Diabetes & Pregnancy By: Carolyn Connors

1. Diabetes & PregnancyBy: Carolyn Connors

2. Diabetics and Pregnancy • Euglycemia is very important! • Decreases likelihood of: • Miscarriage • Congenital anomalies • Macrosomia • Fetal death • Neonatal morbidity

3. Diabetic Embryopathy • Occurs in 6-7th weeks GA • Maternal Hyperglycemia leads to vascular disruption and yolk sac failure • Increased spontaneous abortions • Major malformations

4. Fetal Effects • Pathophysiology – Maternal hyperglycemia Fetal hyperglycemia Premature maturation of pancreatic islets Hypertrophy of beta cells Hyperinsulinemia

5. Hypertrophy of Beta Cells

6. Fetal Hypoxemia • Chronic fetal hyperinsulinemia • Increased activity hepatic enzymes • Increased glycogen and lipid storage • Increased metabolic rates • Oxygen consumption increased

7. Fetal Hypoxemia • Stimulates erythropoietin • polycythemia • Promotes catecholamine production • HTN • Cardiac hypertrophy • Contributes 20-30% stillbirth rate in poorly controlled diabetics

8. Neonatal Effects • Congenital anomalies – • Accounts for 50% of perinatal deaths of infants of diabetic mothers (IDM) • Relative risk increased 7% with IDM over general population

9. Congenital Anomalies • Two-thirds involve CVS or CNS • Anencephaly and Spina bifida 20x more common in IDM • GU, GI, MSK defects increased

10. Congenital Anomalies • Left Colon Syndrome - • Transient inability to pass meconium • Resolves spontaneously • Condition unique to IDM’s

11. Congential Anomalies • Caudal Regression Syndrome – • 200x more common in IDM • Incomplete development of sacrum/lumbar region • Distal spinal cord disrupted • Neurologic impairment varied • Leg deformities

12. Premature Delivery • Increased Iatrogenic premature delivery • Maternal preeclampsia • Increased spontaneous premature labour • Associated with poor glycemic control • High rates of UTI’s

13. Perinatal Asphyxia • Defined to include: • Fetal heart rate abnormalities during labor • Low Apgar scores • Intrauterine death

14. Perinatal Asphyxia • Correlated with: • Maternal vascular disease • Eg: nephropathy • Hyperglycemia during labor • Prematurity

15. Increased Fetal Growth • Mostly during 3rd trimester • Disproportionate growth • Insulin sensitive tissue eg. Liver, muscle, cardiac muscle, subcutaneous fat • Head circumference normal • Increased risk of hyperbilirubemia, hypoglycemia, acidosis

16. Macrosomia

17. Macrosomia • Birth weight > 90th percentile or > 4000g • Predisposes to birth injury • Eg: Shoulder Dystocia • Brachial plexus injury • Clavicular/Humeral Fractures • Perinatal asphyxia

18. Shoulder Dystocia

19. Shoulder Dystocia • Occurs in 1/3 IDM > 4000g • Disproportionate growth contributes • C-Section often recommended if fetal weight > 4300g

20. Intrauterine Growth Restriction • Maternal Vasculopathy • Preclampsia • Congenital Anomalies • Very strict BG control

21. Respiratory Distress Syndrome • Causes amoung IDM: • Delayed maturation of surfactant synthesis • Hypertrophic cardiomyopathy • Retained lung fluid (TTN) • Increased rates of c-section

22. Hypertrophic Cardiomyopathy • Fetal hyperinsulinemia increases fat/glycogen deposit in cardiac muscle • Thickening interventricular septum • 30-50% IDM with hypertrophy on Echo • Obstructed left ventricular outflow • 5-10% symptomatic

23. Hypertrophic Cardiomyopathy

24. Hypertrophic Cardiomyopathy • Transient condition • Echo normalizes 6-12 months • Symptomatic infants recover after 2-3 weeks supportive care

25. Hypoglycemia • BG levels < 2.2 • Occurs within hours of birth • Increased risk with both LGA and SGA infants

26. Polycythemia • 13-33% IDM’s • Hct should be measured 12hrs after birth • Can lead to Hyperviscosity Syndrome • Renal vein thrombosis • Vascular sludging, ischemia, infarction of vital organs

27. Polycythemia

28. Hyperbilirubinemia • Associated with: • Poor maternal glycemic control • Polycythemia • Macrosomic infants • prematurity

29. Neurodevelopmental Outcome • Few studies available which adequately control confounders • Maternal ketones • Poorer psychomotor development • Elevated HbA1c levels during pregnancy • Poorer intellectual performance

30. Neurodevelopmental Outcomes • Developmental Delay • IUGR • Congenital malformations

31. Risk of Developing Diabetes • Type 1 DM: • Some genetic component: • Offspring – 6% • Siblings – 5% • Identical twins – 30% • (general population – 0.4%)

32. Risk of Developing Diabetes • Type 2 DM: • Much larger genetic component • Abnormal intrauterine metabolic environment • IDM – 45% • Prediabetic – 8.6% • Nondiabetic – 1.4%

33. Obesity • Increased BMI noted in offspring of diabetic mothers (ages 5-19 yrs) • Birth weight not indicative • Impaired Glucose Tolerance

34. Prepregnancy Counselling • Required to decrease complications in known diabetics: • Macrosomia: 63% (10%) • C-Section: 56% (20%) • Preterm delivery: 42% (12%) • Preeclampsia: 18% (6%) • Congenital Malformations: 5% (3%) • Perinatal Mortality: 3% (<1%)

35. Complete History/Physical Exam • Duration/Type of DM • Acute complications • Chronic complications • Glucose management • Physical activity • Medication • Obs/Gyne History

36. Laboratory Investigations • Urinalysis • Treat asymptomatic bacteriuria • Baseline renal function • Total protein, serum Cr, CrCl • Thyroid Function • TSH, Free T4

37. Comprehensive eye exam • Within 12 months prior to pregnancy • Within 1st trimester • Followed closely up to 1 year postpartum

38. Assessing Glycemic Control • HgbA1C: • mean blood glucose concentration over preceding 6 - 8 weeks • HgbA1A – In Pregnancy: • Mean BG concentration over 4 – 6 weeks • Life span of RBC shortened due to increased production

39. Hemoglobin A1C • Measured every 4-6 weeks • Goal < 6.1 prior to d/c contraception • Associated with lowest rate of adverse pregnancy outcome • Spontaneous abortion • Congenital malformation • Perinatal death

40. Assessing Glycemic Control • Glucose monitoring: • Pregnancy associated with exaggerated rebound from hypoglycemia • Urine Ketones: • Type 1 DM with illness or BG > 11.1 • DKA associated with high fetal mortality rate • Ketonemia may have adverse developmental effects.

41. Target Blood Glucose Values • Fasting glucose < 5.2 • 1 hr postprandial glucose < 7.7 • 2 hr postprandial glucose < 6.6 • Qhs < 5.9 • Strict glycemic control decreases adverse fetal outcomes

42. Hazards of Strict Glycemic Control • Hypoglycemia – • does not appear to be teratogenic in humans • Extremely strict control (BG < 4.8) can cause small-for-gestational age infants

43. Hazards of Strict Glycemic Control 2. Diabetic Retinopathy – • Related to degree of baseline retinopathy • Magnitude of reduction of chronic hyperglycemia • Mediated by closure of small retinal blood vessels that were narrowed but patent • Frequent retinal evaluation recommended in high risk women

44. Retinopathy • Comprehensive eye exam • Within 12 months prior to pregnancy • Within 1st trimester • Followed closely up to 1 year postpartum

45. Nutritional Therapy • Achieve euglycemia • Prevent ketosis • Provide adequate weight gain • Contribute to fetal well-being

46. Caloric Requirements • Increase 300 kcal/day in pregnancy • Based on BMI: • 30-40 kcal/kg/day – BMI < 22 • 30-35 kcal/kg/day – BMI 22-27 • 24 kcal/kg/day – BMI 27-29 • 12-15 kcal/kg/day – BMI > 30

47. Maternal obesity can cause: • Excessive fetal growth • Increase glucose tolerance Caloric restriction may be useful treatment

48. Oral Anti-hyperglycemic Agents • Sulfonylureas – • can cross the placenta causing fetal hyperinsulinemia: • Macrosomia • Neonatal hypoglycemia

49. Oral Anti-hyperglycemic Agents • Glyburide – • High protein binding so placental passage low • Several studies have not shown harmful effects

50. Oral Anti-Hyperglycemic Agents • Metformin and Thiazolindiones – • Minimal information available