Early-Life Infections, Antibiotics and Later Risk of Childhood and Early Adult-Onset Inflammatory Bowel Disease: Pooled Analysis of Two Scandinavian Birth Cohorts

Abstract

Background: Childhood antibiotic use has been associated with inflammatory bowel disease (IBD), although the potential contribution of infection frequency remains uncertain. Aims: To explore the association between early-life infections, antibiotics and IBD development. Methods: We used population-based data from ABIS (Sweden) and MoBa (Norway) cohorts following children from birth (1997–2009) until 2021. Prospectively collected questionnaires identified infection frequency (any, gastrointestinal and respiratory) and antibiotics (any, penicillin and non-penicillin) until age 3. IBD diagnosis required ≥ 2 records in national health registries. Cohort-specific hazard ratios (aHR), adjusted for parental education, smoking and IBD were estimated and pooled using a random-effects model. Antibiotic analyses were adjusted for infection frequency. Results: There were 103,046 children (11,872 ABIS and 91,174 MoBa), contributing to 1,663,898 person-years of follow-up, during which 395 were diagnosed with IBD. The frequency of any infection at 0 to < 1 and 1 to < 3 years showed a pooled aHR of 1.01 (95% confidence interval [CI] = 0.96–1.07) and 1.00 (95% CI = 0.99–1.01) per additional infection for IBD. Adjusting for infections, any versus no antibiotics in the first year was associated with IBD (pooled aHR = 1.33 [95% CI = 1.01–1.76]). The aHR for additional antibiotic course was 1.17 (95% CI = 0.96–1.44), driven by penicillin (per additional course, aHR = 1.28 [95% CI = 1.02–1.60]). Although antibiotics at 1 to < 3 years did not show an association with IBD or Crohn's disease, non-penicillin antibiotics were associated with ulcerative colitis (per additional course, aHR = 1.95 [95% CI = 1.38–2.75]). Conclusion: Early-life antibiotic use was, a significant risk factor for childhood and early adult-onset IBD, independent of infection frequency.