▪ Clubbing of fingers obstetric care
▪ Persistent neck vein distention required
▪ Systolic murmur grade 3/6 or greater WHO 4 – very high • Pulmonary arterial hypertension If pregnancy
▪ Diastolic murmur risk of mortality • Severe systemic ventricular dysfunction occurs: monthly
▪ Cardiomegaly Pregnancy is • Previous peripartum cardiomyopathy with residual or bimonthly
▪ Persistent tachycardia and/or arrhythmia contraindicated impairment of left ventricular function
▪ Persistent split second sound • Severe left heart obstruction
▪ Fourth heart sound • Marfan with aorta dilated >40mm
▪ Criteria for pulmonary hypertension

114
LABOR AND DELIVERY
• Vaginal delivery is preferred
• Labor induction usually safe
• CS for obstetrical indications or for:
o Dilated aortic root >4cm or aortic aneurysm
o Acute severe congestive heart failure
o Recent myocardial infarction
o Severe symptomatic aortic stenosis
o Warfarin administration within 2 weeks of delivery
o Need for emergency valve replacement immediately after delivery

ANALGESIA AND ANESTHESIA:

• Relief from pain and apprehension is important
• Major problem is maternal hypotension
• Epidural anesthesia preferred

INTRAPARTUM HEART FAILURE

• CV decompensation during labor may manifest as: pulmonary edema with hypoxia
or as hypotension
PUERPERIUM
• Postpartum hemorrhage, anemia, infection and thromboembolism are much more
serious complications with heart disease

115
SURGICALLY CORRECTED HEART DISEASES
Anticoagulation Pregnancy after heart transplantation
Critical for women with mechanical prosthetic valves In stable heart transplant patients, pregnancy is not discouraged more than 1 year
Warfarin is the most effective anticoagulant for preventing mat thromboembolism but causes harmful posttransplant
fetal effects
Heparin is given instead of warfarin
• Stopped before surgery
• Resumed 6 hrs following vaginal delivery
• If CS = full anticoagulation is withheld
o ACOG advises: resume heparin 6-12 hours after CS

VALVULAR HEART DISEASES

TYPE CAUSE PATHOPHYSIOLOGY PREGNANCY
Mitral stenosis Rheumatic valvulitis LA dilation and passive pulmonary hypertension; atrial Heart failure from fluid overload,
fibrial fibrillation tachycardia
Mitral insufficiency Rheumatic valvulitis, mitral valve LV dilation and eccentric hypertrophy Ventricular function improves with
prolapse, LV dilation afterload decrease

Aortic stenosis Congenital bicuspid valve LV concentric hypertrophy, decreased cardiac output Moderate stenosis is tolerated; severe is
life-threatening with decreased preload

Aortic insufficiency Rheumatic valvulitis, connective tissue LV hypertrophy and dilation Ventricular function improves with
disease afterload decrease

Pulmonary stenosis Rheumatic valvulitis Severe stenosis associated with RA and RV enlargement Mild stenosis usually well tolerated;
severe stenosis associated with right
heart failure and atrial arrhythmias

116
RESPIRATORY COMPLICATIONS
DISEASE DEFINITIONS AND ETIOLOGY AND DIAGNOSIS COMPLICATIONS PREGNANCY TREATMENT
BURDEN OF PATHOPHYSIO CONSIDERATIONS
DISEASE
ASTHMA 3-8% of pregnant • Airway • Wheezing, shortness of breath, chest tightness, • Pregnancy has Pre-conception Intermittent Asthma:
women obstruction difficulty in breathing unpredictable effect • Eliminate or mitigate • SABA PRN
0.9% of total OB and • Variable expiratory airflow obstruction before and on asthma (rule of asthma triggers Mild Persistent
admissions (36% inflammation after bronchodilator inhalation or before and after thirds) • Multidisciplinary care • Low dose ICS
due to acute due to intitiation of empiric treatment for asthma • Exacerbations are • Education on • Medium dose ICS
exacerbations) excessive • Spirometry: FEV1 >12% improvement more common with prognosis, • Cromolyn
response to CLASSIFICATION: severe asthma complications and • Montelukast
stimuli → Compo- Intermi Persistent • Small increased risks management during Moderate Persistent
bronchial nent -ttent Mild Mod Sev of PES, PTL, LBW pregnancy • Medium dose ICS +
edema → Sx <2d/w >2d/w Daily All day • If controlled → no Prenatal Care LABA or montelukast
airway significant increase in • Objective monitoring Severe Persistent
Noctur <2x/mo 3-4x /m >1/w 7x
remodeling adverse perinatal of maternal lung fx and • High dose ICS + LABA
nal outcomes fetal well-being or montelukast + oral
SABA <2/w >2d/w Daily Several • Possible teratogenic or • Control of systemic
but not adverse fetal effects of environmental corticosteroids
>1x/d drugs (corticosteroids factors/triggers
ADL Normal Minor Some Limited → cleft palate) • Patient education At home/immediate
• Pharma relief of Acute Exacerb
Peripartum Care • SABA
• Asthma meds • Persistence of
• Oxy, PGE1 or PGE2 wheezing + SOB →
• PGF2a and ergot SABA + oral
contraindicated corticosteroids
• Regional anes • Marked wheezing /
• Continuous CTG SOB even after tx →
Postpartum ER
• Asthma meds not CI • Monitor fetal kick
for BF count
• NSAIDs

117
 DISEASE DEFINITIONS AND ETIOLOGY AND DIAGNOSIS COMPLICATIONS PREGNANCY TREATMENT
BUR OF DIS PATHOPHYSIO CONSIDERATIONS
PNEUMONIA Infectious • Bacterial (strep) • Sx: cough, • Pregnancy does • Prophylactic • Bacterial: antibiotics
process of lower • Viral (Influenza dyspnea, not predispose to administration • Admit for 24 hrs → close maternal-fetal monitoring and initial
respiratory tract A and B, sputum pneumonia of ACS for fetal treatment with hydration, antipyretics, supplemental O2 if indicated
CAP is more varicella-zoster) production, • Incidence is lung maturity in • Diagnostic tests: CXR with ab shield, CBC, electrolytes, serum BUN, ABG,
common during • Fungal: pleuritic evenly distributed pregnant sputum GSCS, blood culture
pregnancy uncommon chest pain, throughout women with • Empiric antibiotics: as soon as diagnosis is likely or confirmed by CXR
Risk factors for • Causative agent fever pregnancy CAP who are even without microbiologic evidence
CAP in women is identified in • PE: temp • Risk of intubation not in labor → • Outpatient management is option as long as with stable VS or with
with RTI: only 40-60% of >37.8, 2-7% not stable comorbids
-preexisting the cases HR>100, • Risk of maternal recommended LOW-RISK – 5 DAYS TX
chronic maternal (microbiology) RR>20, mortality 1-2% • Elective delivery Without co-morbids
disease crackles, • Higher rates of with respiratory • Amox 1g TID or extended macrolides Azith 500mg OD or clarithromycin
-smoking decreased PTB, abruptio failure → no 500mg BID
-use of ACS and breath evidence that With comorbids
tocolytics sounds, delivery will • Beta lactam/lactamase inhibitor combination (BLIC) or 2nd gen oral
absence of improve their cephalosporin +/- macrolides
asthma respiratory o Coamox 1g BID
• Chest xray: status (only for o Sultamicillin 750mg BID
gold OB indications) o Cefu 500mg BID +/-
standard to • Induction of o Azith 500mg BID
confirm the labor → does o Clarith 500mg BID
diagnosis not improve, MOD RISK
(0.001 rads will not respond • IV non-antipseudomonal beta lactam + extended macrolides + respi
→ well fluoroquinoles (levofloxacin)
threshold • No specific HIGH RISK
20-40rads) changes in • IV antipseudomonal B lactam + IV xtended macrolides or respi
• Microbiolog antepartum, fluoroquinoles (ceftri 2g OD or ertap 1g OD + azith 500 OD IV or levoflox
ical studies: delivery, 500mg OD IV or moxifloxacin 400mg OD IV
only for anesthesia and • STEP DOWN TO ORAL if afebrile for at least 48-72 hrs and clinically
moderate postpartum stable
to severe care INFLUENZA A AND B PNEUMONIA (CAT C)
CAP (yield • Oseltamivir 75mg/cap, 1 cap BID X 5 d
low results)
• Zanamivir 10mg (2 5mg inhalations) BID X5d
VARICELLA
• Oral acyclovir 800mg 5x a day
• IV Acyclovir 15mg/kg BW Q8 x 5-10d
PNEUMOCYSTIC PNEUMONIA IN HIV INFECTED
• TMP-SMX 2 double strength tabs Q8
• IV TMP-SMX if unable to tolerate oral

118
HEMATOLOGIC COMPLICATIONS
DISEASE DEFINITIONS AND ETIOLOGY AND DIAGNOSIS COMPLICATIONS PREGNANCY TREATMENT
BURDEN OF PATHOPHYSIO CONSIDERATIONS
DISEASE
MATERNAL Global prevalence • Dilutional NORMAL PREGNANCY LEVELS IDA: • Dietary • Iron: 30-
ANEMIA of 25% anemia of • 0-12 weeks: 11 • Increased risk of modification 60mg
Prevalence of pregnancy • 13 to 28 weeks: 10.5 LWB, PTB, • Routine oral elemental
44% in pregnant • Physiologic • 29 weeks to term: 11 perinatal death iron iron + 400ug
women, 42% in anemia • Postpartum: 12 • Severe • Consider fetal folic acid
lactating women occurs a • 2ND trimester – disproportion in red blood cell is greatest in this time maternal biometry in the • Frequency:
result of DIAGNOSIS ACCD TO SEVERITY anemia → 3rd trimester once daily
dilutional • Mild: 9.5-10.5 maternal • During delivery • Duration:
process • Moderate: 8-9.4 cardiovascular → prepare throughout
secondary to • Severe: 6.9-7.9 compromise blood pregnancy
an increase in • Very severe: <6.9 and fetal • IDA: 100-200mg beginning as
plasma CAUSES OF ANEMIA BY MECHANISM cerebral elemental iron, early as
volume • Dilutional (expansion of plasma volume): pregnancy, h yperglobinemia, hypoperfusion repeat hgb after possible
relative to massive splenomegaly 2 (should • Ferrous
red cell • Decreased RBC production: iron def, Vitamin B12 def, folic acid def, BM increase at least fumarate:
volume disorder, low levels of EPO, hypothyroidism 20g/dl) weeks 66mg/200mg
• Increased RBC destruction: inherited – sickle cell; acquired – AHA, TTP, HUS then continue • Ferrous
• Increased loss: hemorrhage, GI bleeding for 3 mos if gluconate:
INITIAL EVALUATION: normal hgb, 36mg/300mg
• CBC, MCV, MCH, MCHC standard • Ferrous
antenatal dose sulfate:
Microcytic Anemia (Hgb <11, MCV <80)
once anemia is 60mg/300mg
• Ferritin (iron storage protein) → low (<15) → IDA ; low normal (15-
40ng/ml) → hgb electrophoresis → hemoglobinopathy; normal or high
corrected • Ferrous
(>40ng/ml) → hgb electrophoresis → dna analysis/pbs → chronic dis / sulfate,
sideroblastic anemia anhydrous
Macrocytic Anemia – obtain B12 and RBC folate level 74mg/200
• Vitamin B12, RBc folate levels: Vitamin B12 <100 → vitamin def → 1mg B12 • Ferrous
iM every week x 8 wks then monthly ; RBC folate <150 → vit def → folic sulfate,
acid 1mg/d in additional to prenatal vitamins exisiccated:
Normocytic Anemia – retic count, ferritin, vita b12, rbc folate (if low → 60mg/200mg
underproduction RDW); if high → hemolysis or blood loss → pbs, coombs, • Iron sucrose:
hgb electrophoresis 20mg/ml IV
• Retic count <3% → RDW normal → infection, medication, renal dis, aplastic • Ferric
anemia; RDW increased → low ferritin, b12, rbc folate → mixed disorder; carboxymalt
RDW increased → normal ferritin, b12, rbc folate → chronic disease 750mg/IV
• Retic count >3% → coombs- → G6pd, hemoglobinopathy, HUS, TTP, SS, SC (1500max)
disease; coombs+ → autoimmune hemolytic anemia

119
HEMATOLOGIC COMPLICATIONS
DISEASE DEFINITIONS AND ETIOLOGY AND PATHOPHYSIO DIAGNOSIS PREGNANCY CONSIDERATIONS
BURDEN OF TREATMENT
DISEASE
Thalassemia Increased • Impaired production of alpha → alpha thal • CBC Preconception:
prevalence in • Instability of beta chains → beta thal • If with microcytic hypochromic • Multidisciplinary team
Africa, ALPHA THALASSEMIA anemia → hgb electrophoresis • Optimize chelation to reduce and optimize body iron burden and reduce end organ
Mediterranean, • 1 globin chain: silent carrier, asx, cbc normal or high performance liquid damage
Middle East, • 2 globin chains: alpha thal minor → asx, cbc mild chromatography (HPLC) • Screen for diabetes
India, China, SE anemia Prompt screening of partner (if Antenatal Care:
asia • 3 globin chains: hgb H dis (alpha thal intermed) → both are carriers for thal → refer • Folic acid supplementation
SEA: alpha chronic hemolytic anemia (mod-sev) → worsens for counselling) • Maintain hgb >10g/dl
thalassemia in pregnancy • Cardio review
prevalence • 4 globin chains: Hgb barts hydrops fetalis, fetal • Antenatal fetal surveillance
demise, total body edema • Antenatal thromboprophylaxis - splenectomy → Low dose aspirin 75mg/day
BETA THAL • Timing of delivery should be individualized
• Major (cooley’s): 2 beta chains, profound • For intermedia with hgb >8g/dl → BT only as needed
microcytic hypochromic anemia, lifelong BT, • For major → give desferrioxamine 2g IV over 24 hrs for the duration of labor, may
splenomegaly, cholelith, hemosiderosis transfuse if hgb <10g/dl
• Intermedia: occasional BT • Active management of 3rd stage of labor
• Minor: mutation in 1 beta chain (Carrier), mild Postpartum:
anemia, Asx • Resume iron chelation with desferrioxamine immediately postpartum, other iron
chelators are CI in breastfeeding
• VTE prophylaxis for 7 days pp after NSD for 6 wks after CS
Thrombocyto- Platelet Pregnancy specific • Personal and family history, • Gestational Thrombocytopenia:
penia <150,000/uL • Gestational thrombocytopenia (75-80%), drugs, dietary habits o Incidental
Occurs in 10% of preeclampsia, HELLP syndrome, acute fatty liver • PE: hematoma, petechia, o Cause is uncertain but may be due to hemodilution, decreased platelet
pregnancies Not pregnancy specific bleeding only if extremely low production or enhanced platelet clearance
• Primary immune thrombocytopenia, secondary • Initial labs: CBC, PBS, coag o Onset mostly mid 2nd or 3rd trimester, ASX, no history, >100,000/uL, low risk
ITP, thrombotic microangiopathies, malignancies, studies, LFT, Anticardiolipin of fetal thrombocytopenia, return to normal 1-2 months postpartum
drugs antibodies, SLE serology o CS not indicated
• Immune thrombocytopenia (AKA Idiopathic Trhombocytopenia)
o Antiplatelet antibodies bind to platelet antigens → premature destruction
of platelets → fetal thrombocytopenia
o Onset mostly 1st to early 2nd trimester
o Spontaneous bleeding if PC <20,000
o Bleeding tendency prior to pregnancy
o <100,000/uL: fetal/neonatal thrombocytopenia possible
o Return to normal possible postpartum
o Complications: increased risk of stillbirth, fetal loss, ptb, intracranial
hemorrhage in the fetus
o Platelet count every trimester
o TX: platelet transfusion <50,000/uL
o Delivery is based on obstetric indications, regional anesthesia

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THYROID DISORDERS
DISEASE ETIOLOGY AND PATHOPHYSIO DIAGNOSIS COMPLICATIONS PREGNANCY TREATMENT
CONSIDERATIONS
Hyper / Hypothyroidism: If symptomatic or if: Hypothyroidsm: Hypothyroidism Subclinical
Hypothyroidism • Primary: • Age >30 • Infertility • TSH, FT4 prior to Hypothyroidism:
o Hashimoto’s – most common • Personal hx of thyroid dysfunction • Miscarriage pregnancy, at first PNCU, • No further
Universal o Iodine deficiency • Prior head/neck radiation • Preeclampsia every 4 weeks until TSH is evaluation or
screening is not o Thyroidectomy, iodine therapy • Prior thyroid surgery • Abruptio normal and at least every treatment needed
recommended or radiotherapy • Family history of thyroid • Preterm birth trimester Overt
o Thyroid agenesis/dysgenesis dysfunction • Low birthweight infants • Prenatal visits: 150-200ug hypothyroidism:
• Secondary: • Goiter • Fetal death iodine • Levothyroxine at 1-
o Pituitary adenoma • TPO and TG antibody+ • Impaired psychomotor function • Antepartum fetal testing: 2mcg/kg/day
o Hypothalamic or suprasellar • Autoimmune disease Hyperthyroidism if clinically hypothyroid • Recheck TSH every
tumors • Infertility • Miscarriage • Measure 6 weeks 4-6 weeks and
o Hypothalamic surgery or • Miscarriage or PTB postpartum titrate to achieve
• Preeclampsia
radiotherapy • Iodine deficient population • Fetal hypothyroidism: due TSH level between
• Abruptio
Sx: to transplacental passage lower rower
• Morbid obesity • PTB
o Weakness, fatigue, constipation, of TPO, transplacental reference limit and
cold intolerance, ms cramps, • CHF
passage of MMI or PTU in 2.5mu/L
• Serum TSH and FT4 are the • Thyroid storm
insomnia, hair loss, voice those with Grave’s Overt
preferred tests to diagnose thyroid • Low bw infant, fetal
changes, dry skin, weight gain, disease, consider if on Hyperthyroidism
disorders thyrotoxicosis, fetal death
goiter, prolonged DTR, UTZ → fetal goiter, • Consider checking
• TSH – single most reliable • Neonatal Grave’s disease
myxedema discontinue MMI, PTU TRAB
indicator of thyroid status (it
directly reflects thyroid levels)
Thyroid Storm: Hyperthyroidism: • PTU 100-160mg in
Hyperthyroidism: • Severe thyrotoxicosis with • Hyperemesis Gravidarum 3 doses OR
o 1st trimester: 0.1-2.5
• Grave’s disease evidence of decompensation – gestational transient methimazole 5-
o 2nd trimester: 0.2-3.0
• Toxic multinodular goiter • Fever, tachycardia, CNS hyperthyroidism due to 30mg in 2 doses →
o 3rd trimester: 0.3-3.0
• Toxic adenoma dysfunction serum hcg: recheck FT4 and T3
• Thyroiditis • TFTs low/undetectable TSH every 2-4 weeks
Elevated TSH → FT4 normal →
• Gestational trophoblastic neoplasia • Inhibit thyroid release of T3 and and/or elevated T4 and titrate to goal
subclinical hypothyroidism; FT4
• Nervousness, tremors, frequent T4 → PTU • Fetal thyrotoxicosis: due of high normal
below normal → overt
stools, sweating, heat intolerance, hypothyroidism • Sodium iodide, lugol solution, to transplacental passage range
insomnia, palpitations, decreased Decreased TSH → FT4, Total T3 lithium of TSI in Grave’s
appetite, eye sx, hypertension, normal → subclinical • Block peripheral conversion of T4 o Consider if with: fetal
tachy, goiter, ophthalmopathy hyperthyroidism; below normal → to T3 → dexa or hydrocortisone goiter, fetal tachy, FGR,
overt hyperthyroidism • Beta blockers hydramnios,
• Fetus will almost always show accelerated bone
NRFHR maturation, heart
failure, hydrops

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GI COMPLICATIONS
DISEASE ETIOLOGY AND PATHOPHYSIO DIAGNOSIS
Hyperemesis Intractable vomiting with signs of Onset: before 9 weeks, peaks
Gravidarum dehydration and weight loss 8-12 weeks, resolves by 20
weeks
Exact etiology unknown Criteria:
Related to high or rapidly rising serum • Intractable vomiting
levels of placental hormones (hCG, >3x/day
estrogen, progesterone, placental GH, • Signs of dehydration
prolactin, thyroxine) • Weight loss of >3kg or >5%
of pre-pregnancy weight
Classification of Severity
• PUQE index (Pregnancy
Unique Quantification of
Emesis)
o Mild: 6
o Moderate: 7-12
o Severe: 13-15
Cholelithiasis Presence of gallstones in the • S/Sx: Recurrent RUQ, pain,
gallbladder bloating, nausea and
Incidence in pregnancy: heartburn
• Biliary sludge: 30% • Labs: blood count, LFT,
• Gallstones in 7% of nulliparous and • Imaging: ultrasound
20% of multiparous
Pathophysio:
Decreased GB motility and increased
lithogenecity of the bile
Acute Inflammation of GB • S/Sx: persistent RUQ pain,
cholecystitis Obstruction of cystic duct anorexia, n/v, inability to
Increased intraluminal pressure → tolerate oral intake
release of tissue factors + bacterial • PE: fever, tachycardia,
invasion murphy’s sign, jaundice,
0.1% of all pregnancies signs of peritonitis
• Labs: blood count, LFT,
amylase, lipase, Alk Phos
• Imaging: ultrasound
COMPLICATIONS PREGNANCY TREATMENT
CONSIDERATIONS
• Acute kidney injury • Early intervention • Lifestyle / dietary changes
• Depression to prevent • Convert prenatal vitamins to folic
• Diaphragmatic rupture worsening acid
• Esophageal rupture • Prenatal vitmains • Ginger 250mg QUID
• Hypoprothrombinemia 3 mos prior to • Vit B6 10-25mg TID or QID
• Hyperalimentation conception • Vit B6/Doxylamine 20mg
complications • Vitamin B6 and combination
• Mallory-Weiss tears doxylamine if • If persistent:
with history of o Dimenhydrinate: H1 receptor
HSG antagonist
• UTZ to rule out o Phenothiazines
molar pregnancy o Assess for dehydration:
or multifetal ondansetron (SSRA) → NOT GIVEN
pregnancy FOR 1ST TRIMESTER
metoclopramide: 5-10mg Q6-8 PO
or IM
• Cholecystitis, cholangitis, • CS for obstetric • Observation for 24 hrs
choledocholitlithaisis, indications • Bowel rest
pacnreatitis or ileus • IV hydration
• No fetal • Opioid analgesics
• Surgery: worsening, inability to
tolerate oral intake, increasing pain,
patient preference
• Sepsis, cholangitis, pancreatitis, • Surgical • Observation (24h)
porcelain gb, increased risk for • Laparoscopic • Bowel rest, IV, opioid
GB cancer • Mode of delivery • Broad spectrum antibiotics
• Fetal: fetal death, delivery, first not affected • Definitive surgical therapy required
trimester miscarriage in pregnant women with sepsis, ileus
or perforation
• Lap chole – treatment of choice
regardless of trimester
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RENAL COMPLICATIONS
DISEASE ETIOLOGY AND PATHOPHYSIO
Asx bacteriuria Persistent, actively. Multiplying
bacteria within the urinary tract in
asymptomatic women
90% due to E. coli
Pregnancy factors: urinary stasis,
vesicoureteral reflux, Th2
predominance, pertuberations of
cytokine / adhesin
Acute cystitis Infection of the bladder or LUT
E. coli – most common organism
isolated
Acute Infection of renal pelvis and kidney
pyelonephritis Results from ascent of a bacterial
pathogen up the ureters form the
bladder to the kidneys
E. coli in 70-80%, gram + organisms
(GBS, S. aureus) in 10%, lebsiella 5%,
enterobacter, proteus 5%
Unilateral (right sided in 50%)
DIAGNOSIS COMPLICATIONS PREGNANCY TREATMENT
CONSIDERATIONS
• More than 100,000 cfu/ml of • Symptomatic infection in • Cefalexin
same pathogen in 2 consecutive 25% if ASB is left • Cefuroxime
midstream speciemsn untreated • Nitrofurantoin
• >100 cfu/ml of a single • TMP-SMX (except during 1st and 3rd
uropathogen in one catheterized trimester)
urine specimen • UCS after 1 week of treatment
• Urine culture – test of choice in
screening
• S/Sx: urinary frequency, urgency, • Cefalexin
dysuria, no fever and • Cefu
costovertebral angle tenderness • Cefaclor
• Dx: UCS • Nitrofurantoin
• In the absence of UCS: >8 pus • Co-amox
cells/mm3 of uncentrifuged urine • TMP-SMX
or >5 pus cells/hpf of centrifuged • Post treatment: urine culture 1-2
urine and a positive leukocyte weeks after completion should be
esterase and nitrite test on obtained
dipstick • Monitor monthly until delivery:
pyelo, recurrent UTI, GMD,
nephrolith, pre-ec
• S/Sx: fever, shaking, chills, flank ADMISSION IF: • Empiric therapy
pain, anorexia, nausea, vomiting, • Inability to maintain oral hydration • IV: ceftriaxone, cefotaxime, ampi-
fever, CV angle tenderness • Concern about compliance sub, reserved: piptazo
• Labs: pyuria >5 wbc/hpf of a • Comorbids • Oral 14 days: cefalexin
centrifuged urine and bacteriuria • Severe illness with high fever, severe pain, • Assess for other urinary tract
with >100,000 cfu/ml on UCS marked debility abnormalities if unresponsive to
• UCS should be performed • Signs of preterm labor meds after 72 hours
• Blood CS only if with signs of • Signs of sepsis • Post treatment UCS
sepsis
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THROMBOEMOBLIC COMPLICATIONS
DISEASE ETIOLOGY AND PATHOPHYSIO DIAGNOSIS COMPLICATIONS PREGNANCY TREATMENT
CONSIDERATIONS
VTE • A condition in which blood clots inappropriately DEEP VEIN THROMBOSIS • DVT: risk of PE, post • No specific • (+) proximal compression ultrasound
• DVT • S/Sx: unilateral pain and edema of thrombotic syndrome recommendat → initiate treatment
• PE an extremity, discoloration of leg from venous ions for • Anticoagulation regimen:
• Adapted mechanism to prevent excessive • PE: Homan’s sign (pain on hypertension due to antepartum o Enoxaparin
bleeding during delivery dorsiflexion) thrombotic obstruction testing o LMWH once or twice daily –
Virchow’s Changes in Mechanis • Proximal compression ultrasound which presents with Breastfeeding: stimulates antirhombin III and
Pregnancy PULMONARY EMBOLISM s/sx of chronic venous • LMWH, UFH inhibits factor X
Hypercoag clotting fibrinogen • Dyspnea, chest pain, cough, insufficiency and warfarin ▪ Does not cross placenta
anticoag (factor II) and syncope, hemoptysis • PE: risk of death, are • Women receiving anticoagulation
fibrinolysis factors V, VII, VIII,
• PE: tachypnea, tachycardia, pulmonary compatible may be converted from LMWH to
IX, X and XII
accentuated pulmonic closure hypertension, right Contraceptive: shorter half life UFH in anticipation
Decrease
fibrinolysis sound, rales, friction rub ventricular failure • Options for of delivery depending on
Venous Venodilation Progesterone • Labs: right axis deviation and women at risk institutional protocols (to decrease
stasis induced and Twave inversion on ECG, for VTE risk of hematoma on induction of
compression by atelectasis, infiltrates or effusion include IUD, anesthesia)
gravid uterus on CXR, hypoxemia on ABG progestin • For women on prophylactic LMWH:
Vascular Venodilation During delivery • V/Q scan implants discontinue at least 12 hours before
damage • Barriers – but
• CTPA – GOLD STANDARD for ruling scheduled induction of labor or CS,
out PE less effective 24hrs for those on an adjusted dose
regimen → pneumatic compression
POSTPARTUM
• Resumption of anticoagulation no
sooner than 4-6hrs after NSD or 6-
12hrs after CS
POSTPARTUM ANTICOAGULATION
• Prophylactic, intermediate or
adjusted dose LMWH for 6-8 weeks
• Oral anticoags may be considered
based upon planned duration of
therapy, lactation and patient
preference

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CONNECTIVE TISSUE DISORDERS
DISEASE ETIOLOGY AND PATHOPHYSIO
APAS An autoantibody-mediated
acquired thrombophilia with
recurrent thrombosis or
pregnancy morbidity and
documented presence of
antiphospholipid antibodies
Incidence: 11% of healthy
pregnancies, 70% of definite
APAS patients
• Thrombosis of placental
vessels
• Interference with coagulation
factors
• Inhibition of proliferation of
trophoblast
• Complement activation
SLE Chronic multisystemic
immunologic disorder
supported by the presence of
autoantibodies in patients with
clinical manifestations
DIAGNOSIS COMPLICATIONS PREGNANCY CONSIDERATIONS TREATMENT
Labs: Maternal: • Early utz → CAS → ff up scans every 4 • Low dose aspirin
• ACA IgG, IgM • Venous/arterial weeks → NST/BPS at 32 weeks (75-100mg/day)
• Lupus anticoagulant (LA) thrombosis • Calcium and Vitamin D • UFH or LMWH
• B2GP-1 IgG, IgM • Pre-eclampsia 18-48% • If on LMWH, sswitch to UFH at 36 weeks to • Enoxaparin
• Confirm after 12 weeks • Autoimmune allow Regional anesthesia • Until 6 weeks
• Vascular thrombosis thrombocytopenia • Consider delivery at 39 to 39 6/7 weeks to postpartum
• At least 1 clinical and 1 laboratory criteria • Other medical control timing of anticoag discontinuation
• Labs must occur 2x within 12 weeks apart complications:
and in a span of 5 years hemolytic anemia,
• LA: >2 occasions at least 12 weeks apart cutaneous, ulcers,
• Anticardiolipin antibody IgG/IgM present as transverse myelitis
>40 GPL or MPL >99TH percentile on Fetal:
2+occasions at least 12 weeks apart • Pregnancy loss and
• Anti b2 glycoprotein-I of IgG and IgM in fetal death
serum plasma present 2+ occasions at least • FGR
12 weeks apart • Preterm birth
• Abruptio
4 out of the 11 criteria Maternal: Effect of Pregnancy on SLE • No cure
• Lupus flare • Overall rate of lupus flare is 26.5% • ¼ of pregnant
• Lupus nephritis • Flares can occur at any trimester women have life
Effect of SLE on Pregnancy
• HPN threatening
• Pregnancy can worsen renal function
• PTB • Overall rate of renal flare is 16%
disease
• Hema complications • Difficult to differentiate lupus flare with
Fetal: nephropathy from severe pre-ec
• 1st trim loss Pre-conceptional Care:
• Fetal death • Start pregnancy during remission
• Cong heart block • Evaluate endorgan damage
• Assess/manage concurrent comorbids
• Neonatal lupus
• Optimize meds
• Counsel re complications
Antepartum:
• Multidsicplinary team
• First trimester for dating, CAS, fetal echo at 20-
22 weeks (+SSA/SSB)
• If (+) SSA/SSB weekly pr interval measurements
Intrapartum:
• Delivery at 39-39 6/7 weeks
• Vaginal delivery ideal, CS for ob indications
• Contraception counseling
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NEUROLOGIC DISORDERS
DISEASE ETIOLOGY AND PATHOPHYSIO DIAGNOSIS COMPLICATIONS PREGNANCY CONSIDERATIONS TREATMENT
Seizure • Paroxysmal disorder of the CNS • Symptoms: “aura” Maternal: • 2/3 will not have seizure deterioration in • Contraindicated AEDs in
Disorders characterized by abnormal neuronal • LABS: EEG, imaging of • SAB pregnancy pregnancy (Cat D)
discharge with or without loss of brain, labs as • Hemorrhage • Concentration of some AEDs affected by: o Phenytoin
consciousness indicated by maternal • HPN • Increased renal clearance and CP450 enzyme o Carbamazepine
• Paroxysmal discharges of neurons history • PTB activity o Valproic acid
occur when threshold for firing of • Epilepsy: at least 2 • CS • Decreased protein bindings → increased o Phenobarbital
neuronal membranes is reduced unprovoked seizures • PPD unbound biologically active form o Topiramate
>24 hrs apart or one • Death Prenatal Care: • Aim for monotherapy
unproved seizure and Fetal: • Folic acid 2-4mg/day with lowest amount
a probability of • FGR • First trimester scan for dating possible
further seizures • Congenital malformations • Anatomic scan at 11-13 wks CONTRACEPTIVE:
similar to general • Prenatal testing for AFP • Copper IUD
recurrence risk after 2 • CAS at 18-20 weeks • LNG-IUS
unprovoked seizures, • Fetal echo 22 weeks • DMPA injections
occurring over the Delivery: • AEDs lower estrogen
next 10 years • Continue AED during labor and immediate
postpartum
Postpartum
• BF is not contraindicated
MDD • Sustained depressed mood or loss of • Postpartum blues: pp day 2-4, resolve in 2 weeks • Refer to psych
interest in ADL along with • PP depression: 20%, peripartum (up to 6 weeks PP, sx of MDD) • Psychotherapy
neurovegetative symptoms of • Postpartum psychosis: mood lability, agitation, confusion, thought disorganization, hallucinations, • Antidepressants
depression disturbed sleep, increased risk of suicide, infant neglect, infanticide; Most commonly seen in mothers • Modd stabilizers
• Multifactorial and prompted by genetic with bipolar depression
and environmental factors • Edinburgh Postnatal Depression Scale – recommended scale
• Strongest risk factor for depression
during pregnancy is a history of MDD
Bipolar • Episodes of depression alternating with • Watch out for Preterm delivery • Mood episodes occur in 22.7% of pregnant • Psychotherapy
sustained episodes of elevated mood symptoms Severe SGA at birth women often depressive rather than • Drugs: SSRI for a min of 6
and/or irritability Neonatal morbidity (RDS, mani/hypomanic months
• Risk factors: family history, prior sepsis, neonatal • Risk of recurrence if mood stabilizer tx is • Aim: minimal number of
history of PP psychosis, primiparity, abstinence) discontinued shortly before pregnancy meds
postpartum Childhood pschopathology • Paroxetine – category D

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DERMATOLOGIC DISORDERS
Physiologic skin changes in pregnancy:
Pigmentation
• Linea nigra
• Secondary areola
• Melasma
Glands:
• Eccrine: miliaria, hyperhidrosis
• Apocrine: decreased activity
• Sebaceous: increased
Vasculature:
• Spider nevi, telangiectasia, palmar erythema, varicosities, vasomotor instability, increase capillary permeability
Connective tissue:
• Striae gravidarum
• Skin tags
DISEASE CHARACTERISTIC LESIONS DIAGNOSIS PREGNANCY PREGNANCY CONSIDERATIONS TREATMENT
OUTCOME
Intrahepatic • No primary lesion, may have • Affected areas: scalp, anus, • Increased risk of • 60-70% in future pregnancy • Ursodeoxycholic
cholestasis of secondary excoriations vulva and abdominal skin stillbirth, fetal • Delivery at 37-37 6/7 weeks esp in severe • Topical emollients
pregnancy • Elevated serum bile acids distress, PPH cases • Sedating antihistamines
• Spontaneous relief within 4 • Vitamin K to prevent PPH – not strong
weeks postpartum evidence
Pruritic urticarial • Patchy or generalized • Affected areas: abdominal • None • Recurrence rarely occurs • Topical emollients
papules and erythematous pruritic striae with periumbilical • No scarring in skin • Antihistamines
plaques of papules or plaques sparing, can progress to • Oral steroids
pregnancy (PUPPP) trunk extremities, but
spares palms, soles and
face
Atopic eruptions of • Dry, red scaly patches, • Affected areas: Face, neck, • None • Limited data on recurrence • Topical emollients
pregnancy (AEP) pruritic red papules chest, extensor surfaces of • Topical antipruritics
limbs and trunk • Topical steroids
• Antihistamines
Pemphigoid • Erythematous pruritic • Affected areas: abdomen • • Preterm birth • Topical/oral steroids
gestationis papules, plaques, veiscles often with umbilical • FGR • Antihistamines
• 2nd trimester involvement, extremities • Transient neonatal lesions • Immunosuppressants
• May recur with earlier onset and increasd
severity

127
NEOPLASTIC DISEASES
CANCER DIAGNOSED IN PREGNANCY:
• Avoid delay in diagnosis
• Postpone radiologic studies that will not alter ca treatment or patient decision during pregnancy
• Avoid iatrogenic preterm deliveries
• Choose a chemotherapeutic regimen with the most experience of use and safety
• At least 3 weeks between cycle of chemo during pregnancy and delivery
• Halt / complete chemo by 34-35 weeks
• Send placental pathology for all cancers, esp in melanoma
• Close multidisciplinary management with an oncologist and MFM specialist
• Women previously treated with chemo, radio or both are not an increased risk of having children with congenital or chromosomal anomalies
• Women who received prior irradiation can have perinatal complications (miscarriage, PTB, LBW, placenta accrete)
• Pregnancy does not affect the risk of recurrence of any type of cancer (except GTN)
• Women with left sided chest radiotherapy or anthracycline based chemo should undergo cardiac evaluation prior to pregnancy

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