MON-087 Natural History and Neurodevelopmental Outcomes in Perinatal Stress Induced Hyperinsulinism

Abstract

BACKGROUND: Hyperinsulinism (HI) is the most common cause of persistent hypoglycemia in neonates, infants and children. Persistent hypoglycemia due to HI in the neonatal period and infancy has detrimental effects on the developing brain, leading to permanent brain damage. As such, neonatal hypoglycemia due to HI may be one of the most readily preventable causes of neurodevelopmental impairment. While monogenic forms of HI are rare with an estimated incidence in the US of 1:50,000 live births, perinatal stress-induced HI (PSIHI) is common and affects up to 50% of at-risk neonates, with an estimated incidence of 1:12,000 live births. There is a paucity of high quality evidence investigating neurodevelopmental outcomes in PSIHI. Methods: Subjects with HI and history of perinatal stress diagnosed between 2013 - 2018 and with demonstrated cure by fasting test by 2 years were included. Exclusion criteria included patients born prior to 32 wks gestation, congenital or syndromic HI and other diagnoses known to impact development. Medical records were reviewed and families were interviewed and asked to complete questionnaires for three validated neurodevelopmental assessments: ABAS-3, BRIEF-P, and CBCL (1.5–5). Results: Medical records of 98 eligible subjects were reviewed to date (74% males), 37% were born between 32–37 wks (mean gestational age 37.2 wks). Mean birth weight was 2.53kg. Median age of hypoglycemia presentation was 0 days, as 67% of subjects presented on day of life 0. Median age at HI diagnosis was 12 days, and the median length of time from first episode of hypoglycemia to definitive treatment was 14 days. Mean maximum glucose infusion rate was 12 mg/kg/min. 81% of subjects were successfully treated with diazoxide. Median time to demonstrated resolution of disease was 210 days. Parent interviews were completed for 33 subjects to date. Developmental concerns were reported by 52% of parents, and 41% reported pediatrician concerns. A diagnosis of speech delay was reported by 45% of parents, and 24% reported concerns for a learning disability. Behavioral concerns were reported by 45%, with 21% reporting diagnoses or specific concerns for ADHD and 12% reported diagnoses or strong concerns for autism. Neurodevelopmental assessments were completed in 15 subjects to date. The proportion of study subjects who scored more than 1 SD and 2 SDs outside the normal range on any of the major assessment scales was 33% and 6%, respectively (vs 15.8% and 2.2% in the general population for any individual scale). Conclusion: Children with PSIHI are predominantly male and most are born at term. While the majority of infants presented with hypoglycemia in the first day of life, diagnosis occurred most often 12 days later, with definitive treatment achieved after two weeks of life. Patients with PSIHI are at high risk of neurodevelopmental deficits, and are more likely to perform below average on developmental testing.