Differential diagnosis and management of neonatal hypoglycemia

A remarkable series of coordinated metabolic adaptations occurs at birth. At the instant when the placental blood supply is curtailed, the fetus, hitherto largely dependent on maternal blood for its glucose, must initiate endogenous glucose production to meet its needs of approximately 5 to 8 mg/kg/min, mostly for cerebral use-a rate three to four times that of adults [1-3]. Several systems interact to accomplish this switch to endogenous glucose production. Within minutes of umbilical cord cutting, there is a three- to fivefold surge in glucagon and catecholamines, which initiate glycogen breakdown. High endogenous growth hormone and cortisol facilitate the onset of gluconeogenesis within several hours, and insulin secretion is blunted so that serum concentrations of insulin fall [1-3]. Enzymatic systems for glycogen breakdown and gluconeogenesis must be in place, along with a supply of substrate in the form of fat and amino acids [4-6]. The initiation of milk feeding also is important because it likely participates in the induction of ketogenesis, which spares glucose for brain consumption and facilitates gluconeogenesis [7]. Hypoglycemia represents not a single entity but a defect in one of these major adaptive pathways. Because these same pathways function to protect infants, children, and adults from hypoglycemia during fasting, hypoglycemia is more likely to occur during food deprivation (ie, fasting) [2,3]. Hypoglycemia in newborns is a relatively common and important disorder. It occurs frequently as a transient disorder, particularly in premature and small-for-gestational-age infants [2,3,5,6]. Hypoglycemia also may persist and reoccur and cause significant morbidity, including seizures and permanent brain injury [8,9]. The transient forms generally represent developmental immaturity in gluconeogenesis and ketogenesis and possibly depletion of glycogen stores by peripartum stress and secretion of catecholamines [10]. The persistent forms of neonatal hypoglycemia may reflect inborn errors of gluconeogenesis, ketogenesis, or glycogen breakdown. Hypopituitarism with defects in the adrenocorticotropic hormone (ACTH)-cortisol axis together with deficiency of growth hormone may produce relatively severe hypoglycemia in the newborn [2,3]. Persistent hyperinsulinism caused by congenital defects in the regulation of insulin, however, has emerged as the most common cause of persistent neonatal hypoglycemia in otherwise healthy infants [11]. This article uses the framework outlined above for a rational classification of neonatal hypoglycemia, which leads to systematic diagnosis and specific management.