Preterm Birth in Nulliparous Women: An Understudied Population at Great Risk

描述（由申请人提供）：宾夕法尼亚大学卫生系统的妇产科反映了在临床和转化研究方面的卓越传统。母胎医学部的研究人员一直是这一传统的主要参与者，特别是在他们对与早产有关的遗传因素和环境暴露的研究方面。在本应用程序中，我们提供了宾夕法尼亚大学产科服务的两家医院的信息——宾夕法尼亚大学医院（HUP）和宾夕法尼亚医院（PAH）——这两家医院都是该网络建议的患者招募地点。本申请的具体目的是：1)为网络研究的设计提供咨询，包括协助指导委员会进行研究设计、样本量计算和统计分析，并选择最佳数据和样本收集方案；2)招收网络研究对象，为网络研究提供优质数据；3)进行超声研究，实验室分析，以及完成拟议研究所需的高通量基因组学和蛋白质组学分析；4)参与网络研究的分析与发表。HUP和PAH的联合交付量每年超过9,000个。两家医院的MFM医生共同承担临床责任，并在各种临床研究中有着丰富的合作记录。重要的是，该申请的首席研究员是早产研究基因组学和蛋白质组学网络分析核心的首席研究员，并将为拟议的早产网络带来有关研究设计，样本收集和分析技术（包括高通量研究）的重要专业知识。研究人员提出了一项前瞻性队列研究，其中产前超声结果（宫颈长度，子宫动脉多普勒血流），蛋白质生物标志物（循环血管生成因子，使用感兴趣细胞标记蛋白质的蛋白质组学技术）和转录组学分析将与临床结果和胎盘组织学结果相关。要验证的假设是，妊娠早期胎盘功能障碍的标志物将识别有早产风险的未生育妇女。

DESCRIPTION (provided by applicant): The University of Pennsylvania Health System's Department of Obstetrics and Gynecology reflects a long tradition of excellence in clinical and translational research. Investigators within the Division of Maternal-Fetal Medicine have been key participants in this tradition, particularly in their studies of genetic factors and environmental exposures that are associated with preterm birth. In this application, we provide information on the two hospitals that comprise the obstetric services at the University of Pennsylvania - the Hospital of the University of Pennsylvania (HUP) and Pennsylvania Hospital (PAH) - both of which are proposed sites of patient recruitment for the network. The specific aims of this application are: 1) to provide consultation on the design of network studies, which includes assisting the Steering Committee in study design, sample size calculations, and statistical analyses, and selecting optimal data and sample collection protocols; 2) to enroll subjects into network studies and to provide quality data for network studies; 3) to perform ultrasound studies, laboratory assays, and high-throughput genomics and proteomics assays required to complete proposed studies; and 4) to be involved in the analysis and publication of network studies. The combined delivery volume of HUP and PAH is over 9,000 per year. The MFM physicians at the two hospitals share clinical responsibilities and have a substantial track record for collaboration in various clinical studies. Importantly, the principal investigator for this application is the principal investigator of the Analytical Core for the Genomics and Proteomics Network for Preterm Birth Research and will bring significant expertise regarding study design, sample collection, and assay techniques (including high-throughput studies), to the proposed preterm birth network. The investigators propose a prospective cohort study in which prenatal ultrasound findings (cervical length, uterine artery Doppler flow), protein biomarkers (circulating angiogenic factors, proteomics techniques using labeled proteins from cells of interest), and transcriptomics assays will be correlated with clinical outcomes and placental histology findings. The hypothesis to be tested is that markers of placental dysfunction early in pregnancy will identify nulliparous women at risk of preterm birth. PUBLIC HEALTH RELEVANCE: Preterm birth affects 12 percent of all pregnancies in the U.S., and complications from preterm delivery are the second leading cause of neonatal mortality. Nulliparous women are an under-studied population, particularly concerning their risk of preterm birth. The proposed network to study preterm birth in nulliparous women has the opportunity to identify risk factors for preterm birth among these women and develop novel therapeutic strategies to prevent preterm deliveries.