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）

• 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
• 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

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.

项目摘要 与交通相关的空气污染暴露（TRAP）是城市空气污染的主要来源，怀孕期间 与不良的出生结局和儿童特应性疾病的发展有关。尤其， 有色人种和穷人，尤其是非裔美国人（AA）妇女和儿童的社区，不成比例地 体验高陷阱暴露和不良的出生和儿童健康成果。机制 孕产妇陷阱暴露可能会影响出生结果和形状的儿童健康差异的基础 在很大程度上未知。这部分归因于准确表征内部剂量的重大挑战 暴露和生物学对陷阱的反应。高分辨率代谢组学（HRM） - 高通量分析 涉及识别和量化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 评估复杂的环境混合物。在成年人和青少年的先前工作中，我们使用了HRM 在暴露于城市空气污染后发现新陈代谢的扰动，我们在其中确定和验证 几种氧化应激和炎症相关途径与陷阱增加显着相关 暴露。这些有希望的初始发现和事先发表的有关与出生有关的陷阱介导的反应的工作 结果和儿童发展使我们假设怀孕期间陷阱的暴露率升高 将导致特定代谢途径的扰动，尤其是与氧化应激相关的途径 炎症，这将增加出现不良出生结果的风险，包括早产和小型大小。 胎龄。我们的多学科研究人员建议在320的队列中检验这一假设 AA孕妇具有良好的分型出生结果和纵向高分辨率代谢分析。在 这样做，我们将：1）使用使用个人级陷阱暴露的回顾性估计 时空分辨源分散模型（AIM 1）； 2）检查产前暴露于陷阱 纵向与母体代谢组的扰动相关（AIM 2）； 3）探索是否有母亲 与陷阱暴露增加的代谢途径也与不良的出生结果相关 （即早产出生和小型胎龄）在调解框架下（探索目的3）。这 拟议的交通暴露，母体代谢组和出生结果研究（TEMMBO研究）高度高 创新是首次研究陷阱暴露之间联系的纵向研究，代谢扰动 在社会经济多样化的，异常表现为AA母子的同龄人中。 这种联系将包括通过外部的交通排放曝光建模配对的新型暴露评估 具有内部高分辨率代谢组学数据。结果共同将有助于确定因素 陷阱暴露与不良出生结果之间的适度关联，为 干预措施以改善裸露的母亲和儿童的预后。