1. Infants of Diabetic Mothers
Jennifer Bromley
Newborn Nursery Presentation

2. Introduction Diabetes = most common medical complication 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
Gestational = glucose intolerance that appears during pregnancy
pregestational: 35% type 1, 65% type 2
Prenatal, neonatal and even further reaching complications to the fetus

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
Treatment goals fasting glucose <90, 1h postprandial <120
Women with GDM higher risk for developing preeclampsia, due, in part, to insulin resistance
Higher risk of stillbirth: fetuses of women with GDM are at higher risk of IUFD, mostly related to poor glycemic control, and higher risk for patients requiring medical interventions above just diet control.

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
Study in which amniotic fluid insulin concentrations in women with type 1 DM were higher with macrosomic fetuses than with those appropriate for gestational age.
Another study demonstrated increased levels of C-peptide in cord blood samples of infants with mothers who were diabetic compared to control infants of nondiabetic mothers; Elevated cord blood c-peptide levels were associated with neonatal hypoglycemia and macrosomia but not hyaline membrane disease.

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 causes disproportionally increased abdominal circumference due to fat deposition and visceromegaly, while the head growth remains normal
Excessive nutrients because mom’s DM is poorly controlled

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 and gestational DM
Congenital malformations account for 50% of perinatal deaths to diabetic mothers
Risk of perinatal death can be significantly reduced by good glycemic control during pregnancy

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: transient inability to pass meconium that resolves spontaneously
Unique to infants of diabetic mothers
Caudal regression syndrome 200x more common in infants of diabetic mothers
Caudal regression syndrome aka caudal agenesis, sacral dysgenesis, caudal dysplasia sequence

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 with excessive fat accumulation in the abdominal and scapular regions and visceromegaly
Occurrence is 4 times higher in infants born to diabetic 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
Transient tachypnea of the newborn: aka retained fetal lung fluid; occurs 2-3 times more commonly in IDMs than normal infants; may be related to decreased fluid clearance in the diabetic fetal lung although frequent cesarean delivery is a contributing factor as well

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 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
HYPOGLYCEMIA:
Tight glucose control does not eliminate this risk – still 14% of infants were hypoglycemic in mothers who had tight glycemic control during pregnancy.
Even premature or SGA infants of diabetic moms are at risk: glycogen stores are decreased and hyperinsulinemia decreases the ability to mobilize hepatic glycogen
Potentiating factor is depressed response to hypoglycemia of counter regulatory hormones (glucagon and catecholamines)
HYPOCALCEMIA
Usually asymptomatic and resolves without treatment so routine screening is not recommended
BUT worry about infants with jitteriness, lethargy, apnea, tachypnea, seizures
Hypomagnesemia: usually asx and not usually treated; hypomageneemia can decrease both PTH secretion and PTH responsiveness so if the baby has BOTH hypoCa and hypoMg, the Ca may not correct until the Mg is corrected

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
Polycythemia  hyperviscosity syndrome including vascular sludging, ischemia, and infarction of vital organs (increased risk of renal vein thrombosis)

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
Head circumference at 3 years old negatively correlated with HbA1c during pregnancy
Smaller head circumference associated with poorer intellectual performance
Psychomotor development at six to nine years of age correlated with maternal ketone concentrations during the second and third trimesters
IUGR and malformations also contribute to developmental Delay

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
Intrauterine exposure to hyperglycemia and hyperinsulinemia may affect the development of adipose tissue and pancreatic beta cells, leading to future obesity and altered glucose metabolism
A number of studies have found that wile macrosomia may resolve within the first year of life, obesity reoccurs in childhood at increased rates in children of diabetic mothers

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.