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.