Race/Ethnicity/Immunity/Progesterone and Preterm Birth

种族/民族/免疫/黄体酮和早产

• 批准号: 7433334
• 负责人: CARL P WEINER
• 金额: $ 58.19万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7433334
• 关键词: Race; Ethnicity; Immunity; Progesterone; Preterm

Preterm birth (PTB) remains a major public health problem, complicating >10% of all deliveries, and its associated perinatal morbidity and mortality represents 30% of the total. The greatest single risk factor for PTB is a prior PTB. Early and accurate identification of at risk patients may permit targeted interventions. Despite great effort, the US PTB rate has actually increased over the past 30y. This failure reflects a poor understanding of the basic mechanisms initiating PTB coupled to a long held assumption that preterm labor (PL) is simply term labor ill timed. Ascending infection from the lower genital is a well-recognized as a mechanism of upper tract inflammation, fetal inflammatory response syndrome, decidual hemorrhage, chorioamnionitis or combinations thereof. Yet, antibiotic therapy has failed to reduce the PTB rate. It is likely other therapeutic strategies are necessary once the innate immunity of the lower genital tract is overwhelmed and the inflammatory cascade established in the upper genital tract or fetal compartment. We hypothesize that PTB reflects an alteration of oxygen independent (defensins and calgranulins) and oxygen dependent (oxygen free radicals) defense mechanisms of the lower and upper genital tract, and that the sequestration of certain polymorphisms in genes regulating the inflammatory cascade among some ethnic groups accounts in part for their risk of recurrent PTB (Specific Aim 1a). We hypothesize women destined for PTB express cervicovaginal biomarkers illustrative of altered innate immunity weeks or months before onset of PTB symptoms (cervical ripening, preterm labor contractions or pPROM) that can be reliably identified using proteomic tools (Specific Aim 1b). We hypothesize that the progesterone compounds reported to decrease recurrent PTB affect maternal lower and upper genital tract defense mechanisms as well as the fetal inflammatory response axis (Specific Aim 2). This proposal brings together an experienced multidisciplinary team who will test elements of these hypotheses in experiments performed over a 5y period.

早产（PTB）仍然是一个主要的公共卫生问题，占所有分娩的10％及其复杂性 相关的围产期发病率和死亡率占总数的30％。最大的单一风险因素 PTB是先前的PTB。对AT风险患者的早期和准确识别可能允许有针对性的干预措施。 尽管付出了巨大的努力，但在过去30年中，美国PTB的利率实际上已经上升了。这种失败反映了穷人 理解启动PTB的基本机制，并长期以来的假设是早产 （PL）只是劳动生病的时间。从下生殖器上升感染被广泛认可为 上流炎症，胎儿炎症反应综合征，decidual出血的机制， 绒毛膜炎或其组合。然而，抗生素疗法未能降低PTB率。很可能 一旦下生殖道的先天免疫力是 不知所措和在上生殖道或胎儿室中建立的炎症级联。我们 假设PTB反映了氧无关（防御素和加仑蛋白）和氧气的改变 依赖性（氧自由基）上下生殖道的防御机制，并且 在某些种族之间调节炎症级联的基因中某些多态性的隔离 小组的部分原因是其复发性PTB的风险（特定目标1A）。我们假设妇女注定 对于PTB Express宫颈阴道生物标志物，说明了先天免疫改变了几周或几个月之前 可以可靠 使用蛋白质组学工具（特定目标1B）识别。我们假设孕酮化合物 据报道会降低复发性PTB影响母体下生殖道的防御机制 以及胎儿炎症反应轴（特定目标2）。该提议汇集了一个经验丰富的 多学科团队将在5年代内测试实验中这些假设的要素。