Early Short-course Diazoxide in Selected Neonates with Hyperinsulinemic Hypoglycemia: A Retrospective Observational Study
Meghana Srinath, Rabindran Chandran, Umamaheswari Balakrishnan, Prakash AmboiramBackground
Transient or perinatal stress-induced hyperinsulinemic hypoglycemia is common in neonates with fetal growth restriction (FGR), small-for-gestational-age (SGA) status, or other perinatal stressors. Diazoxide is an established therapy for hyperinsulinism, but the optimal timing, dose, monitoring strategy, and duration of treatment in presumed transient neonatal hyperinsulinism remain uncertain.
Objective
To describe glycemic outcomes and documented safety events among neonates with biochemically supported hyperinsulinemic hypoglycemia who received an institutional early short-course diazoxide strategy in inborn term and preterm neonates.
Methods
This retrospective observational study reviewed medical records from a tertiary neonatal intensive care unit (NICU) between 2019 and 2024. Neonates presenting with biochemically confirmed hyperinsulinemic hypoglycemia in the first 14 days of life (elevated insulin >2 µU/mL and negative capillary beta-hydroxybutyrate <0.8 mmol/L) were included regardless of diazoxide exposure.
Results
Thirty-six neonates were identified; 4 were excluded, leaving 32 neonates with hyperinsulinemic hypoglycemia. Diazoxide was administered to 28 neonates; 26 were classified as responders and two as non-responders. Among responders, FGR and small for gestational age were present in 20/26 (76.9%), and Doppler abnormalities in 17/26 (65.4%). Diazoxide was initiated at a median age of 5 days (range, 2-12) at 15 mg/kg/day with hydrochlorothiazide. The median documented interval to cessation of intravenous dextrose-containing fluids was 11 h (range, 5-28), and the median duration of diazoxide was 6 days (range, 4-10). No adverse events attributable to diazoxide were documented. However, standardized prospective monitoring for side effects was not performed.
Conclusion
In this single-center retrospective cohort, early short-course diazoxide use in selected neonates with presumed transient hyperinsulinemic hypoglycemia was associated with rapid documented discontinuation of intravenous dextrose among responders. These findings support feasibility and hypothesis generation, but well-powered studies with long-term follow-up are necessary to establish causality or routine suitability of early short-course diazoxide in selected neonates with hyperinsulinemic hypoglycemia.