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

项目摘要 该提案概述了一个为期3年的博士后奖学金，旨在提供跨学科的培训， 在主要研究型大学从事独立研究工作。申请人的兴趣包括理解 压力体验影响围产期结局的生物学机制。先前的研究 反复表明，在怀孕期间经历压力性生活事件的女性患乳腺癌的风险增加。 不良出生结局，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知之甚少。申请人的长期研究目标是 通过跨学科研究来阐明这些机制。因此，她提议与 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， 这些不同领域的专业知识，他们已经在NIH资助的两个主要项目上进行合作。研究 该计划包括三个目标，使用不同的策略来解决压力性生活事件之间的关系 妊娠期间，母体炎症，胎盘功能和分娩结局。目标1调查链接 生活事件和不良出生结果之间的关系，包括早产和胎儿生长不良。调解 还将探索母体血清中的炎性标志物。目标2评估暗杀的影响 总统约翰·F。肯尼迪，一个压力事件，许多美国人，对出生结果和检查 通过胎盘炎症和血管病变介导。为了获得更有力的证据进行因果推理，这 还将在暴露不一致的兄弟姐妹中检查关系。目的3研究细胞机制， 并考虑生活事件是否促进母体免疫细胞的胎盘浸润。此外该 所有三个目标中与怀孕相关的事件的已知时间使得能够对关键窗口进行调查。 总的来说，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 制定干预措施。此外，了解压力如何影响怀孕越来越重要， 研究报告指出，代际效应可能使后代更容易受到不利影响。 这项研究是一个更广泛的培训计划的一部分，将补充申请人的背景， 围产期流行病学通过这种培训，申请人将（1）发展概念化方面的专业知识 和测量的关键结构在健康心理学，（2）获得接触的临床管理， 不良妊娠结局，和（3）发展评估胎盘病理学的实验室工具的专业知识。 为了实现这些目标，申请人将完成相关的课程，并将获得实践培训， 与她的共同赞助人合作，他们是这些领域的专家。此外，申请人将参加 专业发展活动，包括参加会议和研究道德和赠款培训 写作这种培训，结合申请人的背景，将为她作为PI的职业生涯做好准备 开展多学科研究，调查产妇压力如何影响妊娠结果。

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.