Maternal markers and prediction of preeclampsia

先兆子痫的母亲标志物和预测

• 批准号: 7840419
• 负责人: Lorraine Dugoff
• 金额: $ 7.58万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-12 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7840419
• 关键词: Antiplatelet Drugs; Ascorbic Acid; Biological Assay; Biological Markers; Blood flow; Blood specimen; Calcium; Caring; Cessation of life; Characteristics; Chronic; Clinical Data; Clinical Research; Collaborations; Colorado; Data; Databases; Development; Discipline of obstetrics; Disease; Early Diagnosis; Early identification; Early intervention trials; Edema; Educational workshop; Fetal Growth Retardation; First Pregnancy Trimester; Future; General Population; Goals; Gynecology; Hemolysis; Hour; Hypertension; Inhibin A; Institution; Intervention; Kidney; Lead; Maryland; Measures; Modeling; Monitor; Morbidity - disease rate; Mothers; National Institute of Child Health and Human Development; Nested Case-Control Study; Organ failure; Outcome; Patients; Perinatal; Pharmaceutical Preparations; Placenta; Population; Pre-Eclampsia; Pregnancy; Pregnant Women; Premature Birth; Prevalence; Proteinuria; Randomized; Recruitment Activity; Research; Research Priority; Risk; Risk Factors; Sampling; Science; Screening procedure; Seizures; Serum; Serum Markers; Signs and Symptoms; Site; Sorting - Cell Movement; Stroke; Suggestion; Syndrome; Techniques; Therapeutic Agents; Thrombocytopenia; Time; United States National Institutes of Health; Universities; Woman; Women' s Health; activin A; cohort; design; disorder risk; fetal; high risk; improved; maternal serum; maternal serum markers; mortality; novel; placental protein 13; premature; prevent; prophylactic; public health relevance; repository; reproductive; tool; treatment effect

DESCRIPTION (provided by applicant): Preeclampsia is the leading cause of maternal and fetal morbidity and mortality in the world. This pregnancy- specific syndrome generally develops after the twentieth week of gestation, and can lead to major maternal morbidity or death. At the same time, reduced placental blood flow can lead to fetal growth restriction, premature delivery for maternal or fetal indications, and fetal morbidity and mortality. At the present time there are no proven interventions to prevent preeclampsia. The overall goal of this research will be to identify women in the first trimester who are at increased risk of developing preeclampsia later in pregnancy. The specific aims of this project are: (1) To compare first trimester levels of inhibin A, PP13, activin A and ADAM12 from women who subsequently developed preeclampsia to levels seen in control women, and (2) To develop a multivariate prediction model for preeclampsia using these first trimester maternal serum markers in combination with a panel of maternal characteristics as recorded in our database. The nested case control study will select preeclamptic and control (women who did not develop preeclampsia) patients from existing data contained in the University of Colorado Department of OB-GYN Database and a database from the Department of Obstetrics, Gynecology and Reproductive Sciences at the University of Maryland. By merging data from these two centers we will have access to comprehensive clinical data including maternal characteristics and outcomes from 4,000 pregnancies (approximately 2,000 women from each site as of December, 2008). Blood samples drawn from these patients between 9 and 14 weeks gestation have been stored in sample repositories at both institutions, and will be available for assay. The study will make use of a well established research team, preexisting and well-characterized data, access to PP13 and ADAM12 assays, and collaboration with accomplished experts in devising prediction modeling in adverse perinatal outcome. The aims of the proposed study have been identified as a 2008 NIH Research Priority for Women's Health in a document issued by the Research Subcommittee of the NIH Coordinating Committee on Research on Women's Health in November, 2007. This document specifically encouraged research "in early detection and treatment, including the development of novel tools to identify and validate biomarkers in relation to disease risk". The study is significant because preeclampsia is a leading cause of fetal and maternal death worldwide, and first trimester prediction of preeclampsia will have the effect of promoting and accelerating the search for prophylactic and therapeutic agents for preeclampsia. In addition identification of early markers of preeclampsia would lead to closer scrutiny of at risk pregnancies and may provide information regarding the mechanism of the disease. PUBLIC HEALTH RELEVANCE: A critical goal in improving the care of women with preeclampsia is to identify women at risk even before the disease is manifest. The ability to identify these women early in their pregnancy would allow closer monitoring in the short term, and in the longer term could lead to future trials of promising drugs or techniques that might forestall or even prevent the disease. Accomplishing either of these objectives would lead to reduced morbidity and mortality of both mothers and babies.

描述（由申请人提供）：先兆子痫是世界上孕产妇和胎儿发病率和死亡率的主要原因。这种妊娠特异性综合征通常在妊娠20周后发生，并可导致重大孕产妇发病或死亡。同时，胎盘血流量减少可导致胎儿生长受限、母体或胎儿适应症早产以及胎儿发病和死亡。目前还没有经过证实的干预措施来预防先兆子痫。这项研究的总体目标将是确定在怀孕的前三个月谁是在发展先兆子痫的风险增加的妇女在怀孕后期。该项目的具体目的是：（1）比较随后发展为先兆子痫的妇女与对照妇女中观察到的水平的前三个月的Bisobin A，PP 13，激活素A和ADAM 12水平，以及（2）使用这些前三个月的母体血清标记物结合我们数据库中记录的一组母体特征来开发先兆子痫的多变量预测模型。巢式病例对照研究将从科罗拉多大学妇产科数据库和马里兰州大学妇产科和生殖科学系数据库中的现有数据中选择先兆子痫和对照（未发生先兆子痫的女性）患者。通过合并这两个中心的数据，我们将获得全面的临床数据，包括4,000例妊娠的孕产妇特征和结局（截至2008年12月，每个中心约有2,000名妇女）。从这些妊娠9 - 14周的患者中抽取的血液样本已储存在两家机构的样本库中，并可用于分析。该研究将利用一个完善的研究团队，预先存在的和充分表征的数据，获得PP 13和ADAM 12检测，并与有成就的专家合作，设计围产期不良结局的预测模型。拟议的研究的目的已被确定为2008年美国国立卫生研究院妇女健康研究的优先事项，在一份文件中发表的美国国立卫生研究院妇女健康研究协调委员会的研究小组委员会在2007年11月。该文件特别鼓励“早期发现和治疗方面的研究，包括开发新工具来识别和验证与疾病风险相关的生物标志物”。该研究意义重大，因为先兆子痫是全球胎儿和孕产妇死亡的主要原因，先兆子痫的早期预测将具有促进和加速寻找先兆子痫预防和治疗药物的作用。此外，先兆子痫的早期标志物的鉴定将导致对高危妊娠的更仔细的审查，并可能提供关于疾病机制的信息。 公共卫生关系：改善先兆子痫妇女护理的一个关键目标是在疾病明显之前就确定处于危险中的妇女。在怀孕早期识别这些妇女的能力将允许在短期内进行更密切的监测，从长远来看，可能会导致未来有希望的药物或技术的试验，这些药物或技术可能会阻止甚至预防这种疾病。实现这两个目标中的任何一个都将导致降低母亲和婴儿的发病率和死亡率。