BV-associated bacteria and adverse pregnancy outcomes among urban women

描述（由申请人提供）：自发性早产（SPTB）影响了城市妇女所有分娩的12%以上，并导致了所有婴儿死亡的三分之一以上。许多不良妊娠结局与BV（包括SPTB）有前瞻性关联。尽管BV和SPTB之间的流行病学联系一直很强，但许多BV阳性孕妇分娩健康的足月婴儿，目前BV的治疗方案基本无效。BV阳性妇女中存在微生物变异，这种变异性可能解释甲硝唑治疗BV和/或降低SPTB风险的有限有效性。这一修订后的竞争性延续申请的目的是：1）评价在妊娠前三个月测量的阴道加德纳氏菌、柯氏动弯孢菌、阴道变形菌、阴道细毛菌和命名为细菌性阴道病相关细菌（BVAB）1、2或3的梭菌目细菌是否是SPTB的重要的独立预测因子，和2）评价阴道加德纳氏菌是否持续高水平，在妊娠期间的两个时间点测量Curtisi移动弯钩菌、阴道变形菌、Leptotrichia pastonii和细菌性阴道病相关细菌（BVAB）1、2或3，是SPTB的重要独立预测因子。将招募怀孕12周或更短时间在坦普尔大学参加首次产前护理的妇女。基线数据收集将标准化，包括结构化的面对面访谈、用于三种炎性基因基因分型的口腔拭子和用于基于革兰氏染色检测BV存在和程度的阴道拭子。此外，将使用靶向来自目标BV相关细菌的16 S rRNA基因的PCR测定法测量选定阴道细菌的浓度。在妊娠18 -20周之间重复采集阴道拭子，以检查这些细菌的变化以及持续高水平BV相关细菌和SPTB风险的作用。在这项病例队列研究中，我们将在三年内招募2200名孕妇并对其进行分类，并随机抽取20%的潜在人群以产生子队列。我们将确定所有发生在子队列内外的SPTB病例，并将结果与其余子队列进行比较。鉴于SPTB导致的婴儿高发病率和死亡率对公共卫生的影响，这些结果可能会根据妊娠早期BV特征识别出一组SPTB高风险女性。这些结果还将研究城市BV阳性妇女SPTB风险增加的主要生物机制和辅助因素，以及目前BV治疗方案的无效性。公共卫生相关性：自发性早产（SPTB）影响所有出生的12%以上，并导致所有婴儿死亡的三分之一以上。尽管BV和SPTB之间的流行病学联系一直很强，许多BV阳性孕妇分娩健康的足月婴儿。这项研究的结果将增加关于与SPTB最相关的特定BV相关细菌的有价值的信息，并可能解释目前BV治疗在降低SPTB风险方面的有限有效性。

DESCRIPTION (provided by applicant): Spontaneous preterm birth (SPTB) affects more that 12 percent of all births among urban women and contributes to more than one-third of all infant deaths. Numerous adverse pregnancy outcomes have been prospectively linked to BV including SPTB. Despite the consistently strong epidemiologic link between BV and SPTB, many BV positive pregnant women deliver healthy, term infants and the current treatment options for BV are largely ineffective. Microbiologic variations exist among BV positive women and this variability may explain the limited effectiveness of metronidazole in curing BV and/or reducing SPTB risk. The aims of this amended, competing continuation application are: 1) to evaluate whether Gardnerella vaginalis, Mobiluncus curtisii, Atopobium vaginae, Leptotrichia amnionii, and the Clostridiales bacteria designated Bacterial Vaginosis-Associated Bacterium (BVAB) 1,2 or 3 measured in the first trimester of pregnancy are important, independent predictors of SPTB, and 2) to evaluate whether consistently high levels of Gardnerella vaginalis, Mobiluncus curtisii, Atopobium vaginae, Leptotrichia amnionii, and Bacterial Vaginosis-Associated Bacteria (BVAB) 1,2 or 3, measured at two points during pregnancy, are an important, independent predictor of SPTB. Women attending their first prenatal care visit at Temple University with a pregnancy of 12 weeks gestation or less will be recruited. Baseline data collection will be standardized and include a structured in- person interview, buccal swab for genotyping of three inflammatory genes, and vaginal swabs to detect the presence and degree of BV based on Gram stain. In addition, the concentrations of selected vaginal bacteria will be measured using PCR assays targeting 16S rRNA genes from the BV-associated bacteria of interest. Repeat vaginal swabs will be collected between18-20 weeks gestation to examine the change in these bacteria and the role of consistently high levels of BV-associated bacteria and SPTB risk. In this case-cohort study, we will enroll and classify 2200 pregnant women over a three year period and randomly sample 20 percent of the underlying population to generate the subcohort. We will identify all SPTB cases occurring within and outside the subcohort and compare the results to the remaining subcohort. Given the public health impact of high rates of infant morbidity and mortality due to SPTB, these results may identify a group of women at high risk of SPTB based on early pregnancy BV profile characteristics. These results will also examine the biologic mechanisms and co-factors most responsible for the increased risk of SPTB among urban, BV positive women and the ineffectiveness of current BV treatment options. PUBLIC HEALTH RELEVANCE: Spontaneous preterm birth (SPTB) affects more that 12 percent of all births and contributes to more than one-third of all infant deaths. Despite the consistently strong epidemiologic link between BV and SPTB, many BV positive pregnant women deliver healthy, term infants. The results from this study will add valuable information regarding the specific BV-associated bacteria most related to SPTB and may explain the current limited effectiveness of BV treatment in reducing the risk of SPTB.