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Diabetes in Pregnancy
MDSC5004 - Senior O&G Clerkship
September 15th 2016

Duncan Jackson
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Outline
n Definition & Classification
n Incidence & Epidemiology

n Aetiology

n Pathophysiology

n Fetal & Maternal Complications

n Clinical Features
n Investigations

n Treatment & Management

+ Definition, Classification &
Epidemiology
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What is Diabetes Mellitus?

n Clinical syndrome characterized by hyperglycaemia

n Due to absolute or relative insulin deficiency

n Gestational diabetes mellitus (GDM)

n Carbohydrate intolerance with onset or 1st recognition during
pregnancy
n Exaggerated physiologic changes in glucose homeostasis
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Etiologic Classification of DM
(ADA, 2012)
n I. Type 1 DM III. Other:
n Absolute insulin deficiency (2o β-cell
destruction) n Monogenetic
n MODY 1-6
n Immune-mediated or Idiopathic

n Mitochondrial
n II. Type 2 DM
n Relative insulin deficiency & insulin resistance n Secondary causes
n Pancreatitis, CF
n IV. Gestational DM n Glucocorticoids &
n Glucose intolerance in subsequent years other drugs
occurs more frequently n Endocrinopathies
n 50% of women will develop T2DM within 22- n Infections
28 years (ACOG, 2013)
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White Classification in Pregnancy
+ Diagnosis (Outside of Pregnancy) – WHO
Classification of abnormal glucose tolerance
n Diabetes
n FBG ≥ 7.0 mmol/L (126 mg/dL)
n 2-hr-PP 75g OGTT ≥ 11.1 mmol/L (200 mg/dL)
n HbA1C ≥ 6.5%
n RBG ≥ 11.1 mmol/L + classic symptoms of hyperglycemia

n Abnormal Glucose Homeostasis (Pre-diabetes)

n Impaired Fasting Glucose:
n FBG = 5.6 – 6.9 mmol/L (100-125 mg/dL)
n Impaired Glucose Tolerance:
n 2-hr-PP 75g OGTT = 7.8 – 11.1 mmol/L (140 – 199 mg/dL)
n HbA1C = 5.7 – 6.4%
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How is GDM diagnosed?
n Screening of all women not known to have glucose intolerance
earlier in pregnancy, at 24-28 weeks
n Early T2DM screening advocated in high-risk women:
n Prior hx of GDM or delivery of LGA infant
n Impaired glucose tolerance, glucosuria
n Obesity (BMI > 30 kg/m2)
n PCOS
n Strong family hx of T2DM

n N.B. If T2DM is not diagnosed, repeat screening at 24-28 weeks or at

any time symptoms or signs suggest hyperglycaemia
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How is GDM diagnosed?
Two-step approach One-step approach - IADPSG
(ACOG & ADA 2013) Consensus Panel (2010)
n O’Sullivan’s test n 75-g, 2-hour OGTT
n > 7.5mmol/L [135mg/dl] or
n > 7.8 mmol/L [140 mg/dl]
n Subsequent diagnostic 75g 2-hr OGTT
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NICE Management Guidelines
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Epidemiology
n In Jamaica:
n Prevalence of DM 7.9%, & 2.8% for
impaired fasting glucose (Wilks et al,
2008)
n Incidence – 12.0% with family hx of T2DM
& 1.5% without family hx (Irving et al.,
2008)

n In the US, ~7% of pregnancies are

complicated by either GDM or pre-
GDM (Beckmann, 2013)

n GDM thought to affect 2% - 14% of all

pregnancies (ACOG, 2001)

n Recent years, rise in prevalence of DM

in pregnancy which reflects increases
in both Pre-gestational T2DM & GDM
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Aetiology & Pathophysiology
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GDM Risk Factors – Pre-existing
n Maternal Age > 30years
n Ethnicity – African, Hispanic,
Native American, Asian
n Obesity (BMI>30)
n Obstetrical Hx of GDM or
Macrosomia (≥ 4000g)
n Strong Family Hx of DM (1O
relatives)
n HbA1C ≥ 5.7%, IGT, or IFG on
previous testing
n Other clinical considerations
associated with insulin
resistance e.g. Ancanthosis
nigricans
ADA. Diabetes Care 2013
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GDM Risk Factors – Occurring in
this Pregnancy
n Glycosuria at 1st antenatal visit n Physical Inactivity

n Current Obstetric Problems – n Certain dietary patterns

n Essential HTN, PIH, hx of
CVD n PCOS
n Polyhydramnios, LGA n Biochemical markers –
n Current use of steroids adiponectin & CRP

ADA. Diabetes Care 2013

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Physiology of Glucose Metabolism
During Pregnancy
n Pregnancy predisposes to persistent hypergylcaemia

n Factors that oppose insulin action during pregnancy

n ↑ Placental hormones (2nd trimester) –
n hPL, placental insulinase, Glucagon,↑Plasma cortisol
n Progesterone

n Further aggravated by ↑body weight and ↑caloric intake during pregnancy

n Pre-gestational diabetes becomes worse during pregnancy

n GDM develops when pancreatic insulin output cannot overcome the

effect of these hormones
n 3 – 5% unable to maintain normoglycaemia
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Pathophysiology
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Pregnancy and Diabetes
Diabetogenic effect of pregnancy

Effect of pregnancy on pre-existing diabetes and IGT

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Physiological actions of Insulin on
the foetus:
n Anabolic Hormone
n Promotes the uptake of glucose into muscle and liver tissue
n Promotes fatty acid and triglyceride synthesis
n Promotes protein synthesis
n Promotes cell proliferation
n Promotes somatic and visceral growth and development
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Fetal & Maternal Complications
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Fetal Morbidity & Mortality
Congenital Anomalies:
n CNS n MSK
n Open NTD e.g. anencephaly, n Sacral agenesis (pathognomonic)
macrocephaly n Caudal regression sequence

n Cardiac n GI
n Cardiomyopathy, TGA, VSD, ASD,
n Duodenal atresia
Coarctation of aorta n small left colon syndrome

n Renal n Chromosomal abnormalities

n Typically due to Advanced Maternal
n Hydronephrosis, Renal agenesis Age
n Ureteral duplication n Down’s Syndrome

(Hyperglycaemia & Adverse Pregnancy

Outcome Study, 2008) n Others – single umbilical artery
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Fetal Morbidity & Mortality –
Cont’d
n Altered Fetal Growth n Metabolic
n Fetal Macrosomia (>4000g) n Neonatal Hypogylcaemia
n LGA n Neonatal Hyperbilirubinemia
n IUGR (particularly w/ pre- n Polycythemia
GDM) n Hypocalcemia
n Prematurity
n Shoulder Dystocia
n Polyhydramnios n Brachial plexus injury
n AFI > 24cm n Birth asphyxia

(HAPO Study, 2008)

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Fetal Morbidity & Mortality –
Cont’d
n Increased Perinatal morbidity n Complications later on in
and mortality adolescence / adulthood
n Respiratory Distress n Obesity
Syndrome n DM
n Spontaneous Abortion & n Reproductive problems
Stillbirth
n Metabolic Syndrome
n Hypothermia to2o
prematurity & insufficient fat
(HAPO Study, 2008)
(Cho et. Al, 2016)
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Maternal Complications -
Antenatal
n Obstetric Complications – PIH, n End-organ Involvement or
Pre-eclampsia
deterioration –
n Pre-GDM >> GDM
n Vasculitides or comorbid n Nephropathy, proliferative
chronic HTN retinopathy
n Micro/macroangiopathy
n Diabetic Emergencies
n Risks of DKA and coma
n Infections – vaginal
n Hypoglycemia esp. early in
pregnancy candidiasis
n Nausea and Vomiting may
interfere with caloric intake
n Autonomic neuropathy
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Maternal Complications - Delivery

n Prolongation of labour & increased instrumentation rates

n Traumatic births – e.g. shoulder dystocia leading to perineal

injuries

n Operative Delivery

n Polyhydramnios – PROM, Cord Prolapse

n Infections – puerperal sepsis

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Maternal Complications -
Postpartum
n Increased risk of developing DM later in life

n Past hx of GDM increases the risk of recurrence in

subsequent pregnancies
+ Clinical Significance of Distinguishing
between GDM & Antecedent DM
n GDM
n Mothers at risk of future development of T2DM & metabolic syndrome
n Less likely to have congenital defects
n Usually no effect on organogenesis
n Increases risk of Macrosomia, Caesarian Section

n Pre-gestational DM
n More likely to have congenital abnormalities
n Complications during organogenesis (1st trimester)
n Assoc. w/ risk of IUGR, Pre-eclampsia, PPROM, PTL, polyhydramnios,
macrosomia
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Clinical Features
+ Clinical Features – Symptomatology

n Only 20% of women with significant glucose intolerance during

pregnancy exhibit glycosuria and other symptoms

n Insidious onset:
n Polyphagia, Polydipsia, (polyuria)
n DKA – Vague symptoms of fatigue, abdominal discomfort, weight loss
n Nausea, vomiting
n Fever
n Burning sensation during voiding
n Vaginal discharge, recurrent candidiasis

n Stigmata of microvascular & macrovascular disease with established DM

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Clinical Features - Hx
Identify Risk Factors:
n Personal Hx T1DM or T2DM n Advanced Maternal age
+/- complications, GDM (>35yrs)

n T1DM may present with n Obesity

hypoglycemic coma as the 1st
“sign” of pregnancy! n Ethnicity

n Positive family Hx of DM – 1O n High Parity

relative
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Clinical Features - Hx
Risk Factor’s Cont’d:
n Recurrent 1st spontaneous abortions (esp. 3 or more)

n Previous birth of a macrosomic infant

n Previous unexplained stillbirths or neonatal deaths

n Previous infant with congenital abnormalities (CVS, CNS and

musculoskeletal)
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Investigations & Management
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Management
n Preconception Counseling (ideally)
n Optimize Glucose control prior to pregnancy

n Antenatal Follow up
n Early Booking
n Screening for fetal & maternal complications
n Diet and Glucose Monitoring
n Medical Therapy

n Labor & Delivery of the patient with DM

n Family Planning
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Pre-conception Counseling
n 3 months prior to conception ideally

n Lifestyle advice – exercise, diet

n High-dose (4-5mg) folic acid supplementation

n Prior to and up to 12 weeks following conception

n Review of potentially harmful drugs

n ACEi, ARBs, & HMG-CoA reductase inhibitors C/I in pregnancy
n Sulfonylureas C/I in pregnancy

n Reassurance that with good glycemic control, risks associated with DM

in pregnancy can be reduced
n Overall 95% of women with pre-GDM give birth to a healthy infant
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Dietary Advice for DM in
pregnancy
n Less weight gain – in overweight or obese mothers
n Beneficial effect on perinatal outcomes in obese women

n Nutritional Therapy & access to dietician

n Limit CHO & caloric intake – high-fiber, low GI-foods
n 1800 - 2500 Kcal/day (complex CHOs / protein / fat = 40:20:40)
n Ideal BW - 30-35 kcal/kg/day
n Underweight - Up to 40kcal/kg/day
n Overweight – 22-25 kcal/kg/day
n Morbidly obese – 12 – 14 kcal/kg/day
n 3 small-to-moderate sized meals and 2-4 snacks
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Pre-conception Counseling –
Cont’d
n Screen & Monitor for microvascular disease
n Retinopathy (worsens in 15%) – laser coagulation if
proliferative
n Severe nephropathy (>2g per 24 hour) –↑risk of
preeclampsia & preterm birth
n Microalbuminuria and lesser degrees of proteinuria - ↑risk
of PIH

n Macrovascular disease and premature coronary artery

disease
n ECG & Cardiology referral prior to pregnancy
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Home Glucose Monitoring
n Self-monitoring of blood glucose at home 4 times daily
n On awakening & 1 hour after meals
n Admission may be necessary for profiling & stabilization

Aim to achieve pre-pregnancy guideline

glycaemic targets (ADA)
• HbA1C < 7%
• FBG < 5.6 mmol/L (100 mg/dL)
• 2-hr PP <7.8 mmol/L (140 mg/dL)
• Mean daily glucose
concentrations <110 mg/dL
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Pre-conception Counseling –
Cont’d

n Plan for Antenatal care

n Antenatal visits 2-week intervals for the 1st two trimesters

and then once weekly for the 3rd trimester
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Investigations – First Trimester
(LMP – 12+6 weeks)
n Booking Parameters n Other Investigations
n CBC n Dating U/S – 10-14 weeks
n Hb – Start on haematinics n T1 Screening for Down’s – “Combined
n WBC Test” (11 – 13+6 weeks)
n Platelet n PAPP-A, β-hCG, NT
n Serology – HIV, VDRL n Screening for DM complications
n Sickle, Rubella susceptibility
n U&Es, BUN, Cr
n Blood Group & Rhesus Factor
n Spot Urine protein-to-creatinine
n ± IDCT if Rhesus Negative ratio
n Urinalysis – albumin, glucosuria,
n Fundoscopy
nitrites
n BP, Booking weight
n HbA1C
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Investigations

n Other Screening Test for Gestational Diabetes

n O’Sullivan’s Test (24-28 weeks)
n 2 hour-PP 75g OGTT – whenever earlier screening test are
positive
n (Amniotic fluid and/or cord blood insulin levels)
n (Serum fructosamine)
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Investigations – 2nd Trimester
(13+0 – 28+6 weeks)
Pre-eclamptic panel if suspected
n Repeat spot urine protein-to-
creatinine n CBC, BUN, Cr, LFTs
n Uric acid
n HbA1c
n 24-hr urine collection

n NST, amniotic fluid index,

fetal growth / biometry
n Doppler ultrasonography
n Umbilical cord
n MCA
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Investigations – 2nd Trimester
(13+0 – 28+6 weeks)
n Antepartum Fetal Assessment
n Anomaly Scan for structural defects – 18 - 20 weeks
n Echocardiography (24 weeks) may also be done if suspected cardiac
defects

n Counseling about Quad Screen

n AFP,β-hCG, unconjugated estriol, inhibin A

n U/S Scans
n Monthly from 24wks to monitor fetal growth (macrosomia)
n Exclude / confirm polyhydramnios
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Investigations – 3rd Trimester
(29 weeks – Delivery)
Antepartum Fetal Monitoring (32-34 weeks*):

n Fetal kick charts / movement counting

n U/S Growth Scan (~30 weeks):

n BPD, HC, AC, FL

n Biophysical method (NST, Doppler & BPP) – after 34 weeks

n Contraction stress test

n ± Amniocentesis – fetal lung maturity

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Indications for Hospitalization
n Stabilization of DM state n Preterm labour, PROM
n HbA1C, FBG
n Education n Pyelonephritis
n Polyhydramnios &
n Electively at 36 weeks in
macrosomia may be
indicative of poor glycaemic preparation for delivery
control
n Fetal distress for biophysical
n Ketoacidosis assessment

n Pre-eclampsia
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Pharmacologic Therapy – Selected
Oral Hypoglycemic Agents
n Previously thought to be teratogenic

n Glyburide – does not cross the placenta and recent trials suggest that it
is safe

n ACOG (2013) acknowledges that both glyburide and metformin (T2 &
T3) are appropriate, as is insulin, for 1st line glycemic control in women
with gestational diabetes

n **However, because long-term outcomes have not been studied,

committee recommends appropriate counseling when OHAs are used

n Older sulfonylureas are contraindicated – crosses placenta

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Pharmacologic Therapy – Insulin
n Indications:
n Diet alone is inadequate to control the blood glucose levels
n Patient with type I DM
n To replace C/I OHAs e.g. sulfonylureas in T2DM

n Insulin Requirements by Trimester

n T1 – 0.7 U/kg/day
n T2 – 0.8 U/kg/day
n T3 – 0.9 – 1.0 U/kg /day
n *In severely obese women, initial doses may be up to 1.5 – 2 U/k/day
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Insulin Regime
n Once control is satisfactory or euglycaemia has been achieved,
Split Dose Regime can be given:
n Total daily insulin requirement = 0.7 – 1.2 U/kg

n Moring Dose (2/3 of TDD)

n 2/3 short-acting insulin + 1/3 intermediate-acting insulin

n Evening Dose (1/3 of TDD)

n ½ short-acting insulin + ½ intermediate-acting insulin

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Timing and Mode of Delivery

n Spontaneous

n Induced –
n prostaglandin
n AROM
n Syntocin

n Caesarean section
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Timing and Mode of Delivery –
Cont’d
n Preferred mode of delivery is vaginal
n Provided pelvis is adequate and fetus is not macrosomic
n Good glycaemic control with no obstetric or other medical contra-
indications
n e.g. breech presentation, severe preeclampsia
n N.B. Diabetes itself is NOT an indication for C-section

n Indications for delivery prior to 38 weeks:

n Severe pre-eclampsia
n Progressive proliferative retinopathy
n Renal failure
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Intrapartum Care
n Obtain FBG level
n Once in active labour: Serial
RBG (q1-2hrly) + 5% dextrose
+ insulin given as needed
n Close surveillance &
continuous electronic fetal
monitoring
n Skilled birth attendant &
Neonatologist
n Anticipate perinatal
morbidity
n Macrosomia, hypothermia,
metabolic derrangements
etc.
n Emergency C–section if failure
to progress exists
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DM & Induction of Labour

n Induction at 38 weeks gestation to avoid risk of late stillbirths

(up to 39 – 40 wks if good glycaemic control on diet)

n If poor glycemic control, assess lung maturity before

delivery
n Corticosteroids - dexamethasone

n Aim to deliver within 12 hrs of induction

n Increased risk of ketoacidosis >12 hrs
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DM & Induction
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DM & Caesarian Section –
Indications
n Early primigravida
n Multigravida with bad
obstetric hx
n Obstetric complications
n Pre-eclampsia
n Polyhydramnios
n Malpresentation
n DM with complications or
difficult to control
n Fetal macrosomia (>4000g),
CPD
n N.B. macrosomia in U.S. is
5000g for Caucasian-based
population (& 4500g for DM
mothers)
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DM & C-Section
n Preoperative considerations
n Pt should take evening dose of
NPH night before procedure
n Withhold morning dose
n IV 5% DW with blood glucose
monitoring q2hrly, or as
necessary
n ± insulin infusion to maintain
normoglycemia
n Epidural analgesia if available
n Close monitoring of FHR &
maternal vitals
n Intraoperative considerations:
n Maintain normoglycaemia
n Postoperative considerations:
n Reassess glycemic control after
delivery
n Prophylaxis – Antibiotics &
Heparin SC
n Anti-inflammatory and Analgesia
n Anti-emetics
n Vitals 1-2 hrly & hourly urine
output
n ~3-4L IV crystalloids in 1st 24
hours
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Postpartum Care
n Medical:
n Maternal insulin requirements decreases precipitously
n Glucose monitoring: 4,8,12 and 24 hours w/ insulin administered as needed
n Monitor up to 72 hours after delivery to exclude persistent hyperglycaemia

n Evaluate need for NICU admission

n RBG of neonate within 2 hrs of birth
n Transition pre-GDM pts to appropriate treatment (e.g. OHA or adjusted insulin
regime)

n Obstetric
n PPH, Infections – genital, UTI, perineal wounds
n Lactation support
n Grief counseling in cases of perinatal loss
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Post-partum Care

n Reassess blood glucose levels 6-12 weeks after delivery

n If negative → GDM
n If positive → overt, previously unrecognized DM →
endocrinology & dietician referral
n If IFG or IGT, pt should undergo annual testing for DM
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Family Planning

n Discuss realistic goals on family size

n Discuss Contraception – No absolute contraindications to any

method
n Combined OCP may deteriorate glycemic control; recurrent
vaginal candidiasis
n IUD good alternative if comorbidities of obesity, HTN, or
dyslipidemia exist
n Tubal ligation at CS or postpartum
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Summary
n Women in whom GDM is diagnosed should be treated with nutrition
therapy and, when necessary, medication for both fetal and maternal
benefit. (Level A Evidence)

n All pregnant patients should be screened for GDM, whether by the

patient’s medical history, clinical risk factors, or laboratory screening
test results to determine blood glucose levels. (Level B Evidence)

n Women with GDM should be counseled regarding the option of

scheduled cesarean delivery when the estimated fetal weight is 4,500 g
or more. (Level B Evidence)

n Women with GDM with good glycemic control and no other

complications can be managed expectantly. (Level C Evidence)

n ACOG, 2013
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References
n Cunningham, F. G., Leveno, K. J., Bloom, S. L., Spong, C. Y., Dashe, J. S., Hoffman, B. L., Casey, B. M., ...
Sheffield, J. S. (2014). Williams Obstetrics, 24th ed. New York [etc.]: McGraw-Hill Medical.

n Dewhurst, J., & Edmonds, D. K. (2012). Dewhurst's Textbook of Obstetrics & Gynaecology. Chichester, West
Sussex: Wiley-Blackwell.

n Roopnarinesingh, S., Roopnarinesingh, A., Sirjusingh, A., Bassaw, B., & Roopnarinesingh, R. (2008). Textbook of
obstetrics. Port of Spain, Trinidad & Tobago: Lexicon

n Ferguson, T. S.; Tulloch-Reid, M.K. and Wilks, R.J. (20101). The epidemiology of diabetes mellitus in
Jamaica and the Caribbean: a historical review. West Indian med. j. [online], vol.59, n.3 [cited 2016-09-12],
pp. 259-264 . Available from: <http://caribbean.scielo.org/scielo.php?script=sci_arttext&pid=S0043-
31442010000300007&lng=en&nrm=iso>. ISSN 0043-3144.

n Cho, Hee Young, Inkyung Jung, and So Kim Jung. (2016). "The Association between Maternal Hyperglycemia
and Perinatal Outcomes in Gestational Diabetes Mellitus Patients." Medicine 95.36: n. pag. Web. 15 Sept. 2016.

n Practice Bulletin No. 137. Gestational diabetes mellitus. Obstet Gynecol. 2013;122:406–16