The identification of metabolic perturbations associated with the interaction of traffic-related air pollution exposure and dietary polyunsaturated fatty acids on birth weight z-score in the Atlanta African American Maternal-Child Cohort Restricted; Files Only

Abstract

Objective: This study investigated the interaction of prenatal exposure to several traffic-related air pollutants (TRAP) with the prenatal intake of individual and families of polyunsaturated fatty acids (PUFAs) on birth weight z-score (BWZS) and the maternal metabolome.

Materials and Methods: We estimated residential exposures to multiple TRAPs, including carbon monoxide (CO), fine particulate matter (PM2.5), and nitrogen oxides (NOx), during the first trimester and full pregnancy for each of the 297 participants enrolled in the Atlanta African American Maternal-Child Cohort whose pregnancy occurred between 2014-2018. Dietary intake of PUFAs was estimated by a food frequency questionnaire completed in early pregnancy. Multiplicative interaction was assessed using p-interaction and p-trend. Then, a metabolome-wide association study using untargeted serum metabolomics data from 236 participants was conducted to investigate how the interaction of NOx exposure during the full gestational period and docosahexaenoic acid (DHA) intake impacts the maternal metabolome. After false discovery rate (FDR) correction, we conducted pathway analysis and chemical annotation to identify perturbed pathways and metabolites with Level-1 evidence.

Results: Increased exposure to CO, PM2.5, and NOx during the first trimester and full pregnancy was associated with decreased BWZS. However, these relationships were weaker among those who consumed greater amounts of dietary PUFAs, including DHA (pintCO=0.09, pintNOx=0.06), compared to those who consumed lesser amounts. We extracted a total of 25,516 metabolic features that were associated with the interaction of DHA and NOx, of which 27 features were significant after FDR correction (q<0.2). There were 14 pathways enriched (p<0.05), many of which were related to lipid synthesis and utilization, and 30 metabolites were annotated with Level-1 evidence.

Conclusions: Increased TRAP exposure during the first trimester and full pregnancy was associated with decreased BWZS. However, these relationships were weaker among those who consumed greater amounts of dietary PUFAs. The interaction of DHA and NOx was associated with metabolic perturbations related to fatty acid biosynthesis and activation, suggesting alterations in the lipid profile. Due to the convenient translation of PUFAs to clinical intervention, these findings provide novel insights that precision dietary intervention can be used to attenuate the effect of TRAP exposure among susceptible populations.

Table of Contents

Chapter 1: Assessing the Interactive Effect of Traffic Related Traffic-Related Air Pollution (TRAP) and Dietary Polyunsaturated Fatty Acids (PUFA) on Birth Weight for Gestational Age in an African American Birth Cohort

Introduction………………………………………………………………………………………..2

Methods……………………………………………………………………………………………3

Results……………………………………………………………………………………………..7

Discussion…………………………………………………………………………………………8

Conclusions………………………………………………………………………………………11

References………………………………………………………………………………………..13

Tables & Figures…………………………………………………………………………………16

Appendices……………………………………………………………………………………….26

Chapter 2: Utilization of Untargeted High-Resolution Metabolomics to Identify Maternal Metabolites Associated with the Interaction of Nitrogen Oxides (NOx) Exposure and Dietary Docosahexaenoic Acid (DHA) Intake 

Introduction………………………………………………………………………………………28

Methods…………………………………………………………………………………………..29

Results……………………………………………………………………………………………35

Discussion………………………………………………………………………………………..36

Conclusions………………………………………………………………………………………39

References………………………………………………………………………………………..40

Tables & Figures…………………………………………………………………………………43

Appendices……………………………………………………………………………………….54

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	Health Sciences, Epidemiology Health Sciences, Public Health Environmental Health
Keyword	Pregnancy Metabolomics Nutrition Air Pollution
Committee Chair / Thesis Advisor	Donghai Liang, Emory University
Committee Members	Anne Dunlop, Emory University

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