Air Pollution and Autism in Denmark

 描述(申请人提供)：空气污染无处不在，但对它在胎儿时期可能对发育中的大脑产生的不利影响知之甚少。最近，有人假设空气污染作用于导致自闭症谱系障碍(ASD)的生物途径，ASD是儿童中最严重的神经发育障碍之一，在过去20年里，美国的发病率大幅上升。到目前为止，研究空气污染和自闭症的少数研究采用了各种粗略的暴露措施，或者规模较小，或者解释能力有限，因为它们只能对少数几项进行调整。 混杂因素。为了填补这一知识空白，我们将利用丹麦全国人口登记和复杂的个人水平空气污染暴露措施来评估胎儿发育关键期早期暴露于与交通相关的空气污染和颗粒物空气污染是否与ASD风险有关。丹麦拥有维护世界上最大的健康科学信息数据库之一的悠久传统，几十年来一直为所有居民提供税收支持的医疗保健和处方药保险；美国尚未提供数据。通过与丹麦的现有合作(R01ES013717、R03ES021643)，我们已经访问并对这些独特的资源有了扎实的了解。自1989年以来，约有8,087名丹麦儿童患有自闭症，我们的目标是将他们在出生年份和性别上与对照儿童按1：4的比例进行匹配。我们将利用一个复杂和有效的基于地理信息系统的扩散模型，AirGIS，来评估产前和早期暴露于与交通相关的空气污染和颗粒物污染。我们的合作者Raaschou-Nielsen博士成功地将交通污染物模型应用于癌症风险评估。6，7在AirGIS中，暴露量的建模基于作为交通污染混合物指示器的二氧化氮(NO2)/氮氧化物(NOx)，以及一个基于排放的全国模型，该模型在高空间和时间分辨率上提供PM2.5和PM10的估计；这两个模型都允许我们创建地址级别的单独暴露量。我们研究的具体目标是：(1)建立全球最大的基于人群的儿童自闭症和空气污染研究；(2)检验在胎儿发育的关键时期暴露于空气污染与自闭症相关的假设。此外，我们将使用丹麦国家出生队列(DNBC)，该队列招募了孕妇，并收集了约100,000名儿童(其中720名已被诊断为自闭症)在怀孕和早期生活期间广泛的前瞻性风险因素数据，以检查在怀孕期间评估的大量风险因素的潜在混淆偏向。我们将重点放在交通相关空气污染的个人水平估计上，这将促进对空气污染相关毒素及其对神经发育的有害影响的现有知识。此外，拟议的研究将为政策制定者提供证据，支持空气污染监管、运输和货物运输政策，并可能对保护易感儿童的神经功能产生影响。

 DESCRIPTION (provided by applicant): Air pollution is ubiquitous but very little is known about adverse effects it may have on the developing brain during fetal life. Recently it has been hypothesized that air pollution acts on biologic pathways contributing to autism spectrum disorder (ASD), one of the most severe neurodevelopmental disorders in children with large increases in incidence over the past two decades in the U.S.. The small number of studies to date that examined air pollution and autism have employed various crude exposure measures, or have been small in size, or have limited interpretability since they could only adjust for a few confounding factors. To fill this gap in knowledge we will utilize Danish nationwide population-based registers and sophisticated individual-level air pollution exposure measures to assess whether early life exposure to traffic-related and particulate air pollution during critical period of fetal development are associated with ASD risk. Denmark has a long-standing tradition of maintaining one of the world's largest health science information data banks and has provided tax- supported health care and prescription medication coverage for all residents for many decades; data not yet available in the U.S.. Through existing collaborations with Denmark (R01ES013717, R03ES021643), we have access to and gained a solid understanding of these unique resources. There are ~8,087 Danish children with ASD born since 1989 and we aim to match them on birth year and sex to a comparison population of control children at a ratio of 1:4 based. We will utilize a sophisticated and validated GIS-based dispersion model, AirGIS, to assess prenatal and early life exposures to traffic-related and particulate air pollution. Our collaborator, Dr. Raaschou-Nielsen, employed the traffic pollutant model successfully to assess cancer risk.6,7 Exposure is modeled in AirGIS based on nitrogen dioxides (NO2)/nitrogen oxides (NOx) serving as indicators for pollution mixtures from traffic and a nationwide emissions based model that provided estimates for PM2.5 and PM10 at high spatial and temporal resolution; both models allow us to create address level individual exposure measures. The specific aims of our study are to: (1) establish the largest nationwide population based study of childhood autism and air pollution worldwide; and (2) test the hypothesis that exposure to air pollution during critical periods of fetal development are associated with autism. In addition, we will use the Danish National Birth Cohort (DNBC) which enrolled pregnant women and collected extensive prospective risk factor data during pregnancy and early life for ~100,000 children among whom 720 are already diagnosed with ASD to examine potential confounding bias for a large number of risk factors assessed in pregnancy. Our focus on individual level estimates of traffic-related air pollution will advance existing knowledge about air pollution related toxins an their detrimental impact on neurodevelopment. Furthermore, the proposed study will provide policy makers with evidence to support air pollution regulation, transportation and goods movement policies and may have implications for the preservation of neurological function in susceptible children.