The Omics and Mixtures Integration on Traffic exposure and Preterm Birth (OMIT-PTB) Study - PROJECT SUMMARY Exposures to prenatal traffic-related air pollution (TRAP), a primary contributor to urban air pollution, have been linked to adverse birth outcomes including preterm birth (PTB). Notably, communities of color, especially African American people, are disproportionately exposed to high TRAP levels and experience elevated rates of PTB. The mechanisms underlying how maternal TRAP exposures may affect birth outcomes and shape child health disparities are still largely unknown, due, in part, to substantial challenges in accurately characterizing internal dose and biological responses to TRAP. Through the advancement in high-throughput analytical techniques and new bioinformatics methods, our work and the work of others have demonstrated that several omics platforms can be used in concert to identify sensitive biological signals associated with exogenous TRAP exposures and PTB. Existing studies, including our own, have been limited in refined exposure characterization, sample size (limiting ability to detect effects), focusing on a single exposure without much attention to mixture, and, most importantly, did not examine the specific mechanistic roles of each molecule from different omics layers and how they bridge the gap from TRAP exposures to PTB. To address these critical knowledge gaps, we propose the Omics and Mixtures Integration on Traffic exposure and Preterm Birth (OMIT-PTB) study to integrate and analyze longitudinal multi-omics data, spanning the maternal epigenome, metabolome, and microbiome, to characterize the molecular connections between maternal exposures to TRAP and PTB. Our innovative OMIT-PTB proposal will leverage the Atlanta African American Maternal-Child Cohort, an exceptionally phenotyped prospective pregnancy cohort. We will conduct state-of-art multi-omics profiling and integration during early and late pregnancy, innovative mixture analyses, and advanced assessment of cumulative and short-term exposures to TRAP on 700 pregnant people in this cohort. Specifically, we will conduct independent epigenome- (Aim 1), multi-stage metabolome- (Aim 2), and microbiome- (Aim 3) wide association studies to identify biological markers and pathways associated with prenatal TRAP exposures. Using advanced bioinformatic tools, we will conduct both a posteriori integration (Aim 4a) and a priori integration (Aim 4b) to simultaneously analyze multi-omics data to investigate the molecular connections between TRAP and PTB. The OMIT-PTB study will, for the first time, provide novel insights and comprehensive information on signatures of systemic biological perturbation linking TRAP exposures to PTB, leading to the identification of biological signals and markers (i.e., validated DNA methylation pattern at CpG sites, metabolites and metabolic pathways, microbial taxa and community types). These findings will contribute to elucidating potentially sensitive TRAP biomarkers and preclinical indicators for PTB - a meaningful step for defining novel intervention strategies to mitigate TRAP exposure risk and improve birth and health outcomes in exposed mothers and children.
