Antibiotic timing, spectrum, and cumulative dose during pregnancy and infancy on risk of asthma

项目摘要 意义：妊娠期间给予抗生素，已被证明会改变微生物组 多样性，并进一步与儿童哮喘的风险增加有关。然而，目前尚不清楚， 时间、抗生素的范围和累积暴露在哮喘的发展中具有不同的作用。 具体目的：我们假设，在治疗期间，某些抗生素组的累积暴露量增加， 可确定的妊娠和婴儿期关键易感期增加了儿童哮喘的风险。到 确定某些抗生素的累积暴露会增加以下风险的关键时间段 儿童哮喘，我们将确定1）是否时间，频谱，和累积暴露的抗生素 在怀孕和婴儿期与儿童哮喘的风险增加; 2）是否 敏感时间段、抗生素谱和期间累积暴露量的组合 怀孕和婴儿期与儿童哮喘的风险增加有关。 研究设计：我们将使用田纳西州医疗补助计划进行一项基于人群的队列研究。 人群，已建立的PRIMA队列的一个子集（预防RSV：对发病率和哮喘的影响; R01 HS018454-01 PI Hartert）。在目标1中，我们将估计临界时间 周期，抗生素活性谱和累积暴露对儿童风险的影响 哮喘在目标2中，结合抗生素的时间、谱和累积暴露， 将对儿童哮喘进行分析。在所有目标中，将按孕产妇哮喘状态进行亚组分析 将抗生素效应与哮喘的遗传易感性区分开来。 影响：作为一种终身慢性疾病，目前还没有针对哮喘的一级预防策略。 抗生素被广泛用于治疗感染。我们的关键暴露期识别结果，安全 在怀孕和婴儿的每个发育阶段使用抗生素的最短时间，以及“较低风险” 抗生素具有重要的临床价值。研究结果将为临床医生、患者和政策制定者提供 决定抗生素使用的额外信息。

Project summary Significance: Antibiotic administration during pregnancy and has been demonstrated to alter microbiome diversity and further is associated with an increased risk of childhood asthma. It is unknown, however, whether timing, spectrum of antibiotics, and cumulative exposure have a differential role in the development of asthma. Specific Aims: We hypothesize that greater cumulative exposure of certain groups of antibiotics during definable critical susceptible period(s) of pregnancy and infancy increases the risk of childhood asthma. To identify the critical time period(s) when cumulative exposure of certain antibiotics increases the risk of childhood asthma, we will determine 1) whether timing, spectrum, and cumulative exposure of antibiotics during pregnancy and infancy are associated with an increased risk of childhood asthma; 2) whether combinations of the susceptible time period(s), spectrum of antibiotics, and cumulative exposure during pregnancy and infancy are associated with an increased risk of childhood asthma. Research Design: We will conduct a population based cohort study using the Tennessee Medicaid population, a subset of the established PRIMA cohort (Prevention of RSV: Impact on Morbidity and Asthma; R01 HS018454-01 PI Hartert) of 148,700 mother-child dyads. In aim 1, we will estimate the critical time periods, the spectrum of antibiotic activity, and the cumulative exposure individually on the risk of childhood asthma. In aim 2, the combination of timing, spectrum, and cumulative exposure of antibiotics on the risk of childhood asthma will be analyzed. In all aims, subgroup analyses by maternal asthma status will be conducted to differentiate the antibiotic effect from genetic predisposition to asthma. Impact: As a lifelong chronic disease, there is currently no primary prevention strategy available for asthma. Antibiotics are widely used to treat infection. Our results of identification of critical exposure period(s), safe minimum duration of antibiotics at each development stage of pregnancy and infancy, and “lower risk” antibiotics are of great clinical value. Findings of the study will provide clinicians, patients and policy makers additional information in decision making of antibiotic use.