Abstract

Abstract Background Early–life antibiotic exposure has been associated with a decreased richness of the microbiome, which is associated with the development of inflammatory bowel disease (IBD). The aim of this study was to assess the risk of developing paediatric-onset IBD (pIBD) after being exposed to systemic antibiotics during the first five years of life. Methods We identified all patients < 18 years old diagnosed with pIBD in Denmark between 1995-2018 in the National Patient Registry. Data on antibiotic prescriptions during first five years of life were retrieved from the National Prescription Register. PIBD patients were matched with up to ten healthy controls. Risk estimates were presented by Hazard ratios (HR). Results We identified 1,808 patients with pIBD (989 Crohn’s disease [CD]/819 ulcerative colitis [UC]) and 17,234 matched controls. An increased risk of developing pIBD was associated with prescription of antibiotics during first five years (HR = 1.32 [95%CI: 1.2-1.5], p= <0.0001), and risk was further increased if the patient had ≥ 4 antibiotic prescriptions compared to no antibiotic prescription (HR = 1.43 [95%CI: 1.2-1.6], p= <0.0001). Prescription of broad-spectrum antibiotics increased the risk of pIBD compared to prescription of only narrow-spectrum antibiotics (HR: 1.19, [95%CI 1.0-1.4], p=0.04). When stratified by IBD subtypes, only CD was significantly associated with exposure to antibiotics (HR = 1.43 [95%CI: 1.2-1.7], p=0.0003). Conclusion In this nationwide registry-based study, we found that antibiotic exposure during first five years of life, was associated with an increased risk of pIBD. Repeated antibiotic exposures increased risk estimates.

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