Preterm Delivery and Maternal Cardiovascular Disease Risk

摘要本应用程序的目的是确定：1)将早产与晚年产妇心血管疾病风险联系起来的机制；2)早产妇女亚组，她们可能受益于早期跟踪和干预，以减少未来的心血管疾病（CVD）。在美国，早产（PTD）的发生率为12.5%，而且这一比例还在不断上升。与足月分娩的妇女相比，早产的妇女患心血管疾病的风险更高，但与这些情况相关的机制尚不清楚。产后抑郁症是一种异质性的结果，早产妇女的亚群可能有不同的后期生活后遗症。我们假设怀孕揭示了心血管疾病的易感，并且炎症、血脂异常和血栓形成在怀孕期间会聚到一起，损害了胎盘和/或早产妇女的母体血管完整性。因此，患有PTD的妇女，特别是那些有胎盘血管病变的妇女，在产后会有动脉粥样硬化的特征和动脉粥样硬化的早期证据。我们建议对参加妊娠结局和社区健康（育儿袋）研究的妇女进行随访研究，这是一项1998-2004年纳入的前瞻性队列研究，旨在研究PTD的途径。在入组时采集血液样本，孕15-27周。产前，分娩和分娩记录提取和胎盘检查在一个单一的胎盘病理学家的盲法。我们计划在此框架的基础上，研究有PTD和无PTD女性的心血管特征，并在参与育儿袋研究后6-11年确定与心血管风险证据相关的PTD亚型。我们将招募大约896名女性（513名白人/其他人种和383名非裔美国人）；217人早产，679人足月分娩。我们将收集问卷调查数据和动脉粥样硬化概况的测量，如人体测量（身高、体重、腰围）、血压、炎症标志物、脂质和血栓形成因子的血液水平。此外，我们将通过颈动脉超声扫描（颈动脉内膜-内侧厚度）评估动脉粥样硬化的早期证据。我们的目的是比较随访时的结果。即足月分娩妇女的动脉粥样硬化概况和早期动脉粥样硬化：1)既往有PTD的妇女；2)根据临床情况和胎盘病理分组的PTD亚型妇女；3)根据妊娠中期血脂异常和炎症生物标志物水平分组的PTD亚型妇女。此外，我们将研究目的1中的关联是否会受到社会经济地位、种族或母亲抑郁/痛苦等因素的影响。揭示PTD与母体CVD风险之间联系的途径的研究可以为这两种医学问题提供新的干预策略，并有助于在疾病过程的早期识别女性，此时干预可能会延迟或预防疾病的发生。

DESCRIPTION (provided by investigator): Preterm delivery and maternal cardiovascular disease risk Abstract The objective of this applications is to identify: 1) mechanisms that link preterm birth to later life maternal cardiovascular risk; and 2) subgroups of women who deliver preterm and might benefit from early tracking and interventions to reduce future cardiovascular disease (CVD). Preterm delivery (PTD) occurs in 12.5 percent of pregnancies in the U.S., and rates are increasing. Women who have delivered a preterm infant have excess risk of developing CVD compared to those with term deliveries, but mechanisms relating these conditions are not understood. PTD is a heterogenous outcome, and it is likely that subsets of women who deliver preterm may have different later life sequelae. We hypothesize that pregnancy unmasks a predisposition to CVD and that inflammation, dyslipidemia and thrombogenesis converge in pregnancy to compromise placentation and/or maternal vascular integrity among a subset of women who deliver preterm. Therefore women with PTD, particularly those with placental vascular lesions, will have an atherogenic profile post partum and early evidence of atherosclerosis. We propose a follow-up study of women enrolled in the Pregnancy Outcomes and Community Health (POUCH) Study, a prospective cohort enrolled from 1998-2004 designed to examine pathways to PTD. Blood samples were collected at enrollment, 15-27 weeks' gestation. Prenatal, labor and delivery records were abstracted and placentas were examined in a blinded fashion by a single placental pathologist. We plan to build on this framework by studying the cardiovascular profile among women with and without PTD and by identifying subtypes of PTD associated with evidence of cardiovascular risk at 6-11 years after POUCH Study participation. We will enroll approximately 896 women (513 white/other and 383 African Americans); 217 who delivered preterm and 679 who delivered at term during the POUCH Study. We will collect questionnaire data and measures of an atherogenic profile such as anthropometrics (height, weight, waist circumference), blood pressure, and blood levels of inflammatory markers, lipids, and thrombogenic factors. In addition we will assess early evidence of atherosclerosis via carotid ultrasound scans (carotid intimal- medial thickness). Our aims will be to compare the outcome measures at follow-up. i.e. atherogenic profile and early atherosclerosis among women with term births and: 1) women with a prior PTD; 2) women with PTD subtypes grouped by clinical circumstance and placental pathology; and 3) women with PTD subtypes grouped by levels of dyslipidemia and inflammation biomarkers in mid-pregnancy. In addition we will examine whether associations in Aim 1 might be modified by factors such as socioeconomic status, race, or maternal depression/distress. Studies that uncover pathways linking PTD to maternal CVD risk can lead to new intervention strategies for both of these medical problems, and help to identify women very early in the disease process when intervention may delay or prevent onset of disease. PUBLIC HEALTH RELEVANCE: Recent evidence indicates that women who deliver preterm may be at increased risk of CVD later in life, but the nature of this connection is poorly understood and remains a 'black box.' In this study we have a unique opportunity to assess the atherogenic profile and early evidence of atherosclerosis in a cohort of women for whom we have detailed pregnancy data (biomarkers, placental pathology) as part of an earlier study on preterm delivery. This proposed follow-up study will lead to a more in-depth understanding of the pathways that connect preterm delivery and later CVD risk, and will aid in targeting women at high risk for CVD and selecting appropriate early interventions.