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.