A national study on the effects of air pollution and temperature on children's neurodevelopmental outcomes

项目总结/摘要 有证据表明，某些发育障碍的患病率，特别是自闭症谱系， 自闭症（ASD）和注意缺陷多动障碍（ADHD）的发病率在近几十年急剧增加。 最近的研究表明，神经发育迟缓（NDD）具有中等遗传性，这表明 非遗传成分有助于其病因。环境介导的国家荒漠化和退化的估计年度费用 在美国儿童身上的花费是183亿美元。流行病学研究检查了产前和幼儿期暴露于空气的情况 污染物和NDDs，对不同污染物的影响，相互作用，敏感性， 暴露窗口和PM2.5的化学成分。此外，社会经济地位（SES）在 这些关联是复杂的。我们的首要目标是全面调查独立和联合 产前和幼儿期接触PM2.5、NO2和O3、PM2.5化学成分及其相互作用 温度对NDD的影响以及SES的改性效果。该应用程序的具体目标是：1）量化 产前和儿童早期暴露于PM2.5、NO2、O3、温度和NDD的关系，2）检查 产前和幼儿暴露于PM2.5化学形态和NDD之间的关联，以及3） 研究途径和协同效应，环境暴露和SES对NDDs之间。我们有 从两个基于人口的数据库-- Medicaid Analytic eXtract和IBM MarketScan-包括位置和个人层面的丰富信息 特色到8岁时，23.9%的公共保险儿童和11.0%的私人保险儿童 被诊断为1个或多个NDD。对于所有污染物，PM2.5化学成分和温度，我们 已经验证了对整个美国大陆的高分辨率每日预测。其中独特的成分 两个队列，使我们能够确定SES修改这些关联的程度。对于我们的分析，我们 将调整范围广泛的个人水平的特点和时空协变量。我们估计 使用考克斯回归，分布线性/非线性滞后模型， 我们将研究婴儿性别对效应的影响。我们将使用先进的统计方法来估计 混合物的影响。我们以前的工作和数据支持的假设和可行性的建议 study.这项研究是创新的，因为它将是第一项研究：1）调查协会 在全国范围内的空气污染物，温度和NDDs之间的关系; 2）使用最先进的时空模型 评估个人对PM2.5、NO2、O3和温度的暴露; 3）采用创新的临床数据资源 通过利用两个大的怀孕群体。该研究具有重要的指导意义 保护孕妇和儿童健康的决定和污染物法规， 预警系统，可能降低NDD的发病率以及随后的社会，财政和公共卫生负担。

PROJECT SUMMARY/ABSTRACT Evidence suggests that the prevalence of certain developmental disorders, specifically autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD), has increased sharply in recent decades. Recent studies have shown a moderate heritability for neurodevelopmental delays (NDDs), suggesting a nongenetic component contributing to its etiology. The estimated annual cost of environmentally mediated NDDs in US children is $18.3 billion. Epidemiologic studies examined prenatal and early childhood exposure to air pollutants and NDDs, with non-conclusive evidence on the effects of different pollutants, interactions, sensitive windows of exposure and chemical components of PM2.5. In addition, the role of socioeconomic status (SES) in these associations is complex. Our overarching goal is to comprehensively investigate the independent and joint prenatal and early childhood exposure to PM2.5, NO2 and O3, PM2.5 chemical components and interactions with temperature on NDDs as well as effect modification by SES. The specific aims of this application are: 1) Quantify the association prenatal and early childhood exposure to PM2.5, NO2, O3, temperature and NDDs, 2) Examine the association between prenatal and early childhood exposure to PM2.5 chemical speciation and NDDs, and 3) Examine pathways and synergistic effects, among environmental exposures and SES on NDDs. We have established a birth cohort of more than 4 million pregnancies from two population-based databases—the Medicaid Analytic eXtract and IBM MarketScan—that include rich information on location and individual-level characteristics. By 8 years of age, 23.9% of publicly insured children and 11.0% of privately insured children received a diagnosis of 1 or more NDDs. For all pollutants, PM2.5 chemical components and temperature, we have validated highly resolved daily predictions for the entire continental US. The unique composition of these two cohorts, allows us to determine the extent to which SES modifies these associations. For our analyses, we will adjust for a wide range of individual-level characteristics and spatiotemporal covariates. We will estimate hazard ratios and their 95% confidence intervals using cox regression, distributed-linear/non-linear lag models, and we will examine effect modification by infant sex. We will use advanced statistical methods to estimate the effects of mixtures. Our prior work and data support both the hypothesis for and the feasibility of the proposed study. The proposed research is innovative because it will be the first study to: 1) investigate associations between air pollutants, temperature and NDDs on a national scale; 2) use state-of-the-art spatiotemporal models to assess individual exposures to PM2.5, NO2, O3 and temperature; 3) employ innovative resources of clinical data by leveraging two large pregnancy cohorts. The proposed research is of great significance because it will guide decisions and pollutant regulations to protect the health of pregnant women and children, inform heat wave warning systems, potentially reducing rates of NDDs and subsequent social, financial, and public health burden.