Hypoglycemia in the preterm neonate: etiopathogenesis, diagnosis, management and long-term outcomes

Abstract

Glucose, like oxygen, is of fundamental importance for any living being and it is the major energy source for the fetus and the neonate during gestation. The placenta ensures a steady supply of glucose to the fetus, while birth marks a sudden change in substrate delivery and a major change in metabolism. Hypoglycemia is one of the most common pathologies encountered in the neonatal intensive care unit and affects a wide range of neonates. Preterm, small for gestational age (GA) and intra-uterine growth restricted neonates are especially vulnerable due to their lack of metabolic reserves and associated co-morbidities. Nearly 30-60% of these high-risk infants are hypoglycemic and require immediate intervention. Preterm neonates are uniquely predisposed to developing hypoglycemia and its associated complications due to their limited glycogen and fat stores, inability to generate new glucose using gluconeogenesis pathways, have higher metabolic demands due to a relatively larger brain size, and are unable to mount a counter-regulatory response to hypoglycemia. In this review we will discuss the epidemiology; pathophysiology; clinical presentation; management and neurodevelopmental outcomes in affected infants and summarize evidence to develop a rational and scientific approach to this common problem.

Keywords: Hypoglycemia; gluconeogenesis; hypoglycemic brain injury; intra-uterine growth restriction; neurodevelopmental outcome.

Figure 1

Mechanisms which generate acetyl CoA, the metabolic common currency which determines ATP levels and clinical presentation. ATP, adenosine triphosphate.

Figure 2

Molecular machinery which controls Insulin secretion by the pancreatic β cells.

Figure 3

Suggested algorithm for management of hypoglycemia in the preterm infant.