Classification of antibiotics.

Background Emerging evidence suggests that prenatal or early-life exposure to antibiotics may contribute to the development of autoimmune diseases in children. However, previous studies investigating this association have yielded conflicting and inconclusive results, partly due to challenges related to confounding by indication and underlying genetic or familial factors. Methods and findings A nationwide cohort study was conducted using mother-child linked claims database of Korea’s National Health Insurance Service between 2008 and 2021. Among individuals with diagnosis of infections, children exposed to antibiotics during pregnancy or early infancy were compared to those who were not exposed. The autoimmune-related outcomes of interest were the onset of type 1 diabetes, juvenile idiopathic arthritis, inflammatory bowel disease (ulcerative colitis, Crohn’s disease), systemic lupus erythematosus, and Hashimoto’s thyroiditis. The antibiotic-exposed pregnancies were compared to unexposed pregnancies using inverse probability of treatment weighting (IPTW) methods to adjust for potential imbalances and confounding by indication. Also, sibling-matched analyses were performed to minimize bias from within-family confounders. Cox proportional hazard model was applied to assess associations, and clinically relevant subgroup analyses, including sex, subclasses and exposed timing of antibiotics were also conducted. Before IPTW, we identified 1,516,574 exposed children and 1,186,516 unexposed children for pregnancy analysis, and 1,925,585 exposed and 1,421,464 unexposed for the infancy analysis. In the pregnancy analysis within the infection-restricted population, IPTW analyses showed null association between antibiotic exposure and autoimmune diseases, including type 1 diabetes (IPTW HR 1.14, 95% CI [0.96, 1.35], p -value = 0.132), juvenile idiopathic arthritis (HR 1.02, 95% CI [0.85, 1.22], p -value = 0.830), ulcerative colitis (HR 1.02, 95% CI [0.76, 1.37], p -value = 0.895), Crohn’s disease (HR 1.16, 95% CI [0.98, ...