Triggers of Abruptio Placentae - A Case Crossover Study of an Ischemic Placental

胎盘早剥的触发因素——缺血性胎盘的病例交叉研究

基本信息

批准号：
8141387
负责人：
Cande V. Ananth
金额：
$ 55.08万
依托单位：
SWEDISH MEDICAL CENTER, FIRST HILL
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-10 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8141387
关键词：
Abdomen Abruptio Placentae Acute Address Alcohol consumption Blood Platelets Cells Chronic Clinical Coagulation Process Collection Complication Cross-Over Studies Crossover Design DNA Data Databases Development Diagnosis Discipline of obstetrics Disease Enrollment Epidemiologic Studies Epidemiology Etiology Evaluation Exertion Exposure to Fetal Death Fetal Growth Retardation Fibrinolysis Functional disorder Genes Genetic Goals Haplotypes Hemorrhagic Shock Hour Hypoxia Implant Infant Infarction Infection Inflammation Inherited Intervention Interview Ischemia Kidney Failure Life Medical Records Methods Mothers Muscle Cramp Newborn Infant Pathogenesis Pathway interactions Perinatal Disorder Persons Peru Physical activity Placenta Placental Infarction Pre-Eclampsia Pregnancy Pregnancy Outcome Premature Birth Prevention Prevention strategy Preventive Intervention Primary Prevention Public Health Relative Risks Renin-Angiotensin System Research Research Design Research Personnel Risk Risk Factors Saliva Sampling Scanning Screening procedure Secondary to Sex Behavior Single Nucleotide Polymorphism Specific qualifier value Specimen Staging Sympathetic Nervous System Trauma Uterine hemorrhage Vagina Variant Vehicle crash Woman advanced maternal age adverse outcome angiogenesis base binge drinking case control clinical care density design falls fetal folic acid metabolism genetic variant hazard insight intimate partner violence maternal cigarette smoking novel strategies premature public health relevance

项目摘要

DESCRIPTION (provided by applicant): Abruptio placentae (AP), the premature separation of the placenta, is a life threatening obstetric condition that complicates roughly 1-2 percent of all pregnancies. Pathophysiologic mechanisms involved in AP (and related perinatal disorders - preterm birth, preeclampsia, and intrauterine growth restriction) include uteroplacental ischemia, underperfusion, chronic hypoxia, and infarctions. On this basis, investigators have begun to conceptualize abruption as an "ischemic placental disorder" characterized by acute and chronic pathophysiological features. Furthermore, evidence suggests that transient activation of the sympathetic nervous system might trigger AP. The etiology of AP remains unknown, though results from previous studies suggest some risk factors and emerging evidence suggest a significant genetic component in the pathogenesis of AP. At present, neither an accurate prediction nor prevention of AP is possible. We seek to increase our understanding of the epidemiology and pathophysiology of AP by conducting a large multi-center epidemiologic study of AP in Lima, Peru. We will use the self-matched case-crossover design to evaluate the acute effects of: 1) maternal smoking and alcohol consumption; 2) physical exertion; 3) sexual activity; 4) abdominal trauma secondary to falls or motor vehicle crashes; and 5) exposure to intimate partner violence as potential "triggers" of AP. The risk of AP will be assessed during pre-specified hazard periods. We will also use the case-control replicative (two stage) study design to study genetic variants that influence the pathogenesis of AP in well characterized 900 mother-infant abruption case pairs and 900 mother-infant control pairs. We plan to focus on specific gene pathways, including coagulation, fibrinolysis, platelet function, infection and inflammation, angiogenesis, folate metabolism, and the renin-angiotensin systems that have previously been associated with AP. In Stage 1, we will use a high-density single nucleotide polymorphism (SNP) "1536-chip" on the 1st half of samples to scan maternal and infant SNPs and SNP haplotypes for association with AP. In Stage 2, we will select ~200 of the most pertinent candidate SNPs for replication in the 2nd half of samples. We hypothesize that genes associated with substantial relative risk of AP in Stage 1 will replicate in the independent sample set used in Stage 2. Results from these proposed studies will reveal new insights into the pathophysiology of AP by formally exploring possible interactions between prolonged and habitual exposures (e.g., habitual alcohol consumption and physical activity) and triggering effects of factors such as binge drinking or extreme physical exertion. Results will also yield new insights into the inherited genetic bases of AP. Collectively, these new insights may facilitate the development of new approaches for the primary prevention of AP (at the public health level) and may also facilitate the development of new therapies and methods for diagnosis. PUBLIC HEALTH RELEVANCE: Abruptio placentae (AP), is of global public health importance in large part because of its association with adverse outcomes in newborns and mothers including preterm delivery, fetal death, maternal hemorrhagic shock, and renal failure. We will use the self-matched case-crossover design to study the transient effects of putative "triggers" of AP; and we will use the case-control design to study genetic variants that influence the pathogenesis of AP in 900 mother-infant abruption case pairs and 900 mother-infant control pairs. Results from our research have a very high potential for yielding etiologic and clinical information that may prove to be effective in the identification of women at greatest need of specific preventive interventions and specialized clinical care.

描述（由申请人提供）：胎盘的过早分离胎盘（AP）是一种威胁生命的产科条件，使大约1-2％的所有怀孕都复杂化。与AP有关的病理生理机制（和相关的围产期疾病 - 早产，子痫前期和宫内生长限制）包括子宫牙科缺血，灌注不足，慢性缺氧和梗塞。在此基础上，研究人员已开始将破裂概念化为以急性和慢性病理生理特征为特征的“缺血性胎盘疾病”。此外，有证据表明交感神经系统的短暂激活可能触发AP。 AP的病因仍然未知，尽管先前研究的结果表明一些危险因素和新兴证据表明AP发病机理中具有重要的遗传成分。目前，准确的预测和对AP的预防都不是无法进行的。我们试图通过对秘鲁利马的AP进行大型多中心流行病学研究来提高AP的流行病学和病理生理学的理解。我们将使用自匹配的案例交叉设计来评估：1）孕产妇吸烟和饮酒； 2）身体劳累； 3）性活动； 4）继发于跌倒或机动车坠毁的腹部创伤； 5）暴露于亲密伴侣暴力作为AP的潜在“触发”。将在预先指定的危险期间评估AP的风险。我们还将使用病例对照复制（两个阶段）研究设计来研究影响AP发病机理的遗传变异，以良好的表征900个母含量的突然案例对和900个母亲控制对。我们计划专注于特定的基因途径，包括凝血，纤维蛋白溶解，血小板功能，感染和炎症，血管生成，叶酸代谢以及以前与AP相关的肾素 - 血管紧张素系统。在第1阶段中，我们将使用高密度的单核苷酸多态性（SNP）在第一部分样品上“ 1536-Chip”来扫描母体和婴儿SNP以及SNP单倍型与AP相关。在第2阶段，我们将在第二部分中选择约200个最相关的候选SNP进行复制。我们假设阶段1中与AP的实质相对风险相关的基因将在第2阶段使用的独立样本集中复制。这些拟议的研究的结果将通过正式探索延长和习惯性暴露之间的可能相互作用来揭示对AP的病理生理学的新见解。（例如，习惯性饮酒和体育锻炼）以及诸如暴饮暴食或极端身体劳累等因素的影响。结果还将对AP的遗传遗传基础产生新的见解。总的来说，这些新见解可能有助于开发主要预防AP的新方法（在公共卫生水平上），也可能有助于开发新的疗法和诊断方法。公共卫生相关性：胎盘（AP）在很大程度上具有全球公共卫生的重要性，因为它与新生儿和母亲的不良后果相关，包括早产，胎儿死亡，孕产妇出血性休克和肾衰竭。我们将使用自匹配的案例交叉设计来研究AP的假定“触发器”的瞬态效应；我们将使用病例对照设计来研究影响900张母亲突然案例对和900个母子控制对的AP发病机理的遗传变异。我们研究的结果具有产生病因和临床信息的很高潜力，这些信息可能被证明可以有效地鉴定出最需要特定的预防性干预措施和专门的临床护理的妇女。