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

项目摘要 怀孕期间暴露于交通相关空气污染（TRAP），城市空气污染的主要来源， 与不良的出生结果和儿童期特应性疾病的发展有关。值得注意的是， 有色人种和穷人社区，特别是非洲裔美国人（AA）妇女和儿童， 他们都经历了高TRAP暴露和不利的出生和儿童健康结果。的机制 母亲TRAP暴露如何影响出生结果和形成儿童健康差异的基础仍然是 大部分未知。这部分是由于在准确表征体内剂量方面的巨大挑战。 对TRAP的暴露和生物反应。高分辨率代谢组学（HRM）--高通量分析 方法涉及鉴定和定量与代谢相关的数千种代谢特征， 外源性暴露和内源性过程--已经成为改善暴露的有力工具 对复杂环境混合物的评价。在以前的成人和青少年工作中，我们使用HRM 检测暴露于城市空气污染后的代谢紊乱，我们发现并验证了 几种氧化应激和炎症相关途径与TRAP增加显著相关 暴露。这些有希望的初步发现和先前发表的关于TRAP介导的与出生相关的反应的工作 结果和儿童发育使我们假设怀孕期间接触TRAPs的增加 将导致特定代谢途径的干扰，特别是与氧化应激相关的代谢途径， 炎症，这将增加不良出生结果的风险，包括早产和小尺寸- 胎龄我们的多学科研究小组建议在320名队列中测试这一假设 具有良好表型出生结局和纵向高分辨率代谢谱的AA孕妇。在 这样做，我们将：1）使用 时空分辨源扩散模型（目标1）; 2）检查产前暴露于TRAP是否 与母体代谢组学中的扰动纵向相关（目的2）;以及3）探索母体是否 与TRAP暴露增加相关的代谢途径也与不良出生结局相关 (i.e.早产和小于胎龄儿）在调解框架下（探索性目标3）。的 拟议的交通暴露、母体代谢组和出生结局研究（TEMMBO研究）是高度 创新性地成为第一个纵向研究，以检查TRAP暴露，代谢紊乱 和不良出生结果在社会经济多样性，异常表型AA母婴队列。 这种联系将包括通过外部的新的暴露评估，交通排放暴露模型配对 内部的高分辨率代谢组学数据总之，结果将有助于确定 TRAP暴露与不良出生结局之间存在中度相关性， 采取干预措施，以改善受影响母亲和儿童的结果。

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.