Prenatal Epigenetics: Trauma and Outcomes of Labor Dysfunction

项目总结 美国在产妇保健方面的支出比其他任何高收入国家都要多，但 严重的孕产妇发病率和死亡率。在其他高收入国家中，美国是最糟糕的 孕产妇发病率和死亡率。此外，在严重的孕产妇发病率方面也存在很大的差异。 死亡率，美国黑人孕妇比白人更有可能经历严重的 孕产妇发病率和死亡率。怀孕的黑人也不成比例地受到累积生活的影响 创伤，这是一种生命过程中的社会健康决定因素(SDoH)，与围产期不良密切相关 结果。在黑人分娩人群中，创伤与不良妊娠结局之间的一个很大程度上未被探索的联系 是生理系统中的表观遗传变化，对分娩和分娩以及人类来说都是不可或缺的 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，都已注意到有相关的变化 与创伤接触，并在分娩过程中发挥作用。此NRSA奖学金的目的是利用 通过表观基因组宽评估创伤对分娩结局的影响的适应的恒定负荷模型 DNA甲基化的关联性研究及其与分娩结局的关系。我们将利用 已经从两个预期队列中收集了生物样本和调查数据(R011NR019254：PI 尼科尔·卡尔森博士和R01MH115174：PI瓦西利基·米霍普洛斯博士) 地理区域。我们计划评估妊娠早期报告的累积生活创伤是否与 有劳动功能障碍，包括产程过长和非计划剖宫产。我们理论上认为创伤- 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 接触分娩结果，从而为这一人群优化围产期护理提供洞察力 减少劳动成果中的种族不平等。该项目还包括一项全面的培训计划 为了培养一名护士助产士临床医生成为一名具有表观遗传学专业知识的独立研究科学家， 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.