Associations Between Early-Life Exposure to Different Antibiotic Agents and the Risks of Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder: A Nationwide Population-Based Study.

Background/

Objectives

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) substantially affect quality of life. Previous studies have not evaluated whether the associations between early-life antibiotic exposure and the risks of ASD and ADHD differ according to the antibiotic agents administered during infancy.

Methods

This nationwide case-control study used Taiwan's National Health Insurance Research Database, Birth Reporting Database, and Maternal and Child Health Database. The cohort included 1,693,718 term neonates born between 2004 and 2015 and followed through to 2022. For ASD (n = 7265) and ADHD (n = 39,056) cases, antibiotic-exposed children were matched 1:1 with unexposed children based on sex, gestational age, birth weight, and birth year. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazards models.

Results

Oral antibiotic exposure was associated with lower ASD but higher ADHD risk, while parenteral exposure was associated with increased risks of both outcomes. Amoxicillin and erythromycin exposure during the first year of life were associated with lower ASD risk, whereas ampicillin exposure at 4-12 months was associated with higher ASD risk (all p ≤ 0.033). For ADHD, exposure to amoxicillin/clavulanic acid, cefixime, ampicillin, and ampicillin/sulbactam was associated with increased risk, whereas erythromycin, cephalexin, and sulfamethoxazole-trimethoprim were associated with reduced risk (all p < 0.047).

Conclusions

Associations between early-life antibiotic exposure and the risks of ASD and ADHD varied according to antibiotic agents, route of administration, and timing of exposure. These findings may help explain inconsistencies among previous studies and inform antibiotic prescribing during infancy.