To maintain normal cerebral function and development, a sufficient amount of metabolizable substrate must be supplied to the brain at all times. Glucose is the primary energy substrate for the growing fetus, newborn and adult brain under physiologic conditions. As much as 90% of all the energy consumed by the fetus is estimated to be derived from glucose. Plasma glucose concentration of the fetus changes with that of the mother, i.e. a linear relationship exists between the glucose concentrations of the mother and the fetus. At birth with umbilical cord clamping, the maternal supply of oxygen and nutrients ceases abruptly, which sets into motion the initiation of neonatal glucose production triggered by a surge in various circulating hormones. Most normal term and preterm infants are able to mobilize glycogen, initiate gluconeogenesis, and thereby produce glucose at 4–6 mg kg−1 min−1 in the immediate postnatal period. When glucose deficiency occurs, other organic non-glucose substrates are utilized to sustain the normal energy balance of supply and demand. This chapter will address normal cerebral glucose metabolism focusing on the delivery of glucose by a family of facilitative glucose transporters, the role of alternate substrates when glucose availability is limited, cerebral adaptive responses to hypoglycemia, and finally hypoglycemia-induced brain cellular apoptosis and/or necrosis.

Difficulties in defining hypoglycemia

Abnormalities in glucose homeostasis continue to pose problems in the term and preterm newborn infant. The reported incidence of hypoglycemia varies depending on the definition of hypoglycemia and the test employed to measure glucose concentrations.