title: Feeding Problems Are Persistent in Children with Severe Congenital Hyperinsulinism.
abstract: BACKGROUND
  Congenital hyperinsulinism (CHI) is a rare but severe disorder of hypoglycemia in children, often complicated by brain injury. In CHI, the long-term prevention of hypoglycemia is dependent on reliable enteral intake of glucose. However, feeding problems (FPs) often impede oral glucose delivery, thereby complicating the management of hypoglycemia. FPs have not been systematically characterized in follow-up in a cohort with CHI.
  
  
  OBJECTIVE
  We aimed to determine the prevalence, types, and persistence of FPs in a cohort of children with CHI and investigate potential causal factors.
  
  
  METHODS
  FPs were defined as difficulty with sucking, swallowing, vomiting, and food refusal (or a combination) in an observational study in 83 children in a specialized CHI treatment center. The prevalence of FPs at diagnosis, 6, and 12 months after diagnosis were noted. Genetic mutation status and markers of severity of CHI were tested for association with FPs.
  
  
  RESULTS
  A third of children with CHI had FPs (n = 28), of whom 93% required antireflux medication and 75% required nasogastric and gastrostomy tube feeding. Sucking and swallowing problems were present at diagnosis but absent later. Vomiting was present in 54% at 6 months, while food refusal was present in 68% at 6 months and 52% at 12 months. The age at commencing and stopping nasogastric tube feeding did not correlate with FPs frequency at 6 and 12 months. Children with FPs had severe hypoglycemia at diagnosis and required glucagon infusion more often [odds ratio (OR) (95% confidence intervals) (95% CI) 28.13 (2.6-300.1), p = 0.006] to normalize glucose levels. FPs were more frequent in those with diffuse CHI undergoing subtotal pancreatectomy [n (%) = 10 (35%) vs. 0 (0%), p < 0.001], in contrast to those with spontaneous resolution [6 (22%) vs. 32 (58%), p = 0.002]. Those undergoing focal lesionectomy also had reduced FPs at 6 months after diagnosis [OR (95% CI) 0.01 (0.0-0.2), R (2) = 0.42, p = 0.004]. These observations suggest that persistence of hyperinsulinism was associated with FPs.
  
  
  CONCLUSIONS
  FPs occur in a significant proportion of children with CHI. Severe hyperinsulinism, rather than nasogastric tube feeding or medications, is the main factor associated with FPs.
authors.affiliation: Department of Paediatric Endocrinology, Royal Manchester Children's Hospital, Manchester, UK; Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.
authors.forename: Indraneel
authors.initials: I
authors.lastname: Banerjee
authors.affiliation: Department of Dietetics and Nutrition, Royal Manchester Children's Hospital , Manchester , UK.
authors.forename: Lynette
authors.initials: L
authors.lastname: Forsythe
authors.affiliation: Department of Paediatric Endocrinology, Royal Manchester Children's Hospital , Manchester , UK.
authors.forename: Mars
authors.initials: M
authors.lastname: Skae
authors.affiliation: Department of Paediatric Endocrinology, Royal Manchester Children's Hospital , Manchester , UK.
authors.forename: Hima Bindu
authors.initials: HB
authors.lastname: Avatapalle
authors.affiliation: Department of Paediatric Endocrinology, Royal Manchester Children's Hospital , Manchester , UK.
authors.forename: Lindsey
authors.initials: L
authors.lastname: Rigby
authors.affiliation: Department of Paediatric Endocrinology, Royal Manchester Children's Hospital , Manchester , UK.
authors.forename: Louise E
authors.initials: LE
authors.lastname: Bowden
authors.affiliation: Department of Paediatric Surgery, Royal Manchester Children's Hospital , Manchester , UK.
authors.forename: Ross
authors.initials: R
authors.lastname: Craigie
authors.affiliation: Department of Paediatric Endocrinology, Royal Manchester Children's Hospital , Manchester , UK.
authors.forename: Raja
authors.initials: R
authors.lastname: Padidela
authors.affiliation: Department of Paediatric Endocrinology, Royal Manchester Children's Hospital , Manchester , UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Ehtisham
authors.affiliation: Department of Paediatric Endocrinology, Royal Manchester Children's Hospital , Manchester , UK.
authors.forename: Leena
authors.initials: L
authors.lastname: Patel
authors.affiliation: Faculty of Life Sciences, University of Manchester , Manchester , UK.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Cosgrove
authors.affiliation: Faculty of Life Sciences, University of Manchester , Manchester , UK.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Dunne
authors.affiliation: Department of Paediatric Endocrinology, Royal Manchester Children's Hospital, Manchester, UK; Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Clayton
keywords: congenital hyperinsulinism; feeding; feeding problems; glucose; hypoglycemia; insulin