Biological Mechanisms for Per and Poly-fluoroalkyl Substances (PFAS) Exposure Effects on Fetal Growth among Pregnant African American Women in Atlanta, Georgia Open Access

Chang, Che-Jung (Summer 2021)

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Exposure to per and poly-fluoroalkyl substance (PFAS) has been linked to many adverse health outcomes including reduced fetal growth. However, limited studies have characterized the exposures and related outcomes among pregnant African American women, who are particularly at-risk for increased environmental exposures and adverse birth outcomes. Furthermore, the biological mechanisms linking PFAS exposure to fetal growth have not yet been elucidated. Thus, four study aims were developed to fill these research gaps in an African American birth cohort in Atlanta, Georgia. Aim 1 quantified 14 serum PFAS concentrations and evaluated their predictors. Aim 2 investigated the associations of PFAS with fetal growth outcomes and preterm delivery. To explore the biological mechanisms, Aim 3 examined the associations between serum PFAS and vitamin D biomarker concentrations and Aim 4 utilized high-resolution metabolomics coupling with a meet-in-a-middle approach to identify biological pathways and intermediate biomarkers associated with both PFAS concentrations and fetal growth outcomes.


In Aim 1, we found that PFAS exposures are ubiquitous among participants with > 95% detection frequencies in perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA). PFHxS concentrations in this cohort were higher when compared to the matched U.S. population. Several predictors, including education, sampling year, parity, BMI, tobacco and marijuana use, age of house, drinking water source, and cosmetic use, were significantly associated with PFAS levels. In Aim 2, PFNA and PFOA levels were significantly associated with odds of small-for-gestational age with the same directionality across most fetal growth outcomes. Aim 3 suggested that individual PFAS and PFAS mixtures may affect vitamin D biomarker concentrations, and some associations were modified by fetal sex. Furthermore, Aim 4 identified 10 metabolites and 21 metabolic pathways associated with both PFAS levels and fetal growth endpoints, and the results were closely related to the perturbations of amino acid, lipid and fatty acid, bile acid, uric acid, and androgenic hormone metabolisms.


This dissertation demonstrated that PFAS exposures are ubiquitous and may contribute to health disparities in fetal growth in this cohort. The identified biological pathways show potentials for future studies to develop early detection and intervention for PFAS-induced fetal growth restriction. 

Table of Contents

Chapter 1. Introduction. 1

Dissertation Aims. 5

Reference. 7

Chapter 2. PFAS Exposure Distribution and Predictors. 13

Abstract. 14

Introduction. 15

Materials and Methods. 16

Results. 21

Discussion. 23

Conclusions. 28

Figures and Tables. 30

Supplementary. 38

Reference. 43

Chapter 3. PFAS and Fetal Growth. 52

Abstract. 53

Introduction. 54

Materials and Methods. 55

Results. 60

Discussion. 62

Conclusion. 66

Figures and Tables. 67

Supplementary. 72

Reference. 83

Chapter 4. PFAS and Vitamin D. 91

Abstract. 92

Introduction. 93

Materials and Methods. 95

Results. 101

Discussion. 104

Conclusions. 109

Figures and Tables. 110

Supplementary. 115

Reference. 132

Chapter 5. PFAS, Metabolome, and Fetal Growth. 140

Abstract. 141

Introduction. 143

Materials and Methods. 144

Results. 151

Discussion. 154

Conclusions. 163

Figures and Tables. 164

Supplementary. 171

Reference. 182

Chapter 6. Conclusions. 193

Reference. 197

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