Review Question - QID 108655

This infant is large for gestational age, has poor feeding and hypothermia, and seizes, making the mostly likely diagnosis hypoglycemia. As the infant of a diabetic mother with poor glucose control throughout pregnancy, the most likely etiology for his hypoglycemia is transplacental hyperglycemia and resultant ß-cell hyperplasia.

Whether type I, type II, or gestational, maternal diabetes can cause a number of adverse outcomes in the infant. Most serious are the congenital anomalies such as transposition of the great arteries, spina bifida, craniofacial malformations, small left colon syndrome, and caudal regression syndrome (Illustration A). Aside from these anomalies, poor glycemic control in the mother (fasting glucose greater than 95 mg/dL and postprandial glucose greater than 140 mg/dL) can cause hypoglycemia in the infant due to glucose crossing the placenta and triggering ß-cell hyperplasia and hyperinsulinemia in the fetus. The effect of insulin persists just after birth, resulting in hypoglycemia that can present as hypothermia, tachypnea, lethargy, poor feeding, jitteriness, and ultimately seizures. Causes include a diabetic mother, sepsis, and inborn error of metabolism. A postprandial fingerstick glucose less than 50 mg/dL in a symptomatic infant should prompt immediate replacement with continuous intravenous dextrose. Glucagon may be used if hypoglycemia is persistently severe and symptomatic. Prolonged hypoglycemia can result in brain injury and developmental delay.

Illustration A shows a radiograph of caudal regression syndrome or sacral agenesis. There is congenital absence of the lumbosacral vertebrae, sacrum, and several caudal ribs.

Incorrect Answers:
Answer 1: Transplacental action of maternal insulin is minimal, as insulin cannot cross the placenta. Although maternal hyperinsulinemia does result from type II diabetes and gestational diabetes, this is not the mechanism by which fetal hyperinsulinemia occurs.

Answer 3: Neonatal sepsis in the first day of life is most commonly due to maternal chorioamnionitis (polymicrobial), group B Streptococcus colonization (GBS), and Escherichia coli. Though this neonate’s mother did have GBS on routine culture, she never ruptured her membranes and thus did not require prophylaxis with intravenous penicillin. In addition, although neonatal sepsis can cause seizures, tachypnea, and poor tone, term infants are generally febrile (as opposed to hypothermic like this patient) and tachycardic (whereas this patient is not). Sepsis should certainly be on the differential due to the need for urgent treatment with empiric ampicillin and gentamicin, but it is not the most likely cause of this infant’s presentation.

Answer 4: Inborn errors of metabolism include conditions such as galactosemia, hereditary fructose intolerance, carbamoyl phosphate synthetase I deficiency, and phenylketonuria. These can all present after hours to days with poor feeding, hypoglycemia, and seizures, but it is exceedingly rare for them to cause symptoms after only one hour of life. Furthermore, feeding is often a precipitant for symptoms, while this infant’s symptoms preceded his first feeding. All newborns are screened for the most common metabolic deficiencies, and treatment is specific to each condition.

Answer 5: Neonatal encephalopathy (NE) is characterized by central nervous system dysfunction such as altered consciousness, seizures, poor tone, and feeding difficulties. Some of these symptoms are seen in this neonate, but there is not a reasonable etiology for why he would have NE. Risk factors for NE include intrauterine growth restriction (whereas this infant is large for gestational age), placental pathologies such as chronic abruption, intrapartum hypoxia ischemic brain injury with nonreassuring fetal heart rate tracing, and low Apgar scores. Workup should include neuroimaging and evaluation for global hypoxia (oliguria, elevated liver enzymes, etc.). Therapeutic hypothermia is the treatment of choice.

Bullet Summary:
In poorly managed maternal diabetes, persistent maternal hyperglycemia can cause fetal hyperglycemia and ß-cell hyperplasia. In the newborn, this may present with hypoglycemia, poor feeding, and seizures, and treatment includes aggressive intravenous dextrose therapy.