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: 10372213
• 负责人: Donghai Liang
• 金额: $ 19万
• 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 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10372213
• 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.

项目总结