Re-evaluating "transitional neonatal hypoglycemia": mechanism and implications for management.

From the Division of Endocrinology, Children’s Hospital of Philadelphia, Philadelphia, PA; Division of Neonatology, University of Colorado School of Medicine, Aurora, CO; Department of Endocrinology, Cook Children’s Medical Center, Fort Worth, TX; Newborn Intensive Care Unit, Waikato Hospital, Hamilton, New Zealand; Texas Children’s Hospital, Houston, TX; Department of Endocrinology, Great Ormond Street Hospital for Children, London, United Kingdom; Division of Endocrinology, Massachusetts General Hospital, Boston, MA; Division of Preventive Medicine, Mayo Clinic, Rochester, MN; Division of Neonatology, Children’s Hospital of Philadelphia, Philadelphia, PA; Endocrinology Division, Pittsburgh Children’s Hospital, Pittsburgh, PA; Division of Pediatric Endocrinology, 12 A Committee of the Pediatric Endocrine Society was recently formed to develop guidelines for evaluation and management of hypoglycemia in neonates, infants, and children. To aid in formulating recommendations for neonates, in this review, we analyzed available data on the brief period of hypoglycemia, which commonly is observed in normal newborns during the transition from fetal to extrauterine life, hereafter referred to as transitional neonatal hypoglycemia in normal newborns. The goal was to better understand the mechanism underlying this phenomenon in order to formulate recommendations for recognizing neonates requiring diagnosis and treatment during the first days of life for disorders causing severe and persistent hypoglycemia. It has long been known that plasma glucose concentrations are lower in the first 1-3 days of life in normal newborn infants than at later ages. 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. 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. A National Institutes of Health conference outlined many of the “gaps in knowledge” about neonatal hypoglycemia and lamented the lack of a rational basis for defining hypoglycemia in neonates. For this re-evaluation of transitional neonatal hypoglycemia in normal newborns, we used the strategy routinely employed by pediatric endocrinologists for evaluation of hypoglycemia in older infants and children. This strategy, based on an examination of the major metabolic fuel and hormone responses to hypoglycemia, makes it possible to discover the mechanism of hypoglycemia and to make a specific diagnosis of the underlying cause (Figure; available at www.jpeds.com). We reviewed published data in normal newborns on metabolic fuel and hormone responses during the period of transitional neonatal hypoglycemia. We