Handbook of Genetic Counseling/Diabetic Embryopathy

Diabetic Embryopathy

Etiology and natural history

• Diabetic embryopathy is a clinical diagnosis based on one or more congenital anomalies or fetal/neonatal complications in a baby that are attributed to his/her mother's diabetes
• Three main kinds of diabetes mellitus; if a mother has any of these three types, there is a significant risk for pregnancy complications and future health problems for mother and her offspring
  • Type I
    • Insulin dependent
    • Juvenile onset
    • Prone to ketosis
    • Body does not produce insulin because cells that produce insulin are attacked by immune system
    • Multifactorial causes, but those with family history are at higher risk
    • Tx: daily insulin injections
  • Type II
    • Non-insulin dependent
    • Adult onset
    • Not prone to ketosis
    • Body does not produce enough insulin or cells cannot use insulin properly
    • Inherited as an incompletely penetrating AR trait, but is definitely multifactorial
    • Tx: diet, exercise, and sometimes medication
  • Type III (Gestational diabetes)
    • Onset during pregnancy
    • Multifactorial causes, but those with family history of any diabetes are at higher risk
    • Tx: consistent monitoring of blood sugar level, diet and exercise; occasionally, insulin is required
    • Occurs in 1-4% of all pregnancies (higher in African American and Hispanic populations)
    • 20-50% of women who develop gestational diabetes will develop type II diabetes in the next 5-10 years.
• High blood sugar levels and ketones (substances that in large amounts are poisonous to the body) pass through the placenta to the baby, increasing the chance of birth defects
• When extra sugar is in a mother's blood during pregnancy, the baby is "fed" extra sugar, too, leading to a bigger baby that is harder to deliver
• It is not well-understood if the administration of insulin has teratogenic effects on the fetus; however, outcomes are definitely better when insulin is used to treat insulin-dependent maternal diabetes than when not

Clinical features

• All maternal and fetal features noted here are more severe and/or common when diabetic control is poor during pregnancy; nevertheless, even with good diabetic control, these features are observed
• Maternal morbidity factors in diabetic pregnancies which can increase a baby's risk for birth defects:
  • Ketoacidosis
  • Polyhydramnios
  • Preeclampsia/chronic hypertension
  • Preterm labor
  • Cesarean section
• Fetal complications and birth defects associated with maternal diabetes
  • Cardiac anomalies: most commonly VSD or TGV
  • DiGeorge anomaly: due to abnormal neural crest cell migration; affects normal fetal development of the heart, thymus, and parathyroid glands
  • NTD's: thought to be due to maternal diabetic factors causing improper embryonic folding; most commonly spina bifida and anencephaly
  • Macrosomia: occurs in ~ 1/3 of all diabetic pregnancies; can cause life-long obesity for child
  • IUGR: thought to be due to nutrient limitation associated with maternal hypertension.
  • SAB: debated somewhat, but appears to be increased in pregnancies with poor diabetic control
  • Caudal regression: agenesis of sacrum and lumbar spine, hypoplasia of lower extremities; thought to be due to improper embryonic folding caused by maternal diabetic factors
  • Abnormal postnatal neurologic development: thought to be due to effects of ketosis
• Perinatal and neonatal complications associated with maternal diabetes
  • Fetal asphyxia: can cause cerebral palsy as well as affecting many other systems such as pulmonary, GI, and cardiovascular
  • Preterm birth: can lead to respiratory distress syndrome; occurs in ~ 30% of diabetic pregnancies, even when diabetic control has been meticulous
  • Hypoglycemia: can cause seizures, coma, and brain damage if not recognized and treated quickly
  • Hypocalcemia and hypomagnesemia: thought to be caused primarily by premature birth and its affects on parathyroid function
  • Hyperbilirubinemia: thought to be caused primarily by premature birth
  • Cardiomyopathy and/or cardiomegaly: most commonly seen in macrosomic infants of poorly controlled diabetic mothers

Surveillance and Treatment

• Preconceptionally
  • Counseling recommended for all women with overt diabetes or a history of gestational diabetes
  • Severity of woman's disease should be considered
  • Woman should be apprised of possible complications to herself and her child
• During pregnancy
  • Should be handled by a team of healthcare workers including: perinatologist, endocrinologist, dietician, and social worker
  • Patient should be seen every 4-8 weeks, and should be considered "high risk"
  • Mother should be closely monitored for diabetic control so that adjustments can be made for insulin, diet, and exercise
    • Insulin therapy can be altered in many ways, including continuous subcutaneous infusion if necessary
    • Must be careful to not over-insulinize mother and cause hypoglycemia
  • Surveillance for health risks to mother should be closely monitored, including: cardiovascular health, renal function, blood pressure, weight gain
  • Maternal serum screening should be done at 16 weeks
  • Fetus should be monitored regularly via level II ultrasound for detection of macrosomia, IUGR, cardiac anomalies, NTDs, and any other associated conditions
• At birth
  • Delaying delivery until term is often contraindicated when baby is macrosomic or when mother is preeclampsic
  • Cesarean section rate is about 30-50% in diabetic pregnancies
  • Delivery should occur at facility prepared to deal with fetal and maternal complications associated with diabetic pregnancy
• Postpartum management
  • Infant should be closely monitored for associated conditions; EKG and serum tests should be run
  • Mother's insulin should be closely monitored; many women need less insulin directly following delivery

Psychosocial issues

• Guilt on mother's part for risks and complications to her baby
• Anxiety about own health due to having a high risk pregnancy
• Financial concerns over costly prenatal and postnatal care
• Fear about possible outcomes of pregnancy

Sources

• Creasy, RK and Resnik, R. 1994. Maternal-Fetal Medicine : Principles and Practice, 3rd ed. Ch. 54 : "Diabetes in pregnancy" (p.934-978). W.B. Saunders Company : Philadelphia.
• American Diabetes Association Homepage-http://www.diabetes.org
• Larsen, W.J. 2001. Human Embryology, 3rd ed. Churchill Livingstone : New York.

Notes

The information in this outline was last updated in 2003.