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Abstract

Background

Early-childhood antibiotic exposure has been implicated in the development of chronic pediatric conditions, but many studies leave concerns about unmeasured confounding. We evaluated associations between early-childhood antibiotic exposure and allergic, autoimmune, or neurodevelopmental/psychiatric conditions.

Methods

We performed a retrospective cohort study using electronic health records data from the United Kingdom (1987-2020). The primary exposure was antibiotic prescriptions between birth and age 2 years. Outcomes were diagnoses of chronic pediatric conditions (asthma/allergic, autoimmune, and neurodevelopmental/psychiatric) or forearm fracture (negative control). Adjusted hazard ratios with 95% confidence intervals were estimated using multivariable Cox regression models adjusted for maternal, child, and area-based socioeconomic status. A sibling-matched analysis was conducted using conditional Cox regression.

Results

Among 1,091,449 children, antibiotic exposure before age 2 was positively associated with asthma (hazard ratio 1.24, 1.22-1.26), food allergy (hazard ratio 1.33, 1.26-1.40), and allergic rhinitis (hazard ratio 1.06, 1.03-1.10), with stronger associations observed following multiple antibiotic courses. Findings from sibling-matched analyses were similar. Early-childhood antibiotic exposure was also dose-dependently associated with intellectual disability (5+ vs. 1-2 courses: hazard ratio 1.73, 1.49-2.01; sibling-matched: 2.79, 1.87-4.18), but not with 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 bias.

Conclusions

Children receiving multiple antibiotic courses between birth and age 2 were more likely to develop asthma, food allergies, allergic rhinitis, and intellectual disability. However, risks of most autoimmune, neurodevelopmental, and psychiatric conditions studied were minimal following early-childhood antibiotic exposure.

antibiotics, pediatric, allergy, autoimmune, neurodevelopment, epidemiology, asthma, intellectual disability
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