Finding the best methods of screening newborns for persistent or genetic hypoglycemic disorders to reduce the risk of any permanent hypoglycemia induced brain injury was the focus of a recent review published online in the Journal of Pediatrics.

The issue is so important, according to lead author Charles A. Stanley, MD, with the Children’s Hospital of Philadelphia, a committee of the Pediatric Endocrine Society was recently formed to develop guidelines to evaluate and manage hypoglycemia in neonates, infants and children.

Drops in blood sugar levels in newborns is not a new discovery, as it’s well-documented that plasma glucose concentrations are lower in the first three days of life of normal newborn infants.

“Not until the 1960s was it appreciated that hypoglycemia in neonates could sometimes be symptomatic and, as in older infants and children, cause seizures or permanent brain damage,” Stanley and colleagues wrote.  “Although studies in laboratory animals have demonstrated postnatal developmental changes in specific enzymes involved in hepatic gluconeogenesis and ketogenesis it is unclear that such changes adequately explain transitional neonatal hypoglycemia in human newborns or if other mechanisms may be involved.”

For the review, Stanley and his fellow researchers, used the strategy currently employed by pediatric endocrinologists when evaluating hypoglycemia in older infants and children, which includes examining the major metabolic fuel and hormone responses to hypoglycemia in an effort to discover the mechanism of hypoglycemia and to make a diagnosis of the cause.

“We found that transitional neonatal hypoglycemia most closely resembles known genetic forms of congenital hyperinsulinism, which cause a lowering of the plasma glucose threshold for suppression of insulin secretion,” the authors wrote.  “This conclusion is based on strong evidence supported by 2 or more independent reports and provides a novel perspective on both the diagnosis and management of hypoglycemia in the first several days after birth.”

Stanley and team wrote that following birth, the mean plasma glucose concentrations in newborns drops by 25-30 mg/dL to a nadir of about 55-60 mg/dL.

“A representative example is the 1965 study by Cornblath et al, comparing glucose concentrations in normal weight and low birthweight newborn infants over the first 3 weeks of life.5 Immediately after birth, mean plasma glucose concentrations fell in the normal newborns to ∼60 mg/dL (3.3 mmol/L) at 2 hours (in this manuscript, whole blood glucose concentrations have been converted to equivalent plasma concentrations using a factor of 1.15),” the researchers wrote. “Glucose levels then rose steadily to stabilize at a mean plasma concentration greater than 80 mg/dL (4.4 mmol/L) by day of life 3.”

A second important feature of transitional neonatal hypoglycemia in infants is the concentration of plasma glucose are unaffected by the timing of the initial feeding or the interval between feedings.

The authors wrote that this pattern of the stable degree by which hypoglycemia cannot be readily explained by the developmental deficiencies in hepatic enzymes of glycogenolysis, gluconeogenesis, or ketogenesis identified in animal studies.

Three studies of transitional neonatal hypoglycemia to bring to light the underlying mechanisms of dropping blood sugar were conducted between 1974 and 1992.

“They all demonstrate that low glucose concentrations on the first day of life are associated with remarkably low concentrations of plasma ketones,” Stanley and team wrote.

The research team concluded that the most recent research found that transitional neonatal hypoglycemia in normal newborns is a hypoketotic form of hypoglycemia, caused by a lower blood sugar threshold for suppression of insulin secretion than would be normal for infants, children, or adults.

“We speculate that the reduced glucose threshold for suppression of beta-cell insulin secretion in the fetus and during a brief transitional period after birth may be due to immaturity in regulating beta cell gene expression (eg, the recently described expression of MCT1 and LDH or other “disallowed” genes in fetal beta cells),” they wrote. “The signals controlling this immature pattern of beta cell function remain unknown, but it is especially important to understand why fetal disorders, such as intrauterine growth restriction, birth asphyxia, maternal toxemia, and erythroblastosis fetalis cause a more severe and more prolonged form of immaturity in beta cell insulin regulation that sometimes requires further evaluation and treatment with diazoxide.”

Because differentiating an infant with normal blood sugar dips from one with a hypoglycemic disorder during the first day after birth is difficult, the authors note the Pediatric Endocrine Society guide for hypoglycemia in neonates recommends that the focus for the first 48 hours of life should be on stabilizing the infant’s glucose levels.

“Neonates whose glucose values remain low or who have other risk factors should be evaluated to determine the etiology of hypoglycemia and ensure their safety prior to discharge,” the authors advised.