A 2-hour-old newborn has a blood glucose concentration of 30 mg/dL. The patient was delivered via caesarean to a 32-year-old woman at 38 weeks gestation. Birth weight is 4.5 kg (9 lb 14 oz). The pregnancy was complicated by gestational diabetes treated with insulin. However, glycemic control remained suboptimal due to maternal noncompliance with insulin treatment and poor adherence to dietary recommendations. Examination of the neonate is unremarkable. Which of the following is the most likely primary mechanism responsible for this patient's low blood glucose concentration?
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Glucose levels fall in all newborns after birth, but usually remain ≥40 mg/dL due to mobilization of hepatic glycogen stores and initiation of feeding; glucose <40 mg/dL is indicative of neonatal hypoglycemia, a common metabolic derangement seen in infants of diabetic mothers.
During gestation, glucose is transferred continuously from mother to fetus via the placenta. Mothers with diabetes, particularly those with poor glycemic control, often have hyperglycemia, causing fetal hyperglycemia. In utero, this results in compensatory hyperfunctioning of pancreatic beta cells, which then produce increased amounts of insulin to handle the excessive glucose load. Once the maternal glucose supply is interrupted at delivery, persistent hyperinsulinemia causes increased glucose consumption and transient neonatal hypoglycemia.
Most neonates with hypoglycemia are asymptomatic but may develop autonomic symptoms (eg, jitteriness, irritability) and, if severe, hypotonia and seizures. Macrosomia (>4 kg [8 lb 14 oz] birth weight) is also common in infants of diabetic mothers due to increased exposure to growth factors (eg, insulin, insulin-like growth factors, growth hormone) that stimulate fetal growth and increased deposition of glycogen and fat in developing tissues (Choice A).
(Choice C) Hypoglycemia due to impaired hepatic glycogenolysis is characteristic of certain glycogen storage diseases (eg, von Gierke disease, Cori disease), which typically present within the first several months of life with failure to thrive, ketotic hypoglycemia, and hepatomegaly (ie, protruding abdomen) due to increased hepatic glycogen content.
(Choices D and E) Critically ill infants may produce increased cortisol due to stress (eg, sepsis, mechanical ventilation) with resultant hyperglycemia. Insulin resistance, which is not typically seen in infants but is related to obesity in children and adults, also causes hyperglycemia. However, this neonate is hypoglycemic.
Educational objective:
Neonatal hypoglycemia is common in infants of diabetic mothers. The pathophysiology involves maternal hyperglycemia, which in turn causes fetal hyperglycemia and compensatory hyperfunctioning of the pancreas (ie, hyperinsulinemia). After birth, persistently elevated insulin levels lead to transient hypoglycemia.