318 - Disrupting Early Immunity? Antibiotic Exposure and Asthma Risk in Childhood: Analysis of a Large Database

Publication Number: 2307.318

Ronald Argueta, Howard University College of Medicine, Silver Spring, MD, United States; Gianna Haskin, Howard University College of Medicine, Washington, DC, United States; Samar Khalil, Howard University College of Medicine, Washington, DC, United States; Cristofer Barry, Howard University College of Medicine, Washington, DC, United States; Elizabeth Beyene, Howard University College of Medicine, Washington DC, DC, United States; Syed Fahad Gillani, Howard University College of Medicine, Washington DC, DC, United States; Miriam Michael, Howard University College of Medicine, Washington, DC, United States

Background: Antibiotic exposure in infancy may influence long-term respiratory health, including asthma, yet prior studies report only modest associations (RR ~1.2–2.0). Asthma is the most common chronic pediatric disease, imposing substantial health and economic burdens. Identifying modifiable early-life risk factors is critical. We leveraged a large, real-world dataset to evaluate whether systemic antibiotic use during the first year of life is associated with asthma diagnoses in childhood, while rigorously accounting for demographic and clinical confounders.

Objective: To evaluate whether systemic antibiotic use during the first year of life is associated with asthma diagnoses in childhood, accounting for demographic and clinical confounders.

Design/Methods: Using TriNetX (2000–2022), we identified children with medical encounters and excluded those with congenital lung/heart malformations, cystic fibrosis, or pre-existing asthma. Exposure was any systemic antibiotic (ATC J01) during the first year. Outcome was asthma diagnosis (ICD-10 J45) between ages 4–12. Propensity score matching (1:1) balanced demographics (age, sex, race) and key clinical confounders (bronchiolitis, prematurity, eczema). Risk ratios (RR), odds ratios (OR), and Cox proportional hazards models were estimated. Sensitivity analyses examined robustness across sex, race, and comorbidity subgroups.

Results: Among 7.7M children (2.2M exposed, 5.5M unexposed), 1.93M remained in each group after matching, with excellent balance (all standardized mean differences < 0.03). Asthma incidence was 3.8% in the antibiotic group versus 0.9% in controls (RR 4.06, 95% CI 4.00–4.13; OR 4.18, 95% CI 4.11–4.25). Time-to-event analysis showed a hazard ratio of 2.60 (95% CI 2.56–2.64), indicating significantly lower asthma-free survival in the antibiotic group. Children with asthma who had prior antibiotic exposure experienced more repeat diagnoses (mean 5.4 vs 3.4), suggesting more severe or persistent disease.

Conclusion(s): Systemic antibiotic use in the first year of life was associated with a fourfold higher risk of asthma between ages 4–12. While residual confounding cannot be fully excluded, it is unlikely to account for this magnitude. Findings highlight a strong link between infant antibiotic exposure and later asthma risk, potentially mediated by early-life microbiome alterations influencing immune development. Results underscore the importance of antibiotic stewardship in infancy and have direct implications for pediatric practice. Further research should examine timing, antibiotic class, and mechanisms.