CASE 1: A 24 year old who had a history of smoking 2 packs a day and heavy

alcohol intake for the for the past years up to the present got pregnant . What
could be the effects of alcohol and smoking on her fetus?

According to Sadler (2012), congenital anomalies arise not only from

hereditary factors but also from environmental factors. The exposure to several
toxic or chemical compounds can induce risks of birth defects. For the above
case, maternal alcohol ingestion can induce a broad spectrum of defects such
as intellectual disability to structural abnormalities. The term to describe alcohol-
defects is Fetal alcohol spectrum disorder (FASD). It is a severe condition which
includes structural defects, growth deficiency, and intellectual disability. In
addition, the Centers for Disease Control and Prevention (2022) suggests that
FASD occurs when alcohol in the mother’s blood passes to the baby through
the umbilical cord. The possibility of unintentional abortion may occur but when
born, a person with FASD might have low body weight, poor coordination,
hyperactive behavior, difficulty with attention, poor memory, difficulty in school,
learning disabilities, speech and language delays, intellectual disability, low IQ,
abnormal facial features, vision or hearing problems, etc..

When alcohol-defect includes involvement of the central nervous system,

Alcohol-related neurodevelopmental disorder (ARND) may arise. This refers to a
complex range of disabilities in neurodevelopment and behavior, adaptive
skills, and self-regulation in the presence of confirmed prenatal alcohol
exposure. Cigarette smoking, on the other hand, is linked to an increased risk
for orofacial clefts and contributes to intrauterine growth retardation and
premature delivery. Cigarette contains chemical agents which are considered
to be teratogens that can cause or raise the risk for birth defect or
malformation. Thus, avoidance of alcohol and cigarette during and prior to
conception reduces the incidence of birth defects.
CASE 2: Why is the embryonic period considered as a critical stage/period of
human development?

Figure 1. Critical Periods of Development

The most sensitive time of human development is during the embryonic

period because it is when the internal and external structures are formed. This
period commences from the third to the eight week of pregnancy and the
three germ layers, ectoderm, mesoderm, and endoderm, give rise to its own
tissues and organ systems. Exposures to harmful compounds, alcohol, and even
medication during this time can cause severe damage to the development of
body parts. Figure 1, retrieved from MotherToBaby (2022), summarizes the most
sensitive times of child development to defects throughout the 38 weeks of
pregnancy. It suggests that the brain and spinal cord is at the highest risk of
structural defects during embryonic period.

CASE 3: How are neural defects formed ? Describe the different types of NTDs
types of such.

Neurulation is the process where the neural plate arising from the
ectoderm forms the neural tube. It is completed when the central nervous
system is represented by a closed tubular structure which has a narrow caudal
portion and broader cephalic portion. These become the spinal cord and
brains vesicles, respectively. Neural tube defects (NTDs) may occur during the
end stages of neurulation specifically, when the closure of the neural tube fails
to occur. The following NTDs are described below:

ANENCEPHALY- occurs when neural tube fails to close at the cranial

region. In addition, during this time, most of the brain fails to form. This defect is
considered to be lethal and is diagnosed prenatally and pregnancies are
terminated.

SPINA BIFIDA- occurs when the closure fails anywhere from the cervical
region caudally. The most common site for this defect is in the lumbosacral
region. Moreover, children with this defect lose a degree of neurological
function based on the spinal cord level of the lesion and its severity.

CASE 4: Explain the 2 ways how are blood vessels formed and how are capillary
hemangiomas formed. Give the treatment.

The germ cell layer, mesoderm, gives rise to the blood vessels. Blood
vessels emerge from the endothelial cells which associate into tubular structures
and other cell types until they are organized to make the vessel wall (Dieterlen-
Lievre and Pardanaud, 1992). The two ways how blood vessels are formed are
through vasculogenesis and angiogenesis.

Figure 2. Blood Vessel Formation via Vasculogenesis

VASCULOGENESIS- a process when blood vessels are formed from the

blood islands which arise from mesoderm cells that are induced to form
hemangioblasts, the precursor cell, with the aid of FGF2 (Figure 2). According
to Sidawy (2018), Hemangioblastic aggregates composed of an inner core
of hematopoietic stem cells and an outer rim of endothelial cells form in the yolk
sac. The hematopoietic stem cells serve as the source of blood cells to the embryo
until day 60, when the liver, spleen, thymus, and ultimately the bone marrow
become the source of blood cells. Hemangioblastic aggregates also form in the
connecting stalk and chorion at day 17, and coalesce to form the
extraembryonic umbilical vessels that will act as the circulatory connection
between the embryo and the maternal tissue. Furthermore, vascular endothelia
growth factor (VEGF) secreted by surrounding mesoderm direct hemangioblast
to form blood vessels.

Figure 3. Blood Vessel Formation via Angiogenesis

ANGIOGENESIS- blood vessel formation when they arise or sprout from

existing vessels. This formation of new vessel from a pre-existing vessel involves
sprouting or budding which include growth phases of the new vessel and its
stabilization and the intussusception when interstitial cell columns inserts into the
lumen of the pre-existing vessel to partition the vessel and remodel the local
vascular network ( Kubis & Levy, 2003). Like vasculogenesis, angiogenesis is also
regulated by VEGF (Figure 3). This growth factor stimulate the proliferation of
endothelial cells at points where new vessels will sprout from existing ones
(Sadler, 2012).

Capillary hemangiomas represent developmental hamartomatous

lesions of vascular tissue and their growth stops after certain period of time,
following which some of the hemangiomas may involute (Mishra et al., 2012).
These are abnormally dense collections of capillary blood vessels that form the
most common tumors of infancy. Furthermore, this is often associated with
craniofacial structures but may occur anywhere. Facial lesions may be focal or
diffuse which can cause more complications like ulcerations, scarring, and
airway obstruction as for the case of mandibular hemangiomas. According to
Koka & Patel (2022), this condition is most often asymptomatic and thus require
no intervention however, extreme cases causing nerve compression can be
managed through drugs and surgery. They suggest that beta-blockers such as
propranolol and timolol can suppress vascular endothelia growth factors
(VEGF) and Fibroblast growth factors (FGF) which are responsible for the
proliferation of such skin lesions. Moreover, these drugs can cause down-
regulation of cAMP needed for cell signaling and induce apoptosis of
proliferating cells. Lasers can be used to treat superficial hemangioma and aid
in diminishing and lightening the color of lesions. For vision-threatening
hemangioma, surgical debulking of the lesion is proposed but complete
removal is not recommended.

CASE 5: What factors could affect the embryonic period and describe the
defects it could produce.

The embryonic period is the most critical stage of human development.

During this time, different organ systems are formed and anomalies may also
occur. Birth defects, as suggest by Sadler (2012), are synonymous to structural,
behavioral, functional, and metabolic disorders present at birth. Moreover, these
congenital anomalies are not only primarily caused by hereditary factors but also
environmental factors. These environmental factors include infectious agents,
physical agents, chemical agents, and hormones. Collectively, these factors are
called teratogens and the degree of an agent to produce birth defects can be
determined through the principles of teratology: 1) Susceptibility to teratogenesis
depends on the genotype of the conceptus. The maternal genome also plays an
important role in drug metabolism, resistance to infection, and other processes
that can affect the conceptus; 2) exposure to teratogens during the most critical
stage of embryonic period; 3) Dose and duration of exposure to teratogen; 4)
ability of teratogens to initiate pathogenesis; and 5) Death, malformation, growth
retardation, and functional disorders as manifestations of abnormal
development. The table below also lifted from Sadler (2012) shows the possible
defects that can be produced from different types of teratogens.

Teratogen Congenital Malformations

Infectious agents
Rubella virus Cataracts, glaucoma, heart defects, hearing loss,
tooth abnormalities
Cytomegalovirus Microcephaly, visual impairment, intellectual
disability, fetal death
Herpes simplex virus Microphthalmia, microcephaly, retinal dysplasia
Varicella virus Skin scarring, limb hypoplasia, intellectual disability,
muscle atrophy
Toxoplasmosis Hydrocephalus, cerebral calcifications,
microphthalmia
Syphilis Intellectual disability, hearing loss
Physical agents
X-rays Microcephaly, spina bifida, cleft palate, limb defects
Hyperthermia Anencephaly, spina bifida, intellectual disability
Chemical agents
Thalidomide Limb defects, heart malformations
Aminopterin Anencephaly, hydrocephaly, cleft lip and palate
Diphenylhydantoin Fetal hydantoin syndrome: facial defects,
(phenytoin) intellectual disability
Valproic acid Neural tube defects; heart, craniofacial, and limb
anomalies
Trimethadione Cleft palate, heart defects, urogenital and skeletal
abnormalities
Lithium Heart malformations
SSRIs Heart malformations
Amphetamines Cleft lip and palate, heart defects
Warfarin Skeletal abnormalities (nasal hypoplasia, stippled
epiphyses)
ACE inhibitors Growth retardation, fetal death
Mycophenylate mofetil Cleft lip and palate, heart defects, microtia,
microcephaly
Alcohol Fetal alcohol syndrome (FAS), short palpebral
fissures, maxillary hypoplasia, heart defects,
intellectual disability
Isotretinoin (vitamin A) Isotretinoin embryopathy: small, abnormally shaped
ears, mandibular hypoplasia, cleft palate, heart
defects
Industrial solvents Low birth weight, craniofacial and neural tube
defects
Organic mercury Neurological symptoms similar to those of cerebral
palsy
Lead Growth retardation, neurological disorders
Hormones
Androgenic agents Masculinization of female genitalia: fused labia,
clitoral hypertrophy (ethisterone, norethisterone)
DES Malformation of the uterus, uterine tubes, and upper
vagina; vaginal cancer; malformed testes
Maternal diabetes Various malformations; heart and neural tube
defects most common
Maternal obesity Neural tube defects, heart defects, omphalocele
References:

Basics about FASDs. (2022, January 11). Centers for Disease Control and
Prevention. Retrieved October 16, 2022, from
https://www.cdc.gov/ncbddd/fasd/facts.html

Critical Periods of Development. (2022, April 20). Retrieved October 16, 2022, from
https://mothertobaby.org/fact-sheets/critical-periods-development/

Dieterlen-Lièvre, F., & Pardanaud, L. (1992). Embryonic development of blood

vessels. In Angiogenesis in Health and Disease (pp. 1-15). Springer, Boston,
MA.

Koka, K & Patel, BC. (2022). Capillary Infantile Hemangiomas. In: StatPearls.
StatPearls Publishing, Treasure Island (FL). PMID: 30855837.

Kubis, N., & Levy, B. I. (2003). Vasculogenesis and angiogenesis: molecular and
cellular controls. Part 1: growth factors. Interventional neuroradiology :
journal of peritherapeutic neuroradiology, surgical procedures and related
neurosciences, 9(3), 227–237. https://doi.org/10.1177/159101990300900301

Mishra, M. B., Bishen, K. A., & Yadav, A. (2012). Capillary hemangioma: An

occasional growth of attached gingiva. Journal of Indian Society of
Periodontology, 16(4), 592–596. https://doi.org/10.4103/0972-124X.106924

Sadler, T. W. (2012). Langman’s Medical Embryology (12th ed.). Philadelphia, US:

Lippincott Williams & Wilkins. 117-126.

Sidawy, A. P., & Perler, B. A. (2018). Rutherford's vascular surgery and

endovascular therapy. Elsevier health sciences.