Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exomesequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P < 4 × 10 −10 ), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P < 5 × 10 −10 ). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis.

Background Various environmental risk factors have been associated with the pathogenesis of inflammatory bowel disease. In this study we aimed to identify lifestyle factors that affect the onset of Crohn’s disease and ulcerative colitis. Methods 2294 patients from the Swiss IBD Cohort Study received a questionnaire regarding physical activity, nutritional habits and status of weight. In addition, a control group was formed comprising patients’ childhood friends, who grew up in a similar environment. Results Overall, 1111 questionnaires were returned (response rate: 48.4%). Significantly more patients with inflammatory bowel disease reported no regular practice of sport during childhood and beginning of adulthood compared to the control group (p = 0.0001). No association between intake of refined sugar and onset of inflammatory bowel disease was observed. More patients with Crohn’s disease compared to ulcerative colitis and controls suffered from overweight during childhood (12.8% vs. 7.7% and 9.7%, respectively; p = 0.027). Conclusions Our study underlines the relevance of environmental factors in the development of inflammatory bowel disease. Our results imply a protective effect of physical activity regarding the onset of inflammatory bowel disease.

Extremely preterm infants are prone to hyperglycemia which is associated with increased mortality and morbidity. Insulin sensitivity is variable in extreme prematurity, and its monitoring, prevention, and treatment are a significant challenge in the NICU. Frequent changes in fluid composition and volumes, as well as large growth and adaptational nutrient requirements are limited by difficult vascular access and blood sampling and risk of drug incompatibilities. Insulin treatment requires specific access and significantly increases fluid intake and sampling. Clinicians, therefore, often compromise by reducing glucose intake and accepting higher glycemia. We report a case series of 11 extremely low birth weight (ELBW) preterms, born between 23 5/7 and 27 6/7 weeks of gestation, treated for transient hyperglycemia during the first 2 weeks of life by continuous subcutaneous insulin infusion (CSII). Insulin concentration was 10 IU/ml, administered via 13 mm Accu-Chek® Tenderlink catheters and a commercial insulin pump (Accu-Chek® Combo, Roche Diabetes Care). Insulin treatment was initiated when glycemia was > 252 mg/dL (14 mmol/l) in two consecutive blood glucose determinations, except for one case when glycemia was 234 mg/dL (13 mmol/l), despite a previous decrease in glucose infusion rate. The starting dose for the CSII was between 0.01 and 0.08 IU/kg/h. The average duration of the CSII was 5 days (1–16 days). CSII in extreme preterm neonates with hyperglycemia was clinically feasible and practical by sparing IV lines and volume and appeared as more rapidly effective than continuous IV administration. No adverse events like hypoglycemia or skin infection were recorded.

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