Maternal psychological stress, adverse birth outcomes, and the role of inflammatory mediators in the placenta

项目摘要 这项建议概述了为期3年的博士后奖学金，旨在为 在一所主要研究型大学的独立研究生涯。申请人的利益涉及了解 应激经历影响围产期结局的生物学机制。之前的研究已经 反复表明，在怀孕期间经历过压力生活事件的女性患上 不良分娩结局，包括早产和胎儿发育异常。然而，生物途径 这种关系的基础仍然鲜为人知。申请者的长期研究目标是 通过跨学科研究阐明这些机制。因此，她提议与 在健康心理学、胎儿发育和胎盘生物学方面的培训，由一组导师监督， 他们已经在NIH资助的两个主要项目上进行了合作。这项研究 计划包括三个目标，它们使用不同的策略来处理压力生活事件之间的关系 孕期、母体炎症、胎盘功能和分娩结局。目标1调查链接 生活事件和不良分娩结果之间的关系，包括早产和胎儿发育不良。调解人 还将探索母体血清中的炎症标志物。目标2评估了暗杀的影响 对许多美国人来说，约翰·F·肯尼迪总统的出生结局是一件令人紧张的事情，并检查了 胎盘炎症和血管病变的调解。为了为因果推论获得更有力的证据，这 关系也将在不和谐的兄弟姐妹中进行检查。目标3研究细胞机制， 并考虑生活事件是否有助于胎盘对母体免疫细胞的渗透。此外， 所有三个目标中与怀孕有关的事件的已知时间安排使关键窗口的调查成为可能。 总而言之，这些结果将有助于阐明压力如何影响妊娠结局，这可能是有用的 用于制定干预措施。此外，了解压力如何影响怀孕越来越重要，因为 研究报告称，代际影响可能会使后代更容易受到不良后果的影响。 这项研究是一个更广泛的培训计划的一部分，该计划将补充申请者在 围产期流行病学。通过这次培训，申请者将(1)发展概念化方面的专门知识 和测量健康心理学的关键结构，(2)接触临床管理 不良妊娠结局，以及(3)开发评估胎盘病理的实验室工具方面的专业知识。 为了实现这些目标，申请者将完成相关课程，并将通过以下方式获得实践培训 与她的共同赞助人合作，他们都是这些领域的专家。此外，申请者还将参加 专业发展活动，包括参加会议以及研究道德和补助金方面的培训 写作。这一培训，结合申请者的背景，将为她成为私人投资公司的职业生涯做好准备 进行多学科研究，以调查母亲压力如何影响妊娠结局。

Project Summary This proposal outlines a 3-year post-doctoral fellowship, designed to provide interdisciplinary training for an independent research career at a major research university. The applicant’s interests involve understanding the biological mechanisms by which stressful experiences affect perinatal outcomes. Previous research has repeatedly shown that women who experience stressful life events during pregnancy are at increased risk of adverse birth outcomes, including preterm birth and abnormal fetal growth. However, the biologic pathways that underlie this relationship continue to be poorly understood. The applicant’s long-term research goal is to clarify these mechanisms through interdisciplinary research. Accordingly, she proposes a fellowship with training in health psychology, fetal development, and placental biology, overseen by a team of mentors with expertise in these distinct fields, who are already collaborating on two major NIH-funded projects. The research plan includes three aims, which use different strategies to address the relationships among stressful life events during pregnancy, maternal inflammation, placental function, and birth outcomes. Aim 1 investigates links between life events and adverse birth outcomes, including preterm birth and poor fetal growth. Mediation by inflammatory markers in maternal serum will also be explored. Aim 2 evaluates the impact of the assassination of President John F. Kennedy, a stressful event for many Americans, on birth outcomes and examines mediation by placental inflammatory and vascular lesions. To gain stronger evidence for causal inference, this relationship will also be examined in siblings discordant for exposure. Aim 3 investigates cellular mechanisms, and considers whether life events facilitate placental infiltration of maternal immune cells. In addition, the known timing of the events relative to pregnancy in all three aims enables the investigation of critical windows. Collectively, the results will help to elucidate how stress may affect pregnancy outcomes, which may be useful for developing interventions. Further, understanding how stress impacts pregnancy is increasingly important as studies have reported intergenerational effects that may predispose future generations to adverse outcomes. The research is part of a broader training program that will supplement the applicant’s background in perinatal epidemiology. Through this training, the applicant will (1) develop expertise in the conceptualization and measurement of key constructs in health psychology, (2) gain exposure to the clinical management of adverse pregnancy outcomes, and (3) develop expertise in laboratory tools for evaluating placental pathology. To accomplish these goals, the applicant will complete relevant coursework and will gain hands-on training by working with her co-sponsors, who are experts in these areas. In addition, the applicant will participate in professional development activities, including conference participation and training in research ethics and grant writing. This training, in combination with the applicant’s background, will prepare her for career as a PI conducting multidisciplinary research to investigate how maternal stress affects pregnancy outcomes.