Aromatic compound metabolism and oxidative stress as potential mediators between ambient air pollution and hypertensive disorders of pregnancy--evidence from an MWAS study on Atlanta African American Maternal-Child Cohort Open Access

Abstract

Hypertensive disorders of pregnancies (HDP) are the most common medical disorder of pregnancy and a leading cause of maternal and infant morbidity and mortality. Previous studies have established an association between exposure to ambient air pollution and the occurrence of HDP, but the underlying biological mechanism is unclear, impeding targeted intention strategies. 

329 individuals from the Atlanta African American (AA) Maternal-Child cohort were included in the study (68 with HDP including 42 gestational hypertension and 26 preeclampsia). We employed liquid chromatography-high-resolution mass spectrometry to conduct metabolomics profiling on serum samples collected between 8-14 weeks of gestation and developed a spatiotemporally resolved model to estimate exposure to three common ambient air pollutants (PM2.5, NO2, and O3) during four critical exposure windows (1yr prior to conception, 1^st trimester, 1m and 1w prior to blood draw). We investigated overlapping features and pathways using a Meet-in-the-Middle Approach (MITM) and High-Dimensional Mediation Analysis (HDMA). 

13,980 and 11,106 metabolic features were extracted from HILIC and C18 chromatography columns. Several metabolites and pathways involved in oxidative stress and systemic inflammation are significantly associated with air pollutant exposures during critical exposure windows and HDP, including phenylalanine, indole, benzoate, LysoPC, degradation of the aromatic compound, and propionate metabolism. Biliverdin and porphyrin metabolism pathways are also associated with exposures and outcomes, indicative of potential hepatic impairment due to aromatic compound metabolism. 

Our findings suggest a potentially critical role of various aromatic compounds, indicative of oxidative stress, in the pathophysiology underlying the association between air pollution and HDP. 

Table of Contents

Tables of Contents

Introduction

Method

Results

Discussion

Conclusion

Reference

Tables and Figures

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, Public Health Health Sciences, Epidemiology Environmental Health
Keyword	Maternal and Child Health African American Oxidative Stress Air Pollution Hypertensive Disorders of Pregnancy Metabolomics
Committee Chair / Thesis Advisor	Donghai Liang, Emory University

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