Management of Neonatal Hyperinsulinemic Hypoglycemia: Trends Over Nine Years

Abstract

Background: With increasing use of diazoxide for hyperinsulinemic hypoglycemia (HH), reporting of serious side effects of diazoxide such as pulmonary hypertension (PHT) increased.

Methods: Charts of all children diagnosed with HH during the study period and evaluated by Pediatric Endocrinology division of the Hasbro Children's Hospital were reviewed. We analyzed diazoxide use among infants with HH with focus on infants born small for gestational age (SGA) and preterm infants.

Results: Average timing of diazoxide initiation was later after 6/2017 compared to prior in preterm infants (45 days versus 4 days, p < 0.001) and in SGA infants (28 days versus 13 days, p < 0.001). Prescribing patterns changed further over time, corresponding with development of diazoxide-associated PHT in three infants between 10/2018-5/2020. Delays in diazoxide initiation were observed after 5/2020 compared to prior in full-term, non-SGA infants: 18 days versus12 days (p = 0.01). The proportion of SGA infants who received diazoxide was lower after 5/2020 compared to prior (23% versus 65%, p = 0.03). PHT developed in 12.5% of infants treated with diazoxide in this cohort, 75% of whom were preterm and/or SGA, and 75% were born to mothers with preeclampsia.

Conclusions: Patterns of diazoxide use changed over time, with delayed use in preterm and/or SGA infants observed after 6/2017, reduced use in SGA infants, and delayed initiation in all infants after 5/2020. PHT was not rare in our cohort, and was more likely in infants born SGA, preterm, or to a mother with preeclampsia.

Keywords: Congenital hyperinsulinism; diazoxide; hypoglycemia; neonatology; pulmonary hypertension.