Air pollution, stress and urban child development

描述（由申请人提供）：越来越多的前瞻性流行病学研究将怀孕期间母亲的压力与儿童的不良神经发育联系起来。最近的证据还表明，围产期接触环境空气污染可能具有神经毒性作用。虽然历史上的研究主要集中在社会和物理环境因素如何独立影响儿童健康，但不断发展的研究强调了研究相互作用的重要性。此外，社会经济地位较低的边缘人群（SEP）生活在不利的社会环境或“社会”有毒的社区中，他们不成比例地暴露于与交通有关的污染物。因此，这些种群承受着越来越大的压力和越来越多的化学污染。在解释风险时，社会化学物质的相互作用可能比任何一个单独因素的主要影响更能解释差异。针对城市人口的相关研究很少，也没有研究将压力和空气污染混为一谈。关于围产期空气污染和/或压力与神经发育之间的机制途径的研究同样很少。我们利用一个已建立的妊娠队列——哮喘联盟社区、环境和社会压力（ACCESS）项目（R01 h080674, RJ Wright PI），对妊娠期开始的环境污染物暴露进行前瞻性特征分析，并对产前和产后压力以及相关混杂因素和介质进行广泛评估。我们可以从我们的生物标志物档案中提取，包括产前母体下丘脑-垂体-肾上腺（HPA）轴（例如皮质醇）的评估，6个月时婴儿自主神经系统（ANS）和HPA轴功能的评估，以及用于未来遗传分析的DNA库，以探索机制。在这个申请中，我们建议在n=815名6岁的ACCESS儿童中增加神经认知和行为测试。然后，我们将测试围产期暴露于慢性环境空气污染和/或心理压力对这些神经精神结果的主要影响。接下来，我们将研究空气污染的影响是否会被社会心理压力所改变。有待探索的机制包括围产期应激（和空气污染）引起的产妇产前HPA轴和儿童HPA轴和ANS反应的中断。最后，为了进一步探讨空气污染物和应激影响神经发育的生物学机制，我们将研究遗传易感性因素。

DESCRIPTION (provided by applicant): Increasingly, prospective epidemiological studies link maternal stress during pregnancy with adverse neurodevelopment in children. Recent evidence also suggests that perinatal ambient air pollution exposure may have neurotoxic effects. While historically research has focused on how social and physical environmental factors independently affect children's health, evolving research underscores the importance of studying interactive effects. Moreover, marginalized populations of lower-socioeconomic position (SEP) are exposed disproportionately to traffic- related pollutants while living in adverse social circumstances or communities that are "socially" toxic. Consequently, these populations experience both increased stress and increased chemical pollution. Social x chemical interactions may account for more variance in explaining risk than the main effects of either factor alone. Relevant studies in urban populations are rare and none assess stress and air pollution together. Studies of mechanistic pathways linking perinatal air pollution and/or stress to neurodevelopment are equally sparse. We take advantage of an established pregnancy cohort - the Asthma Coalition on Community, Environment, and Social Stress (ACCESS) project (R01 HL080674, RJ Wright PI), with prospectively characterized exposure to ambient pollutants starting in pregnancy coupled with extensive assessment of pre- and postnatal stress, as well as relevant confounders and mediators. We can draw from our biomarker archive including assessments of prenatal maternal hypothalamic-pituitary-adrenal (HPA) axis (e.g., cortisol), infant autonomic nervous system (ANS) and HPA axis function at age 6 months, and DNA banked for future genetic assays to explore mechanisms. In this application, we are proposing the addition of neurocognitive and behavioral testing in n=815 ACCESS children at age 6 years. We will then test the main effects of perinatal exposure to chronic ambient air pollution and/or psychological stress on these neuropsychiatric outcomes. We will next examine whether air pollution effects are modified by psychosocial stress. Mechanisms to be explored include perinatal stress (& air pollution)-elicited disruption in the maternal prenatal HPA axis and the child's HPA axis and ANS response. Finally, to further explore biological mechanisms by which air pollutants and stress impact neurodevelopment, genetic susceptibility factors will be examined. PUBLIC HEALTH RELEVANCE: This study will examine the effects of perinatal exposure to traffic-related air pollution on childhood neurobehavioral and cognitive development in urban children. In addition to independent effects of air pollution, the study will also examine the potential modifying effects of the social environment (i.e., psychological stress) and genetic susceptibility on these relationships. Such knowledge may inform efforts to design programs that improve neurodevelopmental trajectories in high-risk urban populations disproportionately exposed to adverse physical and social environments.