Impact analysis of infant antibiotic exposure on the burden of asthma: a simulation modeling study

Tae Yoon Lee, John Petkau, Ariana Saatchi, Fawziah Marra, Stuart Turvey, Hannah Lishman, David M. Patrick, Jacquelyn J Cragg, Kate M Johnson, Mohsen Sadatsafavi
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Abstract

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. Conclusions: 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.
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婴儿接触抗生素对哮喘负担的影响分析:模拟模型研究
背景:婴儿使用抗生素与哮喘风险增加有关。我们利用模拟模型研究了加拿大不列颠哥伦比亚省的人群在出生后第一年接触抗生素对小儿哮喘负担的影响。研究方法我们对实证研究进行了贝叶斯荟萃分析,构建了出生后第一年抗生素暴露与小儿(19 岁)哮喘之间的剂量-反应方程。我们利用行政健康数据记录了不列颠哥伦比亚省 2001 年至 2018 年(研究期间)婴儿(< 1 岁)抗生素使用的趋势。我们利用独立开发的哮喘微观模拟模型,对研究期间抗生素使用趋势的三种情况下的哮喘相关结果进行了估计:1)观察到的趋势;2)处方率保持在 2001 年值的持平趋势;3)介于这两种趋势之间的中间趋势。我们报告了研究期间儿科哮喘患者的累计人年、累计哮喘发病率和累计哮喘恶化率。研究结果研究期间共有 773 160 例活产,婴儿出生后第一年的平均抗生素处方率为 523/1000。在研究期间,处方率下降了 71.5%。在情景 1 中,共有 1,982,861 人年患有哮喘,183,392 例哮喘事件,383,072 例病情恶化。如果抗生素暴露量保持在 2001 年的水平(方案 2),哮喘患者将增加 37,213 人年、哮喘事件病例 10,053 例和病情加重 23,280 例。如果下降幅度是观察到的趋势的一半(情景 3),则哮喘患者将增加 20,318 人年、哮喘事件病例增加 5,486 例、病情恶化增加 12,728 例。每种结果中至少有 80% 的额外负担可归因于 10 岁以下的年轻儿科人群。结论:婴儿抗生素接触量的减少使不列颠哥伦比亚省的哮喘负担大大减轻。在评估旨在减少生命早期不必要的抗生素接触的措施的价值主张时,应考虑到这些益处。
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