Glucose is the major source of energy for tissue metabolism, particularly in the brain, where lack of alternate energy stores makes glucose an essential substrate. If there is a lower than normal glucose level in the blood, so that basic metabolic demands cannot be met, hypoglycemia results. A number of physiologic factors can leave the newborn particularly susceptible to hypoglycemia. Infants have an increased brain-to-body weight ratio, with a proportionately higher demand for glucose. In addition, newborns have an immature counter-regulatory response, which limits the use of alternate fuels, such as lactate and ketone bodies, in meeting basic metabolic requirements. Immediate consequences of hypoglycemia in the neonate include poor outcomes, worsening sepsis, and asphyxia. In the longterm, neonatal hypoglycemia may lead to impaired neurodevelopmental outcomes; some studies suggest that recurrent severe hypoglycemia may result in neuronal necrosis, contributing to impaired neurodevelopment.

Immediately after birth, the infant transitions from a maternal source of glucose to their own internal stores. Initially, the major source of neonatal glucose is from hepatic glycogen, via glycogenolysis. Within the first few hours of life, the neonate then develops the additional ability to maintain glucose levels via gluconeogenesis. Decreased stores, increased demands, or inadequate metabolic responses may disrupt the infant’s transition to independent glycemic control. Table 14.1 provides the common neonatal risk factors that may predispose the infant to hypoglycemia. Premature infants or small for gestational age (SGA) infants have decreased glycogen stores, putting them at risk for hypoglycemia. Septic infants, or infants with hypoxic-ischemic injuries, may have increased demands for glucose. If the infant is unable to meet these increased demands, hypoglycemia results. Infants of diabetic mothers (IDMs) frequently have islet-cell hypertrophy and higher than normal insulin levels. When transitioning from maternal glucose stores to their own stores, the insulin level may remain elevated, leading to hypoglycemia.