1. Diabetes & Pregnancy By: 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. Impaired Glucose Tolerance
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 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

51. Recommendations Oral anti-hyperglycemics not recommended in pregnancy
Some question as to usage in non-compliant patients on individualized basis
Insulin - patients unable to obtain euglycemia through diet alone

52. Insulin Therapy Type 2 DM: Insulin during preconception period
Obtain adequate HgbA1C
Avoid excessive weight gain
Moderate low-impact exercise

53. Insulin Therapy Rapid Acting Insulin (Lispro/Aspart)
Acceptable safety profiles
Minimal transfer across the placenta
No evidence teratogenesis
Note: Compared to Regular Insulin
Improves postprandial BG
Decreases risk hypoglycemia

54. Insulin Therapy Longer Acting Insulin: NPH recommended Glargine:
high affinity for IGF-1 receptor
Risk of macrosmia

55. Intrapartum Management
Latent phase – insulin to maintain BG
Active Phase – insulin resistance rapidly decreases
BG check hourly
Avoid boluses of glucose
Increases risk of neonatal hypoglycemia
Fetal hypoxia
Fetal/neonatal acidosis

56. Postpartum Management
Postpartum - insulin requirements drop sharply
Short ½ lives of placental growth hormone and placental lactogen
Insulin doses readjusted hrs
Note: Breast-feeding patients should remain on insulin

57. The End!