Infants of Diabetic Mothers

1. Infants of Diabetic Mothers Jennifer Bromley Newborn Nursery Presentation 3.25.2011

2. Introduction • Diabetes = most common medicalcomplication of pregnancy • 4% of pregnant women in the US • 88% gestational • 12% pregestational • Prenatal complications: • Preeclampsia • Prematurity • Stillbirth • Congenital anomalies • LGA/macrosomia • Neonatal complications: • Hypoglycemia • Hyperbilirubinemeia • Hypocalcemia • Polycythemia • RDS • Longer-term outcomes

3. Prenatal Management • Treatment: self-glucose monitoring, diet + exercise, insulin, oral anti-hyperglycemic agents • Antenatal testing: twice weekly non-stress tests with amniotic fluid index starting at 32 weeks gestation • Single third trimester ultrasound to screen for macrosomia • Scheduled C/S if the estimated fetal weight > 4500g • Elective induction of labor… • …for medically controlled GDM at 39 weeks • …for diet controlled GDM at 40 weeks • Lower rates of macrosomia and LGA infants • Lower rates of shoulder dystocia • Lower C/S rates

4. Diabetic Embryopathy • Hyperglycemia in the 6-7 weeks of gestation • Yolk sac failure  • Spontaneous abortions • Major fetal malformations • Other teratogens may also be linked to hyperglycemia including ketones, and reduced levels of arachidonic acid with overproduction of oxygen radicals that leaves to abnormalities in prostaglandin metabolism • Disrupting the vascularization of developing tissues

5. Diabetic Fetopathy • Intermittent maternal hyperglycemia  Fetal hyperglycemia  Premature maturation of fetal pancreatic islets Hypertrophy of beta cells Hyperinsulinemia • Fetal hyperinsulinemia  Stimulates glycogen storage in the liver Increased activity of hepatic enzymes of lipid synthesis “Fatty liver” • Increased hepatic enzymes for lipid synthesis  Elevated metabolic rate  Increased oxygen demand  Fetal hypoxemia

6. Fetal Growth • Excessive nutrients  Increased fetal growth(particularly of insulin-sensitive tissues – liver, muscle, cardiac muscle, subQ fat)and macrosomia • After 24 weeks gestation,hyperglycemia causesdisproportionally increasedabdominal circumferencedue to fat deposition andvisceromegaly, while thehead growth remainsnormal

7. Neonatal Effects • Congenital anomalies • Prematurity • Perinatal asphyxia • Respiratory Distress Syndrome • Metabolic

8. Neonatal Effects: Congenital Anomalies • A large case-control study showed the relative risk for major malformations in infants of mothers with type 1 DM versus the risk in infants of nondiabetic mothers: 7.9 • Another case-control study showed increased prevalence of birth defects in infants of mothers with pregestational andgestational DM • Congenitalmalformationsaccount for 50% ofperinatal deaths todiabetic mothers

9. Neonatal Effects: Congenital Anomalies • 2/3 of the anomalies involve cardiac or CNS • Anencephaly and spina bifida occur 13-20x more frequently in infants of diabetic mothers • GU, GI, and skeletal anomalies also occur at increased rates • Small left colon syndrome: transientinability to pass meconium that resolvesspontaneously • Unique to infants of diabetic mothers • Caudal regression syndrome 200x more commonin infants of diabetic mothers

10. Neonatal Effects: Premature Delivery • Spontaneous premature labor occurs more frequently in diabetic pregnancies • Poor glycemic control is associated with a high rate of UTIs • Maternal preeclampsia, which also occurs more commonly in diabetic pregnancies, also contributes to premature delivery

11. Neonatal Effects: Perinatal Asphyxia • Increased risk of… • fetal heart rate abnormalities during labor • Low Apgar scores • Intrauterine death • As many as 27% of infants born to diabetic mothers had perinatal asphyxia • Hypothesis: maternal vascular disease, manifested by nephropathy, contributes to fetal hypoxia and subsequent perinatal asphyxia

12. Neonatal Effects: Macrosomia • Macrosomia = birth weight > 4000g • More likely to have hyperbilirubinemia,hypoglycemia, acidosis, respiratory distress,shoulder dystocia, and brachial plexus injuries • Infants usually appear large and plethoric withexcessive fat accumulation in the abdominal andscapular regions and visceromegaly • Occurrence is 4 times higher in infants born todiabetic mothers • Other end of the spectrum: mothers with vasculopathy causing intrauterine growth restriction

13. Neonatal Effects: Respiratory Distress Syndrome • Hypothesis: hyperinsulinemia may cause delayed maturation of surfactant synthesis by interfering with the glucocorticoids normally responsible for induction of lung maturation • To ensure lung maturity, can preform an amniocentesis and look at the lechitin to sphingomyelin ratio which is >2 in mature lungs • DDX of respiratory distress in infants of diabetic mothers: pneumonia, hypertrophic cardiomyopathy, transient tachypnea of the newborn • In contrast, fetal lung maturation may occur early in diabetic pregnancies complicated by vasculopathy

14. Neonatal Effects: Metabolic • Hypoglycemia • Blood glucose <40 mg/dL • Occurs in as many as 1/3 of all infants of diabetic mothers • Within the first few hours after birth • Hyperinsulinemic state typically lasts 2-4 days • Hypocalcemia • Total calcium < 7 mg/dL or ionized calcium < 4 mg/dL • Occurs in 10-50% of infants of diabetic mothers • Usually bottoms out between 24-72 hours after birth • Higher serum ionized Ca++ in utero can suppress fetal parathyroid glands • Hypomagnesemia • Magnesium < 1.5 mg/dL • Occurs in 40% of infants of diabetic mothers in the first 3 days of life • Maternal hypomagnesimia caused by increased urinary loss secondary to diabetes • Fix Mg before you can fix Ca

15. Neonatal Effects: Other Complications • Polycythemia and hyperviscosity syndrome • 13-33% of infants of diabetic mothers • Chronic fetal hypoxemia  increased erythropoietin • Hyperbilirubinemia • 11-29% of infants of diabetic mothers • Increased hemolysis secondary to glycosylation of erythrocyte membranes • Hypertrophic cardiomyopathy • Transient, resolves as insulin concentrations normalize

16. Neurodevelopmental Outcome • Poorly controlled diabetes may result in developmental abnormalities • Studies of 3 and 6-9 year olds have showed cognitive and developmental differences between children of diabetic mothers and their peers

17. Long-term Metabolic Risk • Inheritance of pregestational diabetes is genetically linked • Children of diabetic mothers are more likely to be diabetic and more likely to be obese

18. Conclusion • Tight maternal glycemic control is associated with improved outcomes in infants of diabetic mothers • Regardless of glycemic control, these infants are at higher risks for birth defects, abnormal growth, metabolic complications and even neurodevelopmental delay as compared to their peers of non-diabetic mothers.