Antibiotic Exposure and IBD Development Among Children: A Population-Based Cohort Study

Abstract

OBJECTIVE: To determine whether childhood antianaerobic antibiotic exposure is associated with the development of inflammatory bowel disease (IBD). METHODS: This retrospective cohort study employed data from 464 UK ambulatory practices participating in The Health Improvement Network. All children with ≥2 years of follow-up from 1994 to 2009 were followed between practice enrollment and IBD development, practice deregistration, 19 years of age, or death; those with previous IBD were excluded. All antibiotic prescriptions were captured. Antianaerobic antibiotic agents were defined as penicillin, amoxicillin, ampicillin, penicillin/β-lactamase inhibitor combinations, tetracyclines, clindamycin, metronidazole, cefoxitin, carbapenems, and oral vancomycin. RESULTS: A total of 1 072 426 subjects contributed 6.6 million person-years of follow-up; 748 developed IBD. IBD incidence rates among antianaerobic antibiotic unexposed and exposed subjects were 0.83 and 1.52/10 000 person-years, respectively, for an 84% relative risk increase. Exposure throughout childhood was associated with developing IBD, but this relationship decreased with increasing age at exposure. Exposure before 1 year of age had an adjusted hazard ratio of 5.51 (95% confidence interval [CI]: 1.66–18.28) but decreased to 2.62 (95% CI: 1.61–4.25) and 1.57 (95% CI: 1.35–1.84) by 5 and 15 years, respectively. Each antibiotic course increased the IBD hazard by 6% (4%–8%). A dose-response effect existed, with receipt of >2 antibiotic courses more highly associated with IBD development than receipt of 1 to 2 courses, with adjusted hazard ratios of 4.77 (95% CI: 2.13–10.68) versus 3.33 (95% CI: 1.69–6.58). CONCLUSIONS: Childhood antianaerobic antibiotic exposure is associated with IBD development.