Examining dietary modifiers of associations between air pollution and autism-related outcomes in two cohorts

项目总结 产前接触空气污染已多次被确定为自闭症谱系障碍(ASD)的危险因素， 支持与直径小于2.5微米的颗粒物(PM2.5)、臭氧和 二氧化氮(NO2)。来自其他领域的研究表明，饮食可能是空气污染风险的关键调节因素 与自闭症相关的途径，然而只有一项研究，考察了叶酸和空气污染的联合影响， 发表在ASD风险上。然而，叶酸以外的一系列饮食因素，包括多不饱和脂肪酸 多不饱和脂肪酸(PUFAs)和维生素D可能有助于抵消暴露的影响。此外，考虑到营养物质不会在 隔离，研究单一的营养物质与污染物的相互作用可能只提供了部分情况。此外，时间- 这种修改的窗口尚未确定。在拟议的研究中，我们将解决这些差距，并 在两个前瞻性研究中研究产前饮食如何改变空气污染物与自闭症相关结局的关系 一群人。护士健康研究3(NHS3)是一项持续的、来自全国各地的大型前瞻性护士队列 美国，包括怀孕的亚队列(n&gt；7000人)。自闭症早期风险纵向调查(EARLI) 是一个高危队列，跟踪已经生下患有自闭症孩子的母亲在随后的怀孕过程中 直到孩子3岁(n~200)。根据Social的说法，与ASD相关的结果将在这两项研究中获得 反应性量表(SRS)评分以及ASD诊断，使我们能够考虑这两个维度的特征 整个人群和诊断级别的风险。这两项研究都将有空气污染暴露的任务 来自相同方法的PM2.5、NO2和臭氧，以及来自经过验证的食物频率的产前营养数据 问卷调查。利用这些数据，我们的目标是：1)通过以下方式检查空气污染物-ASD关联的修改 叶酸、维生素D和多不饱和脂肪酸；2)评估与ASD相关的空气污染物和营养物质之间的相互作用 在多重暴露框架内的结果；以及3)检查空气污染-ASD关系的时间窗口 当饮食营养可能是最有效的时候。目标1分析将使用线性和逻辑回归来检查 在营养缺乏定义的层次内，分别与SRS评分和ASD诊断的相关性 在每个队列中的状态和以前的互动。在目标2中，我们将使用贝叶斯核机器回归(BKMR) 在更广泛的饮食背景下考虑营养与污染物的相互作用，考虑更广泛的营养素集 并考虑对ASD结局的潜在综合影响。在目标3中，我们将使用分布式滞后模型来 考虑空气污染物与ASD相关结果的潜在临界窗口，在这些窗口中 修改器可能具有最强的效果。在这项提案中，我们讨论了一个关键但未得到充分研究的研究领域。 由于空气污染暴露的广泛发生，以及因为饮食是一个容易获得、个人-- 由于水平是可改变的，该项目的研究结果可能会对公众健康产生重大影响。

PROJECT SUMMARY Prenatal air pollution exposure has been repeatedly identified as risk factor for autism spectrum disorder (ASD), with support for associations with particulate matter less than 2.5 microns in diameter (PM2.5), ozone, and nitrogen dioxide (NO2). Research from other fields suggests diet may be a key modulator of air pollution risks in pathways relevant to autism, yet only one study, examining the joint effects of folate and air pollution, has been published on ASD risk. However, a range of dietary factors beyond folate, including polyunsaturated fatty acids (PUFAs) and vitamin D, may serve to offset effects of exposures. In addition, given that nutrients do not act in isolation, studying single nutrient-pollutant interactions may provide only part of the picture. Further, time- windows for such modification have not been identified. In the proposed study, we will address these gaps and examine how prenatal diet may modify air pollutant associations with ASD-related outcomes in two prospective cohorts. The Nurses’ Health Study 3 (NHS3) is an ongoing, large prospective cohort of nurses from across the US that includes a pregnancy sub-cohort (n>7,000). The Early Autism Risk Longitudinal Investigation (EARLI) is a high-risk cohort that followed mothers who already had a child with ASD through a subsequent pregnancy until that child was age 3 (n~200). ASD-related outcomes will be captured in both studies according to Social Responsiveness Scale (SRS) scores, as well as ASD diagnosis, allowing us to consider both dimensional traits across the population and diagnostic-level risks. Both studies will have air pollution exposure assignments for PM2.5, NO2, and ozone from the same method and prenatal nutrient data from validated food frequency questionnaires. Using these data, our aims are to: 1) Examine modification of air pollutant-ASD associations by folate, vitamin D, and PUFAs; 2) Evaluate interactions between air pollutants and nutrients on ASD-related outcomes within a multi-exposure framework; and 3) Examine time windows in the air pollution-ASD relationship when dietary nutrients might be most impactful. Aim 1 analyses will use linear and logistic regression to examine associations with SRS scores and ASD diagnosis, respectively, within strata of nutrients defined by deficiency status and prior interaction in each cohort. In Aim 2, we will use Bayesian Kernel Machine Regression (BKMR) to consider nutrient-pollutant interactions within the context of broader diet, accounting for a wider set of nutrients and considering potential combined effects on ASD outcomes. In Aim 3, we will use distributed lag models to consider potential critical windows of air pollutant associations with ASD-related outcomes in which nutrient modifiers may have strongest effects. In this proposal we address a critical, yet understudied, area of research. Due to the widespread occurrence of air pollution exposure, and because diet is a readily accessible, individual- level modifiable factor, findings from this project present the potential for a large public health impact.