(261) Exposure to antibiotics during pregnancy or early infancy and the risk of autoimmune disease in children: A nationwide cohort study with sibling matched analysis

Background: Pregnant women and infants often treat infection with antibiotics, but antibiotics itself can cause disruptions of the gut microbiota and alter immunity of the host. Accordingly, it could have a significant role on the onset of autoimmune disease. However, the risk of autoimmune disease among children associated with antibiotics use has not been fully addressed, challenged by indications or genetic factors.

Objectives: To investigate whether exposure to antibiotics during pregnancy or early infancy is associated with the risk of developing autoimmune diseases among children

Methods: We conducted a nationwide cohort study using mother-child linked claim database of Korea’s National Health Insurance Service. We included all pregnancies gave live birth for pregnancy analysis and all children for infant analysis between 2010 and 2019, who have records of infection. We defined exposure as at least 1 record of antibiotics prescription during pregnancy or early infancy which is first 6 months after birth. The outcomes of interest were type 1 diabetes mellitus, juvenile idiopathic arthritis, inflammatory bowel disease (ulcerative colitis, Crohn’s disease [CD]), autoimmune thyroiditis (Graves’ disease, Hashimoto’s). The antibiotics-exposed pregnancies were compared to unexposed in propensity score (PS)-matched analyses to adjust potential imbalances and confounding by indication. Further, sibling-matched analysis was performed to minimize bias from within-family confounders. Cox proportional hazard model was applied to assess the association between antibiotic use and the risk of autoimmune disease, and clinically relevant subgroup analyses for dose and number of classes of antibiotics were also conducted.

Results: We identified 882,850 PS-matched pairs of pregnancies for pregnancy analysis and 583,770 pairs of children for infant analysis. For pregnancy analysis, there was no association between antibiotics and all other autoimmune diseases, but CD showed an increased risk (HR 1.41, 95% CI 1.01 to 1.99), of which association attenuated in the sibling analysis. For infant analysis, exposure to antibiotics was also associated with a higher risk of CD and remained significantly increased HR (1.71, 1.06-2.77) even in sibling-matched analysis. Stronger positive association was found between CD and antibiotics during early infancy when cumulative dose and number of classes increase.

Conclusions: We found no association between exposure to antibiotics and the most of autoimmune diseases in children, while an elevated risk of CD associated with exposure during early infancy was observed. Given that the future investigation warrants to confirm the potential signal for CD, antibiotics use during early infancy needs to be used with more caution.