Investigating the molecular mechanisms underlying the impact of prenatal exposures to traffic-related air pollution (TRAP) on newborn metabolome and adverse birth outcomes Restricted; Files Only

Abstract

Introduction: Air pollution is a significant environmental health risk that has been associated with adverse birth outcomes. However, the molecular mechanisms underlying this association remain unclear. This study aimed to investigate the impact of prenatal exposures to air pollutants on the newborn metabolome and adverse birth outcomes.

Methods: In this analysis, we included 48 participants from the Atlanta African American Maternal Child cohort. We estimated individual exposure to TRAP using air pollution high-resolution metabolomics assessment. We then performed high-resolution metabolomics analysis on newborn dried blood spots collected at delivery to assess the newborn metabolome. We used statistical analysis, metabolic pathway enrichment analysis, and metabolite annotation to identify pathways and metabolites that were associated with prenatal exposure to air pollutants. We also used meet-in-the-middle analysis to identify overlapping metabolites and pathways between prenatal exposure and adverse birth outcomes.

Results: We found that prenatal exposure to air pollution was associated with significant changes in the newborn metabolome. We identified several metabolic pathways that were significantly impacted by prenatal exposure to air pollutant, including biopterin metabolism, drug metabolism - cytochrome P450, lysine metabolism, tryptophan metabolism, and several vitamin metabolism pathways. Additionally, we identified two overlapping metabolites, DMABA NHS ester, and 3,4-dimethoxyphenylpropanoic acid, between maternal TRAP exposure and adverse birth outcomes.

Discussion: Our findings suggest that prenatal exposure to air pollutants may have significant impacts on the metabolome of newborns and contributes to adverse birth outcomes. The identification of specific metabolites and pathways may serve as potential biomarkers for future studies aimed at identifying high-risk populations and developing targeted interventions to mitigate the negative effects of air pollution on maternal and child health. However, this study also has some limitations, including a small sample size and lack of personal environmental monitoring data, which should be addressed in future studies.

Table of Contents

Table of Contents

Introduction. - 1 -

Method. - 2 -

Study population. - 2 -

Air pollution exposure assessment - 2 -

Measure of birth outcome. - 2 -

High-resolution metabolomics. - 2 -

Statistical analysis. - 3 -

Metabolic pathway enrichment analysis and metabolite annotation. - 4 -

Meet-in-the-middle analysis. - 5 -

Result - 5 -

Study population. - 5 -

MWAS model - 6 -

Pathway enrichment analysis. - 6 -

Metabolite annotation and confirmation. - 7 -

Discussion. - 7 -

Conclusion. - 10 -

Tables and Figures. - 11 -

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About this Master's Thesis

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School	Rollins School of Public Health
Department	Environmental Health
Degree	M.P.H.
Submission	Master's Thesis
Language	English
Research Field	Environmental Health
Keyword	Metabolome Newborn
Committee Chair / Thesis Advisor	Donghai Liang, Emory University

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