Tae Yoon Lee ^1,2* John Petkau ³ Ariana Saatchi ² Fawziah Marra ² Stuart Turvey ^4,5 Hannah Lishman ⁶ David Michael Patrick ^7,8 Jacquelyn J Cragg ² Kate M Johnson ^1,2,9 Mohsen Sadatsafavi ^1,2

• ¹ Respiratory Evaluation Sciences Program, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada
• ² Collaboration for Outcomes Research and Evaluation, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada
• ³ Department of Statistics, Faculty of Science, University of British Columbia, Vancouver, British Columbia, Canada
• ⁴ Division of Allergy & Immunology, Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
• ⁵ British Columbia Children's Hospital, Vancouver, British Columbia, Canada
• ⁶ Community Antimicrobial Stewardship, BC Centre for Disease Control, Vancouver, British Columbia, Canada
• ⁷ British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
• ⁸ School of Population and Public Health, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
• ⁹ Division of Respiratory Medicine, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada

Background: Infant antibiotic use is associated with increased risk of asthma. We examined the population impact of antibiotic exposure in the first year of life on the burden of pediatric asthma in British Columbia, Canada, using simulation modeling. Methods: We performed a Bayesian meta-analysis of empirical studies to construct dose-response equations between antibiotic exposure in the first year of life and pediatric (<19 years of age) asthma. We used administrative health data to document trends in infant (< 1 year of age) antibiotic use in British Columbia during 2001 and 2018 (the study period). An independently developed microsimulation model of asthma was utilized to estimate asthma-related outcomes under three scenarios pertaining to the trends in antibiotic use during the study period: 1) observed trends, 2) flat trend in which the prescription rate remained at the 2001 value, and 3) intermediate trends midway between these two. We reported cumulative person-years with asthma, cumulative asthma incidence, and cumulative asthma exacerbations among the pediatric population during the study period. Results: There were 773,160 live births during the study period, with an average antibiotic prescription rate of 523 per 1,000 infants in the first year of life. The prescription rate decreased by 71.5% during the study period. In Scenario 1, there were 1,982,861 person-years with asthma, 183,392 asthma incident cases, and 383,072 exacerbations. Had the antibiotic exposure remained at the 2001 values (Scenario 2), there would have been additional 37,213 person-years with asthma, 10,053 asthma incident cases, and 23,280 exacerbations. Had the decline been half of the observed trend (Scenario 3), there would have been additional 20,318 person-years with asthma, 5,486 asthma incident cases, and 12,728 exacerbations. At least 80% of the excess burden in each outcome was attributable to the younger pediatric population of <10 years of age.The decline in infant antibiotic exposure has resulted in a substantial reduction in the burden of asthma in British Columbia. Such benefits should be considered when evaluating the value proposition of initiatives aimed at reducing unnecessary antibiotic exposure in early life.