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 1072426 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 1.52/10000 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.

FIGURE 1

Latency period between first diagnosis for IBD-related symptoms (eg, abdominal pain) and first IBD diagnosis. Each bar represents a 1-month interval.

FIGURE 2

A, Proportion of subjects developing IBD according to age and antianaerobic antibiotic exposure status. P < .001 for the difference between groups by using the log-rank test. B, proportion of subjects developing IBD according to age and antianaerobic antibiotic exposure level. P < .001 for the difference among groups by using the log-rank test.

FIGURE 3

Hazard of developing IBD if ever previously exposed to antianaerobic antibiotics, according to age.