Physiological and phased approach to newborns at-risk of hyperinsulinemic hypoglycemia: A neonatal perspective

A neonatologist plays a critical role in the management of babies with hypoglycemia. Although neonatal hypoglycemia has been conventionally defined as glucose ≤2.5 mmol/L, levels ≤2.8 mmol/L among neonates raise concerns of neuroglycopenia, supporting the Pediatric Endocrine Societies' suggestion to target plasma glucose levels >2.8 mmol/L in at-risk infants 3.3 mmol/L for those aged >48 h. The neonatologist needs to identify at-risk babies and enroll them into a pathway that ensures safe, physiological transition to extrauterine life. Physiological transition constitutes early enteral feeding, navigating the glucose nadir while maintaining mother-child bonding. Smooth umbilical to enteral transition of glucose homeostasis following birth needs adequate glycogen stores and appropriate counter-regulatory hormone responses. When stores are inadequate and counter-regulatory responses fail, glucose regulation becomes more dependent on appropriate β-cell responses. However, β-cell dysregulation may cause inappropriate insulin secretion when hypoglycemic (hyperinsulinemic hypoglycemia [HH]) that can be transient, prolonged, or persistent. The majority comprise transient and prolonged forms of HH that recover in days to weeks with feeds or short-term parenteral glucose infusion or rarely with use of KATP channel agonist, diazoxide. The minority with persistent forms may have genetic mutations in at least 12 genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, UCP2, HNF4A, HNF1A, HK1, PGM1, and PGMM2) and need medical and/or surgical intervention, as well as long-term multidisciplinary specialist care. Although there is complexity to a management framework that begins in the first hours to days of life, a gentle, physiological, and phased approach can lead to better outcomes. This review article describes such an approach.