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

交通暴露、母亲代谢组和出生结果研究（TEMMBO 研究）

基本信息

批准号：
10217752
负责人：
Donghai Liang
金额：
$ 22.95万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-16 至 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10217752
关键词：
Address Adolescent Adult Affect African American Age Air Pollution Algorithms Allergic rhinitis Asthma Atopic Dermatitis Biological Biological Factors Biological Markers Birth Chemicals Child Child Development Child Health Childhood Clinical Color Communities Complex Data Development Disease Dose Drug Kinetics Enrollment Experimental Models Exposure to First Pregnancy Trimester Food Hypersensitivity Future Gestational Age Goals Growth Health Individual Inflammation Inorganic Chemicals Intervention Knowledge Link Longitudinal Studies Low Birth Weight Infant Maps Maternal and Child Health Measurement Mediating Mediation Metabolic Metabolic Pathway Methods Minority Groups Modeling Molecular Mothers Newborn Infant Organic Chemicals Outcome Outcome Study Oxidative Stress Participant Pathway interactions Phenotype Pregnancy Pregnant Women Premature Birth Process Publishing Research Research Personnel Resolution Risk Sampling Shapes Source Stress Technology Testing Third Pregnancy Trimester Toxic Environmental Substances Toxic effect Uncertainty Woman Work adverse birth outcomes adverse pregnancy outcome base cohort epigenome experience feature extraction follow-up health disparity high throughput analysis improved improved outcome in utero individual variation innovation metabolome metabolomics microbiome multidisciplinary neurodevelopment novel prenatal prenatal exposure response socioeconomics spatiotemporal tool toxicant traffic-related air pollution

项目摘要

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.

项目概要怀孕期间接触交通相关空气污染（TRAP）是城市空气污染的主要来源与不良出生结局和儿童期特应性疾病的发展有关。尤其，有色人种和穷人社区，特别是非裔美国 (AA) 妇女和儿童，比例过高经历高 TRAP 暴露和不良的出生和儿童健康结果。机制孕产妇 TRAP 暴露如何影响出生结果和塑造儿童健康差异的根本原因仍然存在很大程度上不为人知。这部分是由于准确表征内部剂量的巨大挑战 TRAP 的暴露和生物反应。高分辨率代谢组学 (HRM)——高通量分析涉及识别和量化与相关的数千种代谢特征的方法外源性暴露和内源性过程——已成为改善暴露的强大工具对复杂环境混合物的评估。在之前针对成人和青少年的工作中，我们使用了人力资源管理检测暴露于城市空气污染后的代谢扰动，我们在其中进行了识别和验证一些氧化应激和炎症相关途径与 TRAP 增加显着相关曝光。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果和儿童发育使我们假设妊娠期间 TRAP 暴露增加将导致特定代谢途径的扰动，尤其是与氧化应激和相关的代谢途径炎症，这会增加不良分娩结果的风险，包括早产和小尺寸胎龄。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出生结果和纵向高分辨率代谢分析的 AA 孕妇。在为此，我们将：1）使用以下方法生成个人水平 TRAP 暴露的回顾性估计时空分辨源色散模型（目标 1）； 2) 检查产前是否暴露于 TRAP 与母体代谢组扰动纵向相关（目标 2）； 3）探讨母亲是否与 TRAP 暴露增加相关的代谢途径也与不良出生结果相关（即早产和小于胎龄儿）在调解框架下（探索性目标 3）。这拟议的交通暴露、孕产妇代谢组学和出生结果研究（TEMMBO 研究）受到高度评价其创新之处在于，它是第一个检验 TRAP 暴露与代谢扰动之间联系的纵向研究社会经济多样化、表型异常的 AA 母婴群体中的不良出生结果。这种联系将包括通过外部交通排放暴露模型配对进行新型暴露评估具有内部高分辨率代谢组学数据。总之，结果将有助于确定影响因素 TRAP 暴露与不良出生结果之间存在中等关联，为旨在改善暴露母亲和儿童的结果的干预措施。