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. 2025 Sep 15;232(3):659-668.
doi: 10.1093/infdis/jiaf191.

Early Childhood Antibiotics and Chronic Pediatric Conditions: A Retrospective Cohort Study

Matthew A Beier  1   2 , Soko Setoguchi  3   4   5 , Tobias Gerhard  4   5   6 , Jason Roy  4   5 , Dawn Koffman  4 , Dinesh Mendhe  7 , Joanna Madej  1   8 , Brian L Strom  4   9 , Martin J Blaser  3   10 , Daniel B Horton  4   5   11
Affiliations

Early Childhood Antibiotics and Chronic Pediatric Conditions: A Retrospective Cohort Study

Matthew A Beier et al. J Infect Dis. .

Abstract

Background: Early childhood antibiotics have been implicated in chronic pediatric conditions, but many studies leave concerns about unmeasured confounding. We evaluated associations between early childhood antibiotics and multiple pediatric conditions.

Methods: We performed a retrospective cohort study using electronic health records data (United Kingdom, 1987-2020). The primary exposure was antibiotic prescriptions between birth and age 2 years. Outcomes were newly diagnosed chronic pediatric conditions (asthma/allergic, autoimmune, neurodevelopmental/psychiatric) or forearm fracture (negative control). Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using multivariable Cox regression models adjusted for maternal, child, and area-based socioeconomic covariates. Sibling-matched analyses were conducted using conditional Cox regression.

Results: Among 1 091 449 children, antibiotic exposure before age 2 was positively associated with asthma (HR, 1.24 [95% CI, 1.22-1.26]), food allergy (HR, 1.33 [95% CI, 1.26-1.40]), and allergic rhinitis (HR, 1.06 [95% CI, 1.03-1.10]), with stronger associations with multiple antibiotic courses. Sibling-matched analyses yielded similar findings. Early childhood antibiotic exposure was also dose-dependently associated with intellectual disability (≥5 vs 1-2 courses: HR, 1.73 [95% CI, 1.49-2.01]; sibling-matched: HR, 2.79 [95% CI, 1.87-4.18]). Consistent associations were not observed for celiac disease, inflammatory bowel disease, juvenile idiopathic arthritis, psoriasis, type 1 diabetes, attention-deficit/hyperactivity disorder, autism spectrum disorders, or anxiety. Sibling-matched results and a negative control outcome suggested minimal confounding.

Conclusions: Children receiving multiple antibiotic courses before age 2 were more likely to develop asthma, food allergies, allergic rhinitis, and intellectual disability. However, antibiotic-associated risks of most autoimmune, neurodevelopmental, and psychiatric conditions studied were minimal.

Keywords: allergy; antibiotics; asthma; intellectual disability; pediatric.

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Conflict of interest statement

Potential conflicts of interest. S. S. has received research funding from BMS, Daiichi Sankyo, and Pfizer Japan (provided to Rutgers University, unrelated to this work); has received consulting fees from Merck Inc and Pfizer Japan; and has served on the BMS Hypertrophic Cardiomyopathy Registry advisory board and the independent data review committee for Regeneron Pharmaceuticals. B. L. S. has received consulting fees from Janssen Pharmaceuticals, Lundbeck, Johnson & Johnson, Pharmacosmos, AbbVie, and the Consumer Healthcare Products Association. M. J. B. has received research funding from the Emch Foundation, Sergei Zlinkoff Foundation, C & D Fund, and Danisco USA Inc (provided to Rutgers University, unrelated to this work) and has received consulting fees from Procter and Gamble, Moderna, Elysium Health, Seed Health, and FARE (Food Allergy Research & Education, Inc). D. B. H. has received research funding from Danisco USA Inc and the Arthritis Foundation (provided to Rutgers University, unrelated to this work); research funding and salary support from the Childhood Arthritis and Rheumatology Research Alliance (provided to Rutgers University, unrelated to this work); and honoraria from the American College of Rheumatology (unrelated to this work). All other authors report no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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