{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T15:22:38Z","timestamp":1785338558527,"version":"3.55.0"},"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Health Fellowship Foundation","award":["Health Fellowship 2023"],"award-info":[{"award-number":["Health Fellowship 2023"]}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["No RS-2023-00208978"],"award-info":[{"award-number":["No RS-2023-00208978"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2024-00405650"],"award-info":[{"award-number":["RS-2024-00405650"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosmedicine.org"],"crossmark-restriction":false},"short-container-title":["PLoS Med"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods and findings<\/jats:title>\n<jats:p>A nationwide cohort study was conducted using mother-child linked claims database of Korea\u2019s 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\u2019s disease), systemic lupus erythematosus, and Hashimoto\u2019s 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], <jats:italic>p<\/jats:italic>-value\u2009=\u20090.132), juvenile idiopathic arthritis (HR 1.02, 95% CI [0.85, 1.22], <jats:italic>p<\/jats:italic>-value\u2009=\u20090.830), ulcerative colitis (HR 1.02, 95% CI [0.76, 1.37], <jats:italic>p<\/jats:italic>-value\u2009=\u20090.895), Crohn\u2019s disease (HR 1.16, 95% CI [0.98, 1.36], <jats:italic>p<\/jats:italic>-value\u2009=\u20090.076), systemic lupus erythematosus (HR 0.70, 95% CI [0.49, 1.01], <jats:italic>p<\/jats:italic>-value\u2009=\u20090.053), and Hashimoto\u2019s thyroiditis (HR 1.06, 95% CI [0.91, 1.23], <jats:italic>p<\/jats:italic>-value\u2009=\u20090.448). In the infancy analysis within the infection-restricted population, IPTW analyses showed no substantial differences in autoimmune disease risk between exposed and non-exposed groups for type 1 diabetes (IPTW HR 1.05, 95% CI [0.88, 1.26], <jats:italic>p<\/jats:italic>-value\u2009=\u20090.594) and juvenile idiopathic arthritis (HR 1.11, 95% CI [0.93, 1.33], <jats:italic>p<\/jats:italic>-value\u2009=\u20090.253), ulcerative colitis (HR 0.95, 95% CI [0.67, 1.36], <jats:italic>p<\/jats:italic>-value\u2009=\u20090.776), Crohn\u2019s disease (HR 1.07, 95% CI [0.91, 1.25], <jats:italic>p<\/jats:italic>-value\u2009=\u20090.403), systemic lupus erythematosus (HR 1.46, 95% CI [0.95, 2.26], <jats:italic>p<\/jats:italic>-value\u2009=\u20090.087), and Hashimoto\u2019s thyroiditis (HR 1.14, 95% CI [0.97, 1.33], <jats:italic>p<\/jats:italic>-value\u2009=\u20090.104). These results also showed similar associations in sibling-matched analyses. Subgroup analyses showed that maternal use of cephalosporins or antibiotics during first or second trimester was associated with a small increased risk of Crohn\u2019s disease in pregnancy analysis, while antibiotic exposure in males or during the first two months of life was associated with a modestly increased risk of autoimmune thyroiditis in infancy analysis. The primary limitations of this study include potential residual confounding due to unmeasured variables.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>In this nationwide cohort study, we found no association between early-life antibiotic exposure and the overall risk of autoimmune diseases in children. These findings underscore the importance of ensuring that antibiotic use during pregnancy and early infancy is guided by clear clinical indications and highlight the need for further research to explore subgroup-specific risks in greater detail.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pmed.1004677","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T17:30:57Z","timestamp":1755797457000},"page":"e1004677","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Exposure to antibiotics during pregnancy or early infancy and the risk of autoimmune disease in children: A nationwide cohort study in Korea"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4208-791X","authenticated-orcid":true,"given":"Eun-Young","family":"Choi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2622-6553","authenticated-orcid":true,"given":"Sungho","family":"Bea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyesung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahhyung","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Yeol","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Ha","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1010-7525","authenticated-orcid":true,"given":"Ju-Young","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,8,21]]},"reference":[{"key":"pmed.1004677.ref001","doi-asserted-by":"crossref","first-page":"102266","DOI":"10.1016\/j.coi.2022.102266","article-title":"The increasing prevalence of autoimmunity and autoimmune diseases: an urgent call to action for improved understanding, diagnosis, treatment, and prevention","volume":"80","author":"FW Miller","year":"2023","journal-title":"Curr Opin Immunol"},{"issue":"12","key":"pmed.1004677.ref002","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1056\/NEJMra020100","article-title":"The effect of infections on susceptibility to autoimmune and allergic diseases","volume":"347","author":"J-F Bach","year":"2002","journal-title":"N Engl J Med"},{"key":"pmed.1004677.ref003","doi-asserted-by":"crossref","first-page":"102193","DOI":"10.1016\/j.eclinm.2023.102193","article-title":"Global, regional, and national incidence of six major immune-mediated inflammatory diseases: findings from the global burden of disease study 2019","volume":"64","author":"D Wu","year":"2023","journal-title":"eClinicalMedicine"},{"issue":"5","key":"pmed.1004677.ref004","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.jadohealth.2010.08.019","article-title":"Mapping a global agenda for adolescent health","volume":"47","author":"GC Patton","year":"2010","journal-title":"J Adolesc Health"},{"issue":"9783","key":"pmed.1004677.ref005","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1016\/S0140-6736(11)60512-6","article-title":"Global burden of disease in young people aged 10\u201324 years: a systematic analysis","volume":"377","author":"FM Gore","year":"2011","journal-title":"Lancet"},{"key":"pmed.1004677.ref006","unstructured":"WHO. 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