Mechanisms for Racial Disparity in Preterm Birth

描述(由申请人提供)：我们建议以人口为基础的五年 评估早产相对贡献的前瞻性队列研究 出生10例生殖道感染、母体应激与遗传 非裔美国人和白人对增强免疫反应的易感性 华盛顿州金县的女性居民。潜在的主题将是 通过出生证明数据确定的，并采取适当措施 保护机密性。我们将招收100名非裔美国人和100名白人 怀孕20-34周有过早产经历的妇女 100名非裔美国人和100名白人女性的对照组 36周时出生。初步评估将至少进行6个月 在指数交付后，将包括阴道菌群评估和 子宫内膜炎，通过定性和定量测量的母体压力， 牙周炎和细胞因子产生的遗传变异性。我们会提供 参与者治疗或转诊任何可改变的早产危险因素 在初始评估中确定的出生。然后我们将跟随 受试者具有前瞻性，预计30%-40%的受试者将有 随访期内继续妊娠。再次怀孕的女性将 提供阴道菌群、宫颈长度和母亲压力的评估 对可改变的危险因素提供治疗或转诊。的结果 第二次怀孕将被确定。这项研究设计将使我们能够 考察以下具体目标：1.研究增加抗原性的作用 下生殖道感染的刺激作为决定因素 非裔美国人子宫内膜炎、绒毛膜羊膜炎与早产 白人女性。2.考察母体压力与炎症的相关性 性唤醒，按种族和既往孕产史分层。3.评估母亲 和胎儿基因对促炎反应的贡献及其相互关系 这些与早产和新生儿结局有关。总而言之，这些 相互关联的目标将解决非洲国家通过哪些机制 美国女性患癌症的可能性仍然是白人女性的至少两倍 过早地交付。我们还计划探索基因之间的协同作用 易感性、母亲压力、炎症性唤醒、下生殖道 感染和早产。我们假设有不止一个的女人 易感因素显著增加早产的风险，以及 非裔美国女性比白人女性更有可能有多个 诱因。我们希望这些研究最终可能导致 制定更有效的策略来预防早产和 缩小早产、低出生体重和婴儿死亡率的差距 在非裔美国人和白人女性之间。

DESCRIPTION (provided by applicant): We propose a five year population-based prospective cohort study to evaluate the relative contributions to pre term birth of 10 genital tract infection, maternal stress and a genetic predisposition to an enhanced immune response among African American and white women resident in King County, Washington. Potential subjects will be identified through birth certificate data, with appropriate measures to protect confidentiality. We will enroll 100 African American and 100 white women with a prior early preterm birth at 20-34 weeks gestation and a comparison group of 100 African American and 100 white women with prior term birth at >36 weeks. The initial assessment will be performed at least 6 months after the index delivery and will include evaluation of vaginal flora and endometritis, maternal stress by qualitative and quantitative measures, periodontitis, and genetic variability in cytokine production. We will offer participants treatment or referral for any modifiable risk factors for preterm birth that are identified in the initial evaluation. We will then follow subjects prospectively and anticipate that 30-40% of the cohort will have a subsequent pregnancy during follow-up. Women with a subsequent pregnancy will be offered evaluation of vaginal flora, cervical length, and maternal stress with treatment or referral offered for modifiable risk factors. Outcomes for second pregnancies will be ascertained. This study design will allow us to examine the following specific aims: 1. Study the role of increased antigenic stimulation from lower genital tract infection as a determinant of endometritis, chorioamnionitis and preterm birth among African American and white women. 2. Examine the correlation of maternal stress with inflammatory arousal, stratified by race and prior pregnancy history. 3. Assess maternal and fetal genetic contributions to the pro-inflammatory response and correlate these with preterm birth and neonatal outcome. In combination, these inter-related aims will address the most plausible mechanisms by which African American women continue to be at least twice as likely as white women to deliver prematurely. We also plan to explore the synergy between genetic predisposition, maternal stress, inflammatory arousal, lower genital tract infection, and preterm birth. We hypothesize that women with more than one predisposing factor are at a markedly increased risk for preterm birth, and that African American women are more likely than white women to have multiple predisposing factors. We hope that these studies may eventually lead to the development of more effective strategies to prevent preterm birth and to reduce the disparity in preterm birth, low birthweight and infant mortality between African American and white women.