Abnormal Neurodevelopmental Outcomes are Common in Children with Transient Congenital Hyperinsulinism

Abstract

Introduction: Neuroglycopenia is recognized to be associated with abnormal neurodevelopmental outcomes in 26–44% of children with persistent congenital hyperinsulinism (P-CHI). The prevalence of abnormal neurodevelopment in transient CHI (T-CHI) is not known. We have aimed to investigate abnormal neurodevelopment and associated factors in T-CHI and P-CHI.Materials and Methods: A cohort of children with CHI (n = 67, age 2.5–5 years) was assessed at follow-up review and noted to have normal or abnormal (mild or severe) neurodevelopmental outcomes for the domains of speech and language, motor, and vision. Children were classified as P-CHI (n = 33), if they had undergone surgery or remained on medical therapy, or T-CHI (n = 34), if medical treatment for hypoglycemia was stopped.Results: Overall, abnormal neurodevelopment was present in 26 (39%) children with CHI, of whom 18 (69%) were severe. Importantly, the incidence of abnormal neurodevelopment in T-CHI was similar to that in P-CHI (30 vs. 47% respectively, p = 0.16). The prevalence of severe abnormal neurodevelopment in speech, motor, and vision domains was similar in both T-CHI and P-CHI children. For this cohort, we found that the severity of disease [based upon maximal diazoxide dose (odds ratio 95% confidence intervals) 1.3 (1.1; 1.5), p = 0.03], and early presentation of CHI <7 days following birth [5.9 (1.3; 27.8), p = 0.02] were significantly associated with abnormal neurodevelopment. There was no significant association with gender, genotype, or the histopathological basis of CHI.Conclusion: Abnormal neurodevelopment was evident in one third of children with both T-CHI and P-CHI, early presentation and severe CHI being risk factors. Early recognition and rapid correction of hypoglycemia are advocated to avoid abnormal neurodevelopment in children with CHI.

Rate of Serious Adverse Events Associated with Diazoxide Treatment of Patients with Hyperinsulinism

“…Since the early 1960s, researchers have shown that despite medical advances, the incidence of poor neurological outcome remains somewhere between 20 and 40% [1-4]. Transient forms of hyperinsulinism such as perinatal stress hyperinsulinism also occur and appear to carry similar risks of poor neurological outcome [3, 5]. …”

Hiperinsulinismo congénito del recién nacido: A propósito de un caso clínico

“…HC is an uncommon disorder of glucose metabolism, which is the most common cause of persistent hypoglycemia of the newborn [1][2][3] . Its pathogenesis lies in excessive production of insulin by pancreatic β cells, even with low blood glucose levels 8 .…”

“…Congenital hyperinsulinism (HC) is the main cause of persistent and recurrent hypoglycemia in the first year of life [1][2][3] . Its incidence ranges from 1/27,000 to 1/50,000 in newborns 4 .…”

“…Insulin secretion by pancreatic β cells is controlled to maintain fasting glucose normally between 63 and 99 mg/dl 7 . The importance of early diagnosis and treatment lies in neurological damage secondary to hypoglycemic states, which may be permanent [1][2][3]8 . Management requires metabolic stabilization with glucose supply and decrease insulin secretion, which is mainly achieved with diazoxide or somatostatin analogues (Octreotide) [9][10][11] .…”

A Brief Review of Hyperinsulinism in Small for Gestational Age Infants

“…A retrospective study in Manchester, UK showed that abnormal neurodevelopmental outcome is common in children with transient congenital Hyperinsulinism. (9) In their study, they followed a cohort of children with CHI between ages 2.5-5 years and assessed whether they have normal or abnormal neurodevelopmental outcomes in the domains of speech and language, Vision and motor. Children were classified as having persistent congenital hyperinsulinism of infancy (P-CHI), if they had undergone surgery or remained on medical therapy, or transient congenital hyperinsulinism of infancy (T-CHI) if medical treatment for hypoglycemia was stopped.…”