Neonatal hypoglycemia: A little goes a long way☆,☆☆

Hepatic glucose production by glycogenolysis and gluconeogenesis is essential to maintain blood glucose levels, and the glucose-6-phosphatase system catalyses the terminal step of both pathways. Developmental delays in the postnatal up-regulation of hepatic glucose-6-phosphatase enzyme activity are common in preterm infants. Two groups of infants have been identified with failure of developmental regulation of glucose homeostasis. Firstly, up to 20% of preterm infants about to be discharged home are at risk of hypoglycaemia if a feed is delayed. Cortisol, corticotrophin and epinephrine levels are higher in the infants with severe and persistent hypoglycaemia, but insulin, glucagon and human growth hormone do not differ from normoglycaemic infants. Secondly, preterm infants with an inadequate glycaemic response to glucagon (30% at the time of discharge home) have relative fasting hyperglycaemia, hyperinsulinaemia, increased insulin:glucagon ratios and a lower insulin sensitivity index. Hormonal dysfunctions in preterm infants may contribute to failures in postnatal expression of hepatic enzymes.

While the fetus is completely dependent on his/her mother for glucose and other nutrient transfer across the placenta, the adult is completely independent, especially one who is neither pregnant nor diabetic. The neonate is considered to be in a transition between the complete dependence of the fetus and the complete independence of the adult. The heterogeneity that is the hallmark of neonatal glucose metabolism is illustrated by the observation that maintenance of euglycaemia in the sick and/or low-birthweight neonate is especially difficult. This reinforces the concept that the neonate is vulnerable to carbohydrate disequilibrium. In this discussion, we shall first evaluate the definition of euglycaemia by considering the ranges for hypo- and hyperglycaemia. We shall also review the considerable literature that has been published on measurement of the rate of glucose production and the rate of glucose utilization in the neonate. This review highlights where further work is necessary to understand the developing maturation (i.e. control) of glucose homeostasis in the neonate.

Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is the most common cause of recurrent hypoglycemia in neonates and infants. It is a disorder of glucose homeostasis characterized by unregulated hyperinsulinemia and profound hypoglycemia. PHHI may be differentiated from other causes of hypoglycemia by demonstrating the persistence of inappropriately high insulin levels regardless of blood glucose concentration. Prompt recognition and treatment of PHHI is critical because uncorrected hypoglycemia in the newborn period is associated with permanent damage to the central nervous system and subsequent mental retardation. The aim of therapy is to maintain euglycemia to protect the developing brain from possible damage. Despite recent advances in medical treatment, subtotal pancreatectomy is often necessary. This article will review the function of insulin, glucagon, and somatostatin, pathophysiology of hyperinsulinism, clinical manifestations, differential diagnosis, management, and reported neurologic outcomes of newborns and infants with PHHI.

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