Neha Malhotra, Daphne Yau, Annaruby Cunjamalay, Buddhi Gunasekara, Athanasakopoulou S., Clare Gilbert, Kate Morgan, Mehul Dattani, Antonia Dastamani
Great Ormond Street Hospital for Children. University of Saskatchewan. Medical School of Queen Mary University.
United Kingdom and Canada
Clinical Endocrinology
Clin Endocrinol 2023;
DOI: 10.1111/cen.14987
Abstract
Objective: Transient hyperinsulinism (THI) is the most common form of recurrent hypoglycaemia in neonates beyond the first week of life. Although self-resolving, treatment can be required. Consensus guidelines recommend the lower end of the diazoxide 5-15 mg/kg/day range in THI to reduce the risk of adverse events. We sought to determine if doses <5 mg/kg/day of diazoxide can be effective in THI.
Design, patients, measurments: Infants with THI (duration <6 months) were treated with low-dose diazoxide from October 2015 to February 2021. Dosing was based on weight at diazoxide start: 2 mg/kg/day in infants 1000-2000 g (cohort 1), 3 mg/kg/day in those 2000-3500 g (cohort 2) and 5 mg/kg/day in those >3500 g.
Results: A total of 73 infants with THI (77% male, 33% preterm, 52% small-for-gestational age) were commenced on diazoxide at a median age of 11 days (range 3-43) for a median duration of 4 months (0.3-6.8), with no difference between cohorts. The mean effective diazoxide dose was 3 mg/kg/day (range 1.5-10); 35% (26/73) required an increase from their starting dose, including 60% (9/15) of cohort 1. There was no association between perinatal stress risk factors or treatment-related characteristics and dose increase. Adverse events occurred in 13 patients (18%); oedema (12%) and hyponatraemia (5%) were the most common. Two infants developed suspected necrotising enterocolitis (NEC); none had pulmonary hypertension.
Conclusion: Diazoxide doses <5 mg/kg/day are effective in THI. While the nature of the association between diazoxide and NEC was unclear, other adverse events were mild. We suggest considering starting doses as low as 2-3 mg/kg/day in THI to balance the side effect risk while maintaining euglycaemia.
Category
Class I. Drug-induced and Toxin-induced Pulmonary Hypertension
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Filed (PHiled). Greater than 1-2 years since publication
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