Impact of preconception and onward exposure to air pollution on growth trajectories of infants and children (R01)

项目总结/摘要 儿童期肥胖是儿童期和成年期许多慢性疾病的危险因素。热量过多 消费、体育活动不足和遗传是肥胖症流行迅速发展的重要因素; 但新出现的证据表明，早期暴露于空气污染的作用， 配子成熟并持续到整个童年的时期。尽管世界上92%的人口 根据2016年世卫组织的一份报告，今天生活在环境空气质量超过健康限值的地方， 研究评估了潜在的关键时间窗口，包括孕前时期，在此期间，空气 污染暴露可能会对出生体重和生长轨迹产生不利影响，这是两个重要的预测因素， 儿童肥胖症 在这里，我们提出了一个总体假设，即空气污染暴露在关键的早期 孕前、子宫内和生命头2年的生命发育期与肥胖相关 发育障碍，表现为低出生体重和早期较高的生长轨迹 童年.我们建议在20,000名新生儿中检验这一假设，这些新生儿的父亲和母亲都有 2016-2018年，在29家医院入组上海孕前队列研究（SPCC）。 这些新生儿中的每一个都有详细的父亲和母亲孕前基线健康，膳食补充剂， 吸烟、饮酒和人口统计学数据，详细的孕产妇妊娠信息，以及出生 结果数据。在他们生命的前2年，这些新生儿有多达6个预定的身体和健康 考试，为我们提供数据来计算体重和身高，潜在的非线性，生长轨迹和评估 相关的产后变量，如母乳喂养，感染和疾病。在20，000个住宅中， 由于研究对象的不同，污染物的时空变异性异常大， 特别是与交通有关的空气污染物。我们将使用最先进的时空曝光技术 模型，用10个政府监测站的空气监测数据和我们的补充空气污染数据进行验证 测量，以计算一组指定时间窗内居住地址的污染物浓度 包括母亲和父亲（分别）的敏感孕前期、妊娠月数和 妊娠期和婴儿期的前两年。通过利用这一大型纵向数据库的丰富数据集， 两万名儿童组成的队列， 我们将使用分布式滞后模型来确定关键的暴露窗口，并检查 儿童性别、社会经济状况和父母吸烟状况等因素的潜在影响差异 从怀孕前到怀孕期。如果我们的假设被证明是正确的，这项研究将提供第一个科学的 在关键时间窗内，支持父亲和母亲空气污染暴露的证据，包括 怀孕前和子宫内时期，作为低出生体重和儿童期身体过度生长的风险因素。

PROJECT SUMMARY/ABSTRACT Childhood obesity is a risk factor for many chronic diseases in childhood and adulthood. Excessive calorie consumption, inadequate physical activity, and genetics are important factors in the burgeoning obesity epidemic; but emerging evidence suggests a role for early-life exposure to air pollution, beginning at the preconception period of gametes maturation and continuing into the entire childhood. Despite that 92% of world’s population today lives in places where ambient air quality exceeds health-based limits per a 2016 WHO report, no published studies have assessed the potential critical time windows, including the preconception period, during which air pollution exposures may adversely affect birth weight and growth trajectory, two significant predictors for childhood obesity. Here we present an overarching hypothesis that air pollution exposures during critical early life developmental periods of preconception, in utero, and first 2 years of life, are associated with obesity-related developmental perturbations, which is manifested by low birth weight and higher growth trajectories during early childhood. We propose to examine this hypothesis in 20,000 newborns whose fathers and mothers have both been enrolled in the Shanghai PreConception Cohort (SPCC) throughout 29 hospitals from year 2016-2018. Each of these newborns has detailed paternal and maternal preconception baseline health, dietary supplement, smoking, alcohol consumption, and demographic data, detailed maternal gestational information, and birth outcome data. During their first 2 years of life, these newborns have up to 6 scheduled physical and health exams, providing data for us to calculate weight and height, potentially non-linear, growth trajectories and assess relevant postnatal variables such as breast-feeding, infection, and illness. Across the 20,000 residence addresses of study subjects, there exist unusually large temporal and spatial variabilities in pollutant concentrations especially for traffic related air pollutants. We will use cutting-edge tempo-spatial exposure models, validated with air monitoring data from 10 governmental stations and our supplementary air pollution measurements, to compute pollutant concentrations at residence addresses for a set of specified time windows including sensitive preconception periods for mothers and fathers (respectively), gestational months and trimesters, and throughout the first 2 years of infancy. By leveraging the rich dataset of this large longitudinal cohort of 20,000 children, we will use distributed lag models to identify critical exposure windows and to examine potential effect differences by factors such as child sex, social economic status and parental smoking status from preconception to gestation periods. If our hypothesis is proven true, this study will provide the first scientific evidence supporting paternal and maternal air pollution exposure during critical time windows, including preconception and in utero periods, as a risk factor for low birth weight and excessive body growth in childhood.