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的母亲压力与儿童的不利神经发育联系起来。最近的证据还表明，围产期环境空气污染暴露可能会产生神经毒性效应。虽然历史上的研究主要集中在社会和自然环境因素如何独立影响儿童的健康，但不断发展的研究强调了研究互动影响的重要性。此外，处于较低社会经济地位(SEP)的边缘化人口在生活在不利的社会环境或具有“社会”毒性的社区时，会不成比例地暴露在与交通有关的污染物中。因此，这些人口既经历了更大的压力，也经历了更多的化学污染。在解释风险时，社会x化学交互作用可能比任何一个因素单独的主要影响解释的差异更大。在城市人群中进行的相关研究很少，也没有人同时评估压力和空气污染。将围产期空气污染和/或压力与神经发育联系起来的机制路径的研究同样稀少。我们利用已建立的妊娠队列-哮喘社区、环境和社会压力联盟(ACCESS)项目(R01 HL080674，RJ Wright Pi)，前瞻性地描述了从怀孕开始暴露于环境污染物的特征，以及对产前和出生后应激的广泛评估，以及相关的混杂因素和调节因素。我们可以从我们的生物标记物档案中提取信息，包括产前评估孕妇下丘脑-垂体-肾上腺(HPA)轴(例如皮质醇)、婴儿自主神经系统(ANS)和6个月大时HPA轴的功能，以及为未来的遗传分析探索机制而储存的DNA。在这项应用中，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，我们将研究社会心理压力是否会改变空气污染的影响。有待探索的机制包括围产期应激(和空气污染)引起的母体产前HPA轴和儿童HPA轴以及ANS反应的中断。最后，为了进一步探索空气污染物和压力影响神经发育的生物学机制，将检查遗传易感因素。 公共卫生相关性：这项研究将研究围产期暴露于与交通相关的空气污染对城市儿童儿童神经行为和认知发展的影响。除了空气污染的独立影响外，这项研究还将研究社会环境(即心理压力)和遗传易感性对这些关系的潜在调整作用。这些知识可能有助于设计项目，改善暴露在不利物理和社会环境中的高危城市人口的神经发育轨迹。

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.