Chapter 45: Hypoglycemia in the Newborn

INTRODUCTION

This chapter outlines the epidemiology, etiology, pathophysiology, differential diagnosis, and management approach to the neonate with hypoglycemia, here defined as 40 mg/dL or less (≤2.2 mmol, the fifth percentile for age) during the first 2 days of life and 50 mg/dL or less (≤2.8 mmol) of whole blood glucose thereafter, with or without suggestive symptoms. Note that plasma glucose concentration is about 10%–15% greater than whole blood glucose concentration, so criteria for hypoglycemia based on plasma glucose measurements must be appropriately adjusted to be greater. Recent advances in our understanding of the biochemistry, physiology, and molecular biology regulating prenatal and postnatal glucose homeostasis combine to provide a rational basis for defining, identifying, diagnosing, and treating hypoglycemia in the newborn to enable normal neurodevelopment.^{1, 2} These considerations provide a systematic approach to the problem of neonatal hypoglycemia and argue for glucose measurements to become part of routine care in all neonates prior to discharge from the newborn nursery and in all sick neonates even after discharge from the newborn nursery.

EPIDEMIOLOGY

Hypoglycemia is a relatively common and highly important problem in the newborn.^{3, 4, and 5} Precise data on incidence are unavailable and depend in part on the definition of hypoglycemia, an area of ongoing discussion, as well as the degree of gestational maturity and condition of the newborn.^{1, 2, and 3} Based on a meta-analysis,⁵ it has been proposed that, in full-term normal newborns, blood glucose of 40 mg/dL or less in the first 48 hours and 48 mg/dL or less between 48 and 72 hours represents less than the fifth percentile for age. A minor modification to these data permits defining hypoglycemia as 40 mg/dL or less in the first 2 days of life and 50 mg/dL or less thereafter. By the fourth day of life, normal infants usually maintain average blood glucose values greater than 60 mg/dL, approaching values of healthy children and adults. Using these criteria, the reported incidence of hypoglycemia in the first days of life varies from approximately 70% in infants who are small for gestational age (SGA),⁶ 20%–50% in those large for gestational age (LGA) but otherwise-normal newborn infants born to nondiabetic mothers, and greater than 50% in those born to infants of diabetic mothers⁷; only about 2% of term infants born to nondiabetic mothers after normal pregnancy develop hypoglycemia.⁸

The importance of neonatal hypoglycemia lies in its association with potential impairment of neurocognitive development⁶ because glucose is the preferential energy substrate of the newborn's brain, which normally utilizes greater than 90% of normal basal glucose turnover and has been shown to be about 4–8 mg/kg/min.⁹ Although the brain of a neonate can use other energy substrates, such as lactate and β-hydroxybutyrate, in hypoglycemia secondary to hyperinsulinism (HI), the production of glucose (by glycogenolysis or gluconeogenesis) is suppressed, as ...