Hypoglycemia is common during the first few days of life, with estimates of prevalence ranging from one in 10 babies to one in three, and perhaps as high as 50% in certain high-risk populations. The American Academy of Pediatrics and the Pediatric Endocrine Society have different definitions for neonatal hypoglycemia and different treatment recommendations. And while there are strong associations between neonatal hypoglycemia and neurodevelopmental deficits, cause and effect remain elusive.

“We know neonatal hypoglycemia is more common in four groups of babies: preterm, small for gestation, large for gestation, and those born to mothers with diabetes,” said Raghavendra Rao, MD, Professor and Director of Neonatology at the University of Minnesota and the Center for Neurobehavioral Development. “There is also the factor of maternal obesity, even if the mother does not have diabetes. And all of these populations are increasing.”

Dr. Rao will be joined by three other expert presenters during the Scientific Sessions symposium Neonatal Hypoglycemia—Overdiagnosed or Underestimated? The two-hour session begins at 2:15 p.m. ET Monday, June 28.

Based on animal models, it appears that newborn brains can tolerate about four hours of hypoglycemia before beginning to show the effects of energy failure, Dr. Rao said. Most babies appear to bounce back from a single short episode of hypoglycemia without evident detriments, he added, but the situation is different with recurrent episodes and rapid treatment may actually worsen outcomes.

Why neonatal hypoglycemia occurs is less clear. The threshold for turning off insulin secretion in the fetus is lower than after birth, explained Charles Stanley, MD, Founder of the Congenital Hyperinsulinism Center at Children’s Hospital of Philadelphia and Professor Emeritus of Pediatrics at the University of Pennsylvania Perelman School of Medicine. Blood glucose in the fetus is largely controlled by the mother.

“The function of insulin production by the fetus is not to control blood sugar levels but to maintain fetal growth,” he said. “Fetal hyperinsulinism is an adaptation that extends into the first day or two after birth. For 99.9% of newborns, this transitional period of mild low blood sugar is not a problem. I’m focusing on that 0.1% of babies with persistent hypoglycemia due to perinatal stress or genetic forms of hyperinsulinism for whom it is a serious problem that can result in seizures and permanent brain damage.”

Knowing the molecular mechanisms of insulin secretion that cause transitional hypoglycemia in newborns could help characterize the mechanisms by which beta cells regulate insulin secretion in normal individuals, Dr. Stanley continued. These pathways can be exacerbated by hypoxia and exposure to hyperglycemia in mothers with diabetes, leading to persistent hypoglycemia in their babies.

Epidemiological data suggest that maternal metabolism can have a significant impact on neonatal hypoglycemia. The growing population of mothers entering pregnancy who are older, have preexisting metabolic dysfunction, and have diabetes is focusing attention on ways to evaluate newborns for possible hypoglycemia and to minimize lasting effects.

“Current clinical dilemmas include who to screen, what definition of hypoglycemia is linked with long-term developmental sequelae, and how to treat hypoglycemia,” said Sarbattama Sen, MD, Assistant Professor of Pediatrics at Harvard Medical School. “In addition to hypoglycemia, there are some interesting early data that rapid fluxes in glucose levels may also be harmful in the long term. We desperately need studies designed to inform clinical practices and policies.”

New primary data are starting to emerge, fueled in part by continuous glucose monitoring and more accurate glucometers coming into wider use in neonatal intensive care units.

“About 25% to 30% of all newborns will have a low blood sugar, and most of them are just normal babies,” said Paul Rozance, MD, Professor of Pediatrics and Neonatology at the University of Colorado School of Medicine. “The trick is being able to distinguish who’s normal from who might be having a pathological low glucose concentration and whether that low glucose results in a bad outcome. Just figuring out what matters in neonatal hypoglycemia is still the major question.”