50 Years Ago in The Journal of Pediatrics: The Incidence of Neonatal Hypoglycemia in a Nursery for Premature Infants

Abstract

Wybregt et al made important contributions to the burgeoning field of hypoglycemia in premature neonates. They published one of the first systematic studies documenting the demographics and high prevalence of hypoglycemia in preterm newborns, defined arbitrarily as glucose concentrations less than 30 mg/dl. They noted increased incidence in small for gestational age (SGA) infants, a description that was just being adopted in research and clinical practice. They also found that no single clinical sign could reliably distinguish the hypoglycemic infant. The last 50 years have produced several more observational studies on hypoglycemia in this population and progress has been made in understanding the pathophysiology of preterm neonatal hypoglycemia. However, we are not much closer today to understanding the long term neurodevelopmental consequences of hypoglycemia for these patients, and at what glucose concentration to become concerned. In 1988, Lucas et al published another observational study of glucose concentrations in preterm infants (less than 1850 grams).1 Mirroring the Wybregt study, they found a high incidence of arbitrarily defined hypoglycemia, especially for SGA newborns. In addition, frequent glucose levels below 45mg/dl were associated with worse neurodevelopment at eighteen months. Tin et al2 replicated the study in 2012 and did not find an association between frequency of low glucose concentrations and worse neurodevelopment at two and fifteen years of age. Both studies, like the Wybregt study, agreed that clinical signs are neither sensitive nor specific. Today, most people agree that low glucose concentrations are common in preterm newborns, more common in SGA newborns, and that most clinical signs are not diagnostic of hypoglycemia without laboratory confirmation of a low glucose concentration. But the long term consequence and optimal treatment, especially for asymptomatic low glucose concentrations, are still debated. Today, there are many open areas for research into understanding what defines pathologic hypoglycemia, as well as its long term consequences.3 Continuous glucose monitoring shows promise as a way to more accurately measure a patient’s glucose concentrations. Combined with rigorously obtained long term outcome data, a better understanding of the exact mechanisms of preterm hypoglycemic brain injury, and research into new techniques to monitor for ongoing damage in real time, such as functional imaging, innovative electroencephalographic techniques, or novel serum biomarkers, progress will be made.