Placental contributions to disparities in offspring cardiovascular health across the life course

项目摘要/摘要 在心血管疾病(CVD)方面，种族和社会经济差异显著且持续存在。 美国。越来越多的证据表明，围产期是代际的关键窗口。 心血管疾病差异的传播。早产儿或小于胎龄儿患心血管疾病的风险更大 成年期的发病率和死亡率。此外，早产和小于胎龄儿的差异 反映在心血管疾病中观察到的情况。作为母胎界面的器官，负责调节胎儿 从发育的角度来看，胎盘是了解差异代际传播的关键。一致 根据这一观点，研究报告称，胎盘尺寸减小与后代心血管疾病有关。 胎盘大小是功能的粗略衡量标准。改善胎盘功能评估的技术包括 血管和炎性病变的组织学评估和图像分析评估血管结构。 利用这些强大的胎盘测量手段进行的研究具有重要的科学和临床意义。 从科学上讲，它们提供了关于心血管疾病风险孕期起源的更深层次的机械性见解，这可以为 妊娠干预措施的发展。在临床上，它们有可能通过以下方式缓解心血管疾病的差异 改进风险分层和告知处理方法。因此，这项提案的目标是 了解导致后代种族和社会经济差异的胎盘机制 整个生命过程中的心血管健康。评估胎盘测量与子代的关系 心血管健康将通过启动儿科心血管随访来实现 应激妊娠与健康研究(SPAH；N=150)。此外，两个互补的队列与常规 将利用胎盘数据收集和纵向跟踪：合作围产期项目(CPP； N=43,837)和雅芳亲子纵向研究(ALSPAC；N=799)。这些队伍将成为 用来解决三个目标。目的1：确定胎盘功能障碍是否影响心血管疾病的危险因素 通过(A)评估胎盘病变和血管结构以及(B)利用兄弟姐妹 对照设计以控制父母和环境的混杂。目标2：确定是否 胎盘病变与心血管结构、功能和心血管危险因素的差异有关 青春期和青壮年。目的3：确定胎盘病变是否与 成年期子代过早心血管病死亡率的差异。作为一名围产期流行病学家，这一奖项将有所帮助 我将我的专业知识扩展到评估后代的心血管结果。通过进行的过程 本次研究，我将获得导师的指导和培训，在纵向研究中，全面研究胎盘 评估，以及整个生命过程中的心血管健康。总的来说，这项研究和培训将装备 我有必要的专业知识来发展一项独特的研究事业，研究胎盘对 子代心血管健康在一生中的差异。

PROJECT SUMMARY/ABSTRACT There are significant and persistent racial and socioeconomic disparities in cardiovascular disease (CVD) in the United States. Growing evidence indicates that the perinatal period is a critical window for intergenerational transmission of CVD disparities. Infants born preterm or small for gestational age are at greater risk of CVD morbidity and mortality in adulthood. Further, disparities in preterm birth and small for gestational age infant mirror those observed in CVD. As the organ at the maternal-fetal interface responsible for regulating fetal development, the placenta is the key to understanding intergenerational transmission of disparities. Consistent with this view, studies have reported that reduced placental size is associated with offspring CVD, though placental size is a crude measure of function. Techniques to improve assessment of placental function include histologic evaluation for vascular and inflammatory lesions and image analysis to evaluate vascular structure. Studies leveraging these robust placental measures have important scientific and clinical implications. Scientifically, they yield deeper mechanistic insights about the gestational origins of CVD risk, which can inform development of gestational interventions. Clinically, they have the potential to mitigate CVD disparities by improving risk stratification and informing treatment approaches. Accordingly, the goal of this proposal is to understand the placental mechanisms underlying racial and socioeconomic disparities in offspring cardiovascular health across the life course. Evaluating placental measures in relation to offspring cardiovascular health will be accomplished by initiating pediatric cardiovascular follow up in offspring from the Stress Pregnancy and Health study (SPAH; N=150). In addition, two complementary cohorts with routine placental data collection and longitudinal follow up will be leveraged: the Collaborative Perinatal Project (CPP; N=43,837) and the Avon Longitudinal Study of Parents and Children (ALSPAC; N=799). These cohorts will be used to address three aims. Aim 1: To determine whether placental dysfunction impacts CVD risk factor disparities in childhood by (a) evaluating placental lesions and vascular structure and (b) leveraging a sibling comparison design to control for parental and environmental confounding. Aim 2: To determine whether placental lesions are associated with disparities in cardiovascular structure, function, and CVD risk factors in adolescence and young adulthood. Aim 3: To determine whether placental lesions are associated with disparities in offspring premature CVD mortality in adulthood. As a perinatal epidemiologist, this award will help me extend my expertise to evaluating offspring cardiovascular outcomes. Through the process of conducting this research, I will obtain mentorship and training in leading longitudinal studies, comprehensive placental evaluation, and cardiovascular health across the life course. Collectively, this research and training will equip me with the expertise necessary to develop a unique research career investigating placental contributions to disparities in offspring cardiovascular health across the life course.