<p><strong>OBJECTIVES: </strong>The objective of this study was to characterize gut microbiome profiles of infants with congenital hyperinsulinism (HI) who underwent near-total or partial pancreatectomy for hypoglycemia management, as compared with healthy controls.</p>

<p><strong>METHODS: </strong>A prospective observational cohort study was performed. Subjects were infants (0-6 months) with HI who underwent removal of pancreatic tissue for management of intractable hypoglycemia from February 2017 to February 2018 at the Children's Hospital of Philadelphia. Fecal samples were collected postoperatively, on full enteral nutrition. The gut microbiome of HI subjects was analyzed and compared with age-matched samples from healthy infants.</p>

<p><strong>RESULTS: </strong>Seven subjects with ≥50% pancreatectomy and 6 with &lt;50% pancreatectomy were included. α (within-sample) diversity was lowest among infants with ≥50% pancreatectomy (richness: false discovery rate, 0.003; Shannon index: false discovery rate, 0.01). β (between-sample) diversity (Bray-Curtis dissimilarity, P = 0.02; Jaccard distance, P = 0.001) differed across groups (≥ or &lt;50% pancreatectomy, controls). Bifidobacteria and Klebsiella species were least abundant among infants with ≥50% pancreatectomy but did not differ between infants with &lt;50% pancreatectomy and historical controls.</p>

<p><strong>CONCLUSIONS: </strong>Infants with HI who underwent ≥50% pancreatectomy differed from age-matched infants in gut microbiome profile, whereas those with &lt;50% pancreatectomy more closely resembled control profiles. The durability of this difference should be investigated.</p>

<p>Feeding problems are frequent in infants with congenital hyperinsulinism (HI) and may be exacerbated by continuous enteral nutrition (EN) used to maintain euglycemia. Our center's HI team uses dextrose solution given continuously via gastric tube (intrasgastric dextrose, IGD) for infants not fully responsive to conventional medical therapy or pancreatectomy. Here, we describe our practice as well as growth, feeding, and adverse events in infants with HI exposed to IGD.</p>

<p><strong>METHODS: </strong>This was a retrospective cohort of infants with HI treated with IGD from 2009-2017. Primary outcomes were weight-for-length and body mass index Z-scores (WFL-Z and BMI-Z) in the year following IGD initiation. Secondary outcomes included EN use and adverse events. We used multivariable regression to assess covariates of interest.</p>

<p><strong>RESULTS: </strong>We studied 32 subjects (13 female) with a median age at IGD initiation of 73 days (range 17-367); median follow-up was 11.2 months (range 5.0-14.2). WFL-Z did not change significantly over time (p &gt; 0.05). EN use decreased significantly over time, i.e., at 0 months: 72% (95% CI 53-85) vs. at 12 months 39% (95% CI 22-59). No potential adverse events led to discontinuation of IGD.</p>

<p><strong>CONCLUSIONS: </strong>Over a median follow-up of nearly 1 year, IGD was well-tolerated, with no change in WFL-Z or BMI-Z from baseline.</p>

<p><strong>Context: </strong>Diazoxide, the only U.S. Food and Drug Administration-approved drug to treat hyperinsulinemic hypoglycemia, has been associated with several adverse events, which has raised concerns about the safety of this drug. Existing reports are limited to small studies and case reports.</p>

<p><strong>Objective: </strong>To determine prevalence of and clinical factors associated with adverse events in infants and children treated with diazoxide.</p>

<p><strong>Design: </strong>Retrospective cohort study of children with hyperinsulinism (HI) treated with diazoxide between 2003 and 2014.</p>

<p><strong>Setting: </strong>The Congenital Hyperinsulinism Center at the Children's Hospital of Philadelphia.</p>

<p><strong>Patients: </strong>Children and infants with laboratory-confirmed diagnosis of HI.</p>

<p><strong>Main Outcome Measures: </strong>Prevalence of pulmonary hypertension (PH), edema, neutropenia, thrombocytopenia, and hyperuricemia was determined. Tests of association and logistic regression were used to identify potential risk factors.</p>

<p><strong>Results: </strong>A total of 295 patients (129 female) met inclusion criteria. The median age at diazoxide initiation was 29 days (interquartile range, 10 to 142 days; n = 226 available start dates); 2.4% of patients were diagnosed with PH after diazoxide initiation. Children with PH (P = 0.003) or edema (P = 0.002) were born at earlier gestational age and more frequently had potential PH risk factors, including respiratory failure and structural heart disease (P &lt; 0.0001 and P = 0.005). Other adverse events included neutropenia (15.6%), thrombocytopenia (4.7%), and hyperuricemia (5.0%).</p>

<p><strong>Conclusion: </strong>In this large cohort, PH occurred in infants with underlying risk factors, but no identifiable risk profile emerged for other adverse events. The relatively high prevalence of neutropenia, thrombocytopenia, and hyperuricemia suggests the value in proactively screening for these side effects in children treated with diazoxide.</p>