Prenatal Epigenetics: Trauma and Outcomes of Labor Dysfunction

项目摘要 美国在产妇护理方面的支出比任何其他高收入国家都要多，但产妇死亡率却在上升。 产妇发病率和死亡率很高。在其他高收入国家中，美国在以下方面排名最差： 产妇发病率和死亡率。此外，在严重的孕产妇发病率方面， 和死亡率，美国的黑人孕妇比白色人更有可能经历严重的 产妇发病率和死亡率。怀孕的黑人也不成比例地受到累积寿命的影响 创伤，这是一个生命过程的社会健康决定因素（SDoH）与围产期不良密切相关， 成果。在黑人分娩人群中，创伤和不良妊娠结局之间的一个基本未被探索的联系 是生理系统中的表观遗传变化，这些变化与分娩和分娩都是不可或缺的， 对创伤的反应。其中包括下丘脑-垂体-肾上腺轴（HPA轴）、催产素能 系统和炎症反应系统功能，这些都被注意到有相关的变化 在分娩过程中发挥作用。这个NRSA奖学金的目的是利用一个 通过表观全基因组，调整适应性负荷模型，以评估创伤对分娩结局的影响 DNA甲基化及其与分娩结局的相关性研究。我们将利用 已经从两个前瞻性队列中收集了生物样本和调查数据（R 011 NR 019254：PI 博士Nicole Carlson和R 01 MH 115174：PI Vasiliki Michopoulos博士）的黑人孕妇生活在同一个 地理区域。我们计划评估在怀孕早期报告的累积性生活创伤是否与 产程障碍，包括产程时间长和计划外剖宫产。我们认为创伤- 相关的表观遗传变化可能提供了连接黑人孕妇创伤的缺失环节 暴露与分娩结果，从而提供了深入了解如何优化围产期护理，为这一人口， 减少劳动结果中的种族不平等。该项目还包括一个全面的培训计划， 准备护士助产士临床医生是一个独立的研究科学家与专业知识在表观遗传学， 创伤和围产期差异研究。

PROJECT SUMMARY The United States spends more on maternity care than any other high-income country yet has rising rates of severe maternal morbidity and mortality. Among other high-income countries, the U.S. ranks as the worst in maternal morbidity and mortality rates. Moreover, there are significant disparities in severe maternal morbidity and mortality, with Black pregnant people in the U.S. being more likely than white people to experience severe maternal morbidity and mortality. Pregnant Black people are also disproportionately impacted by cumulative life trauma, which is a life course social determinant of health (SDoH) strongly associated with poor perinatal outcomes. One largely unexplored link between trauma and poor pregnancy outcomes in Black birthing people is epigenetic changes in physiologic systems that are integral to both labor initiation and parturition and human response to trauma. Among these are the hypothalamic-pituitary-adrenal axis (HPA-axis), oxytocinergic system, and inflammatory response system function which have all been noted to have changes associated with trauma exposure and play a role in parturition. The purpose of this NRSA fellowship is to utilize an adapted allostatic load model to evaluate the effects of trauma on labor outcomes, through an epigenome wide association study of DNA methylation, and its subsequent association with labor outcomes. We will leverage biologic samples and survey data already being collected from two prospective cohorts (R011NR019254: PI Dr. Nicole Carlson and R01MH115174: PI Dr. Vasiliki Michopoulos) of Black pregnant people living in the same geographic area. We plan to evaluate if cumulative life trauma, as reported in early pregnancy, is associated with labor dysfunction, including long labor duration and unplanned cesarean section. We theorize that trauma- associated epigenetic changes may provide a missing link connecting Black pregnant people’s trauma exposure with labor outcomes, thus providing insight into ways to optimize perinatal care for this population to reduce racial inequities in labor outcomes. This project also includes a comprehensive training plan designed to prepare a nurse-midwife clinician to be an independent research scientist with expertise in epigenetics, trauma, and perinatal disparities research.