title: Abnormal Neurodevelopmental Outcomes are Common in Children with Transient Congenital Hyperinsulinism.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Paediatric Endocrinology, Royal Manchester Children's Hospital Manchester, UK.
authors.forename: Hima Bindu
authors.initials: HB
authors.lastname: Avatapalle
authors.forename: Indraneel
authors.initials: I
authors.lastname: Banerjee
authors.forename: Sajni
authors.initials: S
authors.lastname: Shah
authors.forename: Megan
authors.initials: M
authors.lastname: Pryce
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Nicholson
authors.forename: Lindsey
authors.initials: L
authors.lastname: Rigby
authors.forename: Louise
authors.initials: L
authors.lastname: Caine
authors.forename: Mohammed
authors.initials: M
authors.lastname: Didi
authors.forename: Mars
authors.initials: M
authors.lastname: Skae
authors.forename: Sarah
authors.initials: S
authors.lastname: Ehtisham
authors.forename: Leena
authors.initials: L
authors.lastname: Patel
authors.forename: Raja
authors.initials: R
authors.lastname: Padidela
authors.forename: Karen E
authors.initials: KE
authors.lastname: Cosgrove
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Dunne
authors.forename: Peter E
authors.initials: PE
authors.lastname: Clayton
keywords: congenital hyperinsulinism; developmental delay; hypoglycemia; neurodevelopment; neurological outcome; seizures; transient congenital hyperinsulinism