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

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.