Placental Vascular Compromise and Preterm Delivery

描述（由申请人提供）：有实质性的兴趣， 确定早产（PTD）的病因。尽管做了很多努力， 原因仍然难以捉摸，也不存在有效的预防措施。 通过炎症、血栓形成或 动脉粥样硬化是早产的一个生物学上合理的原因， 充分探索。我们建议通过进行一次 UPVC的前瞻性流行病学研究， PTD的已知风险因素。胎盘组织病理学检查和 将进行基板的形态测定分析，以评估 胎盘血管。我们将探索这种新的，可能的先例， 妥协，血脂异常和胰岛素抵抗，使用核磁共振成像， 脂质亚类和空腹胰岛素-葡萄糖比率的共振分析。 考虑到子宫胎盘血管系统的不可及性， 妊娠中期，我们将使用UPVC的非侵入性措施， 子宫动脉多普勒血流速度测定和母体血清甲胎蛋白 间接评估血管功能。此外，我们将认真 评估烟草和可卡因的使用，营养和阴道微生物菌群的变化 在我们的队列中。这些数据将使我们能够彻底评估UPVC是否 构成PTD的独特病因学途径，并有助于识别 可改变的风险因素。我们将利用队列和病例队列技术， 在我们目前的研究中得到了完善，以回答这些问题。血液、尿液和 在15 - 20周和24 - 29周之间收集阴道液两次 怀孕几周。头发将在分娩后收集。所有受试者将 完成两次电话访谈和两份自填问卷 关于各种行为，饮食摄入，身体活动， 社会心理压力源胎盘将在分娩时收集， 组织病理学分析将由有经验的围产期专家完成。 病例和非病例亚组的病理学家。核磁共振 将进行脂蛋白亚类的测量以评估血脂异常。 将从空腹血样中测量胰岛素葡萄糖比值。我们预计 入组一组1800名妇女，其中250名早产， 选择非病例亚组（n=500）。我们将分析 UPVC和PTD使用逻辑回归。考虑到1）研究的规模，2） 对胎盘进行彻底的组织病理学评估，3）广泛的问卷调查 数据，4）暴露于细菌性阴道病的生物标志物，胰岛素 抵抗，血脂异常和可卡因使用，和5）仔细评估 潜在的混杂因素，这项研究有望显着推进我们的 了解UPVC在PTD病因学中的潜在作用。

DESCRIPTION (provided by applicant): There is substantial interest in determining the etiology of preterm delivery (PTD). Despite much effort, the cause remains elusive and effective prevention measures do not exist. Uteroplacental vascular compromise (UPVC) via inflammation, thrombosis, or atherosis is a biologically plausible cause of preterm delivery, albeit not adequately explored. We propose to test his hypothesis by conducting a prospective, epidemiologic study of UPVC and by integrating information about known risk factors for PTD. Placental histopathologic examination and morphometric analysis of the basal plate will be done to assess compromise of placental vessels. We will explore novel, possible antecedents of such compromise, dyslipidemia and insulin resistance, using nuclear magnetic resonance analysis of lipid subclasses and fasting insulin-glucose ratios. Given the inaccessibility of the uteroplacental vasculature in ongoing gestations at midpregnancy, we will utilize non-invasive measures of UPVC, Doppler velocimetry of the uterine artery, and maternal serum alpha fetoprotein to indirectly evaluate vascular function. In addition, we will carefully evaluate tobacco and cocaine use, nutrition, and changes in vaginal microflora within our cohort. The data will enable us to thoroughly assess whether UPVC constitutes a distinct etiologic pathway for PTD and help to identify modifiable risk factors. We will utilize cohort and case-cohort techniques, refined in our present research, to answer these questions. Blood, urine and vaginal fluid are collected twice between 15 and 20 weeks and between 24 and 29 weeks gestation. Hair will be collected after delivery. All subjects will complete two telephone interviews and two self administered questionnaires regarding various behaviors, dietary intake, physical activity, and psychosocial stressors. Placentas will be collected at the time of delivery and histopathologic analysis will be completed by an experienced perinatal pathologist for cases and a non-case subgroup. Nuclear magnetic resonance measurement of lipoprotein subclasses will be done to assess dyslipidemia. Insulin glucose ratios will be measured from fasting blood samples. We expect to enroll a cohort of 1800 women with 250 preterm deliveries and a randomly selected non-case subgroup (n=500). We will analyze the relationship between UPVC and PTD using logistic regression. Given 1) the size of the study, 2) thorough histopathologic assessment of the placenta, 3) extensive questionnaire data, 4) biologic markers of exposure to bacterial vaginosis, insulin resistance, dyslipidemia, and cocaine use, and 5) the careful assessment of potential confounding factors, this study promises to markedly advance our knowledge of the potential role of UPVC in the etiology of PTD.