Current perspectives on neonatal hypoglycemia, its management, and cerebral injury risk

Abstract

Glucose is an essential substrate for mammalian cells; in particular, the brain needs glucose continuously as a primary source of energy. Hypoglycemia is the most common biochemical finding in the neonatal period. However, despite the common occurrence, there is still controversy on the definition of hypoglycemia in the newborn period. This has led to the development of guidelines designed to identify infants "at-risk" and the implementation of an "operational threshold" for physicians to consider intervention. In healthy term infants, the optimal hormonal and metabolic adaptations during the immediate neonatal period ensure an adequate energy substrate for the vital organs, whereas the abnormal glucose homeostasis observed in preterm and growth-retarded infants is multifactorial in origin. For these high-risk infants, it is important to identify, screen, and prevent significant hypoglycemia. Detailed investigations are warranted in infants with severe and persistent hypoglycemia. Neonatal hypo-glycemia is a major cause of brain injury. The speculated mechanisms of cellular injury include excitatory neurotoxins active at N-methyl-D-aspartate receptors, increased mitochondrial free radical generation with initiation of apoptosis and altered cerebral energetic characteristics. This hypoglycemic brain injury predominantly affects parieto-occipital regions causing cognitive, sensory, psychomotor, and behavioral deficits in children. This state of the art review article covers the fetal-neonatal metabolic adaptation, glucose homeostasis in normal and abnormal conditions, management strategies, and late neurological sequelae of hypoglycemia. Perinatal glucose physiology Fetal blood glucose regulation During fetal life, glucose is the principal energy substrate. Throughout pregnancy, the fetus receives a supply of substrates essential for growth and for the deposition of fuel stores required after birth through the placental circulation from the mother. Amino acids and lactate in addition to glucose function as energy stores in the fetus. 1 Glucose contributes nearly 65% of the total energy requirement of the fetus and the rest is contributed predominantly by lactate. 1 Maternal hepatic glucose production increases by 16%-30% through gestation to supply the fetus with energy. 2 By facilitated diffusion, glucose is transported across the placenta, but the fetus is capable of endogenous glucose production in the face of placental insufficiency. 1 The placenta transfers to the fetus only 40%-50% of the maternal glucose it receives and converts nearly 60% of the glucose transferred from the maternal circulation to lactate, which is delivered to the fetus and mother in a ratio of 1:3. 3 The fetus receives high amounts of amino acids through the placenta leading to higher fetal amino