Prenatal Epigenetics: Trauma and Outcomes of Labor Dysfunction Restricted; Files Only
Britt, Abby (Summer 2025)
Abstract
Black pregnant people are disproportionately affected by trauma exposure, post-traumatic stress disorder (PTSD), and maternal morbidity and mortality. PTSD has been associated with increased risk for maternal morbidity and mortality; however, little is known about the physiologic mechanisms by which PTSD may contribute to poor perinatal outcomes. PTSD is associated with dysregulation of stress physiology systems, including the hypothalamic-pituitary- adrenal axis, the oxytocin system, and immunologic function which are integral to labor progress. Labor dysfunction, defined as labor dystocia and unplanned cesarean birth, is a primary contributor to maternal morbidity and mortality. Thus, in the first paper of this dissertation I examined associations among childhood maltreatment, labor duration, and synthetic oxytocin requirements for vaginal birth in a sample of Black birthing people. In that sample, among those who had induced labor, associations were found between childhood emotional and physical abuse and labor duration in adjusted models. Additionally, there were associations between childhood physical abuse with higher intrapartum synthetic oxytocin dose, duration, and mean dose per hour. In the second chapter, in a sample of Black pregnant people getting prenatal care at a birth center or hospital, I evaluated relationships among childhood maltreatment, life course trauma exposure, PTSD symptoms and labor dystocia and unplanned cesarean birth. In the total induction of labor sample, PTSD symptoms and provisional PTSD were associated with labor dystocia but not unplanned cesarean birth. In the third paper, a subset of participants from the second paper who gave prenatal blood samples for epigenetic analyses were evaluated. Associations were found between PTSD symptom total score and DNA methylation at cg16373697 in the SLC14A2 gene, which is involved with renal function and hypertension. Associations were also found between labor dystocia and DNA methylation at cg18718657 in the FKBP2 gene, which is involved in complement cascade and proinsulin protein folding and trafficking. CpG sites associated (P<.05) with PTSD symptom score were 2.3 times more likely to also be associated with labor dystocia. Overall, the results in this dissertation highlights relationships among childhood maltreatment, trauma exposure, PTSD, differences in DNA methylation, and labor dystocia in multiple cohorts of Black pregnant people.
Table of Contents
Table of Contents
CHAPTER 1: INTRODUCTION: TRAUMA, POST TRAUMATIC STRESS DISORDER, AND LABOR DYSFUNCTION 1
Context and Authors’ Contribution 1
Trauma as a Social Determinant of Health: Prevalence and Health Outcomes 2
Post Traumatic Stress Disorder 2
Disparities in Trauma Exposure, Post Traumatic Stress Disorder, and Maternal Morbidity and Mortality 3
Labor Dysfunction 4
Trauma and Labor Dysfunction Outcomes 4
Influence of Maternal Trauma Exposure from Adulthood on Labor Dystocia and Unplanned Cesarean Birth 5
Influence of Maternal Trauma Exposure from Childhood on Labor Dystocia and Unplanned Cesarean Birth 9
Trauma, Epigenetics, and Pregnancy 18
Physiology of Normal Parturition in Humans 19
Preparation and Labor Initiation 19
Physiology of Uterine Activity and Endurance in Labor 20
Trauma, Stress, and Immunologic Dysregulation in Pregnancy and Labor 23
Trauma, Stress and Oxytocin System in Pregnancy and Labor 25
Trauma and Stress Related Disorders and HPA-Axis in Pregnancy 28
Purpose 30
Conceptual Framework: Trauma, Allostatic Load, and Perinatal Outcomes 31
Specific Aims 31
Summary 33
CHAPTER 2: CHILDHOOD MALTREATMENT, LABOR DURATION, AND INTRAPARTUM SYNTHETIC OXYTOCIN DOSE AND DURATION: A POTENTIAL OXYTOCIN-LINKED CONTRIBUTOR TO LABOR OUTCOMES IN BLACK BIRTHING PEOPLE 44
Context, Authors’ Contribution, And Acknowledgement of Reproduction 44
Abstract 45
INTRODUCTION 46
Childhood Trauma and the Oxytocin System 47
Childhood Trauma and Labor Duration 48
METHODS 49
Results 54
Participants Demographics 54
Associations Between Childhood Maltreatment and Labor Duration 56
Clinical Interpretation 58
Associations Between Childhood Maltreatment and Intrapartum Synthetic Oxytocin Requirements 60
DISCUSSION 62
Strengths, Limitations, and Future Directions 63
CONCLUSION 65
CHAPTER 3: TRAUMA EXPOSURE, POST TRAUMATIC STRESS DISORDER AND OUTCOMES OF LABOR DYSFUNCTION IN A SAMPLE OF BLACK PREGNANT PEOPLE 70
Context and Authors’ Contribution 70
Abstract 71
Maternal Trauma Exposure and Labor Dystocia 73
Maternal Trauma Exposure and Unplanned Cesarean 76
Trauma Exposure and Labor Dysfunction Outcomes in Black Pregnant Populations in the United States 80
Methods 81
Results 87
Participant Demographics 87
Associations Between TEI-LEC Harmonized Scale, Childhood Trauma Questionnaire, and PCL-5 Score and Labor Dysfunction Outcomes in the Total Sample and Stratified by Mode of Labor Onset 91
Associations Between PTSD, Trauma Exposure, and Labor Dysfunction Outcomes in the Total Sample Stratified by Prenatal Care Site and Mode of Labor Onset 95
Discussion 98
Strengths, Limitations, and Future Directions 100
Conclusion 103
CHAPTER 4: RELATIONSHIPS BETWEEN PTSD, DNA METHYLATION AND LABOR DYSFUNCTION OUTCOMES IN A COHORT OF BLACK PREGNANT PEOPLE 111
Context and Authors’ Contribution 111
Abstract 112
Introduction 113
Methods 116
Results 122
Trauma Exposure, Provisional PTSD and Differential DNA Methylation 124
Post Traumatic Stress Disorder Symptoms Associated with Methylation at cg16373697 in SLC14A2 Gene 124
Methylation at cg16373697 in SLC14A2 Gene Associated with Hypertensive Disorders of Pregnancy 126
Labor Dystocia Associated with Methylation in cg18718657 in FKBP2 Gene 126
Enrichment Test for CpGs Associated with PCL-5 Score and Labor Dystocia 128
Relationships Between PCL-5 Total Score, Epigenetic Biomarker Proxies, and Metabolic Risk Score 128
Relationships Between DNAm at cg18718657, Labor Dystocia Metabolic Risk Score, Epigenetic Biomarker Proxies, and Metabolic Risk Score 130
Discussion 132
Strengths, Limitations, and Future Directions 135
CHAPTER 5: SYNTHESIS AND FUTURE DIRECTIONS 146
Context and Authors’ Contribution 146
Introduction 147
Theoretical Framework 147
Summary of the Study Findings 148
Contributions to the Literature 155
Study Limitations and Strengths 157
Implications for Clinical Practice and Future Research 158
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File download under embargo until 21 August 2031 | 2025-06-12 15:27:53 -0400 | File download under embargo until 21 August 2031 |
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