# 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.