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

描述(由申请者提供)：宾夕法尼亚大学卫生系统的产科和妇科反映了在临床和翻译研究方面卓越的悠久传统。母胎医学司的调查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中。在这份申请中，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的拟议患者招募地点。这项申请的具体目标是：1)就网络研究的设计提供咨询，其中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)将受试者纳入网络研究并为网络研究提供高质量的数据；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；以及4)参与网络研究的分析和出版。HUP和PAH的总运送量每年超过9000次。这两家医院的MFM医生共同承担临床责任，并在各种临床研究方面有良好的合作记录。重要的是，这一应用的首席研究员是基因组学和蛋白质组学网络早产研究分析核心的首席研究员，并将为拟议的早产网络带来研究设计、样本收集和分析技术(包括高通量研究)方面的重要专业知识。研究人员提出了一项前瞻性队列研究，在该研究中，产前超声检查结果(宫颈长度、子宫动脉多普勒血流)、蛋白质生物标记物(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)以及转录物分析将与临床结果和胎盘组织学结果相关。需要检验的假设是，怀孕早期胎盘功能障碍的标记物将识别有早产风险的未分娩妇女。 与公共卫生相关：在美国，早产影响了12%的怀孕，早产并发症是新生儿死亡的第二大原因。未分娩的妇女是一个研究不足的人群，特别是关于她们早产的风险。拟议的研究未分娩妇女早产的网络有机会确定这些妇女早产的风险因素，并开发预防早产的新的治疗策略。

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.