The Role of Vitamin D in Hypertensive Disorders in Pregnancy and Gene Expression in an African American Cohort Restricted; Files Only

Jordan, Sheila (Spring 2022)

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Background: Vitamin D is a steroid hormone that has multiple functions in the establishment and maintenance of a viable pregnancy. Vitamin D deficiency is prevalent across the globe and is especially pronounced among African American (AA) women in the United States. Previous research exploring vitamin D deficiency in pregnancy has shown mixed results. Much of this research has relied solely on total 25(OH)D as a marker of vitamin D status even though recent evidence shows that free 25-hydroxyvitamin D may a more reliable marker during pregnancy. The goal of this study was to examine the role of vitamin D, using both free and total 25(OH)D measures, in pregnancy looking specifically at hypertensive disorders in pregnancy (HDP) and gene expression.

Methods: Nested in a larger longitudinal, prospective cohort study data was collected from 207 AA women. Participants self-identified as AA and were recruited at 8-14 weeks gestation of a singleton pregnancy from the Grady Hospital and Emory Midtown prenatal clinics in Atlanta, Georgia.

Results: The relationship between vitamin D and HDP was evaluated with a multinomial logistic regression model. Results from this analysis showed that those with total 25(OH)D deficiency in the first trimester were at increased risk for HDP (aOR 4.93, 95% CI 1.94 – 12.55, p<0.001). Free 25(OH)D in the first trimester was associated with a decreased risk for preeclampsia (aOR 0.56, 95%CI 0.32-0.95, p=0.037). The relationship between vitamin D and gene expression during pregnancy was investigated with a linear mixed-effects model. This study identified 121 genes whose expression levels associated with total 25(OH)D at a false discovery rate of less 5%. Genes who expression increased over pregnancy were associated with cell differentiation and proliferation, placental development, and immune function.

Conclusions: Further characterizing the differences in the transcriptome throughout gestation according to vitamin D concentrations may help identify genes and processes that can uncover the physiologic links between vitamin D and pregnancy outcomes. Efforts to improve vitamin D status among African Americans may potentially improve maternal health outcomes and help close the gap on the disparity observed in this population.

Table of Contents

Chapter 1: Introduction 1

Manuscript 1: The Role of Vitamin D in Pregnancy 43

Manuscript 2: Vitamin D and Hypertensive Disorders in Pregnancy 81

Manuscript 3: Vitamin D and Gene Expression in Pregnancy 112

Chapter 5: Dissertation Conclusion 136

Appendix A 168

Appendix B 175

Appendix C 181

List of Tables and Figures

Table 1.1 Biological and Questionnaire Data Collection 20

Table 2.1 Participant Characteristics According to Pregnancy Outcome Category 91

Table 2.2 Vitamin D Concentration and Status According to Pregnancy Outcome Category 93

Table 2.3 Adjusted Odds of Hypertensive Disorders in Pregnancy According to Vitamin D Status 96

Figure 2.1 Relationship between Free25(OH)D Vitamin D vs Total 25(OH)D at Visit 1 94

Table 3.1 Demographic and Clinical Characteristics of Sample 120

Table 3.2 Total & Free 25(OH)D of Participants 121

Figure 3.1 Volcano Plot of gene expression differences 123

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