Traffic Exposure, Maternal Metabolome and Birth Outcomes Study (TEMMBO Study)

项目总结 在怀孕期间暴露于与交通有关的空气污染(TRAP)，这是城市空气污染的主要来源， 与不良的出生结局和儿童时期的特应性疾病的发展有关。值得注意的是， 有色人种社区和穷人，特别是非裔美国人(AA)妇女和儿童，不成比例 经历高暴露的陷阱和不利的分娩和儿童健康后果。其作用机制 孕妇暴露于陷阱可能如何影响分娩结果和塑造儿童健康差距的潜在原因仍然是 很大程度上是未知的。这在一定程度上是由于在准确描述内照射剂量方面的巨大挑战。 对陷阱的暴露和生物学反应。高分辨代谢组学(HRM)--高通量分析 涉及识别和量化数千个与以下各项相关的代谢特征的方法 外源性暴露和内源性过程--已成为改善暴露的有力工具 对复杂环境混合物的评价。在之前对成年人和青少年的研究中，我们使用了人力资源管理 检测暴露于城市空气污染后的新陈代谢紊乱，我们在那里识别和验证 与TRAP增加显著相关的几个氧化应激和炎症相关途径 曝光。这些有希望的初步发现和之前发表的关于TRAP介导的与出生相关的反应的工作 结局和孩子的发育使我们假设，怀孕期间接触陷阱的机会增加 会导致特定代谢途径的紊乱，特别是那些与氧化应激和 炎症，这将增加不良分娩结局的风险，包括早产和小儿麻痹症 胎龄。我们的多学科研究团队建议在320人的队列中检验这一假设 具有良好表型分娩结局和纵向高分辨率代谢特征的AA孕妇。在……里面 这样做，我们将：1)生成个人水平陷阱暴露的回溯性估计，使用 时空分辨的源扩散模型(目标1)；2)检查产前暴露于陷阱是否 纵向上与母体代谢组的扰动有关(目标2)；以及3)探索母体 与TRAP暴露增加相关的代谢途径也与不良分娩结局有关 调解框架(探索性目标3)下的早产和小于胎龄儿)。这个 建议的交通暴露、母亲代谢和出生结局研究(TEMMBO研究)高度重视 具有创新性，是第一项研究陷阱暴露、代谢紊乱之间联系的纵向研究 以及在社会经济多样化、特殊表型的母婴队列中的不良生育结果。 这种联系将包括通过配对的外部交通排放暴露建模进行新的暴露评估 利用内部的高分辨率代谢组学数据。总而言之，结果将有助于确定 接触诱导剂和不良生育结局之间的适度关联，为 改善受感染母亲和儿童结局的干预措施。

PROJECT SUMMARY Exposures to traffic-related air pollution (TRAP), a primary source of urban air pollution, during pregnancy have been linked to adverse birth outcomes and the development of atopic diseases in childhood. Notably, communities of color and the poor, especially African American (AA) women and children, disproportionately experience both high TRAP exposures and adverse birth and child health outcomes. The mechanisms underlying how maternal TRAP exposures may affect birth outcomes and shape child health disparities are still largely unknown. This is due, in part, to the substantial challenges in accurately characterizing internal dose of exposures and biological responses to TRAP. High-resolution metabolomics (HRM) -- a high-throughput analysis method involving the identification and quantification of thousands of metabolic features associated with exogenous exposure and endogenous processes -- has emerged as a powerful tool to improve exposure assessment to complex environmental mixtures. In previous work among adults and adolescents, we used HRM to detect metabolic perturbations following exposures to urban air pollution, where we identified and verified several oxidative stress and inflammation-related pathways significantly associated with increased TRAP exposures. These promising initial findings and prior published work on TRAP-mediated response related to birth outcomes and child development have led us to hypothesize that elevated exposure to TRAPs during pregnancy will result in perturbations in specific metabolic pathways, especially those linked to oxidative stress and inflammation, which will increase risk for adverse birth outcomes including preterm birth and small-size-for- gestational age. Our multidisciplinary team of investigators proposes to test this hypothesis in a cohort of 320 AA pregnant women with well-phenotyped birth outcomes and longitudinal high-resolution metabolic profiling. In doing this, we will: 1) generate retrospective estimates of individual-level TRAP exposures using spatiotemporally-resolved source dispersion models (Aim 1); 2) examine whether prenatal exposure to TRAP is longitudinally associated with perturbations in maternal metabolome (Aim 2); and 3) explore whether maternal metabolic pathways that associate with increased TRAP exposures also associate with adverse birth outcomes (i.e. preterm birth and small-size-for-gestational age) under a mediation framework (Exploratory Aim 3). The proposed Traffic Exposure, Maternal Metabolome and Birth Outcomes Study (TEMMBO Study) is highly innovative in being the first longitudinal study to examine links among TRAP exposures, metabolic perturbations and adverse birth outcomes in a socio-economically diverse, exceptionally phenotyped AA maternal-child cohort. This linkage will include novel exposure assessment through external, traffic emission exposure modeling paired with internal, high-resolution metabolomics data. Together, results will contribute towards identifying factors that moderate associations between TRAP exposures and adverse birth outcomes, providing opportunities for interventions to improve outcomes in exposed mothers and children.