BV-associated bacteria and adverse pregnancy outcomes among urban women

描述（由申请人提供）：自发性早产（SPTB）占城市妇女分娩总数的12%以上，占婴儿死亡总数的三分之一以上。包括SPTB在内的许多不良妊娠结局可能与BV有关。尽管BV和SPTB之间的流行病学联系一直很强，但许多BV阳性的孕妇分娩出健康的足月婴儿，目前BV的治疗方案在很大程度上是无效的。细菌性阴道炎阳性妇女中存在微生物差异，这种差异可能解释了甲硝唑在治疗细菌性阴道炎和/或降低SPTB风险方面的有限效果。这项经修订的竞争性延续申请的目的是：1)评估妊娠早期检测的阴道加德纳菌、阴道Mobiluncus curtisii、阴道托单胞菌、羊水细毛菌和梭状芽胞菌指定的细菌性阴道病相关细菌（BVAB） 1、2或3是否重要，是否是SPTB的独立预测因子；2)评估持续高水平的阴道加德纳菌、阴道Mobiluncus curtisii、阴道托单胞菌、羊水细毛菌和细菌性阴道病相关细菌（BVAB） 1,2或3，在怀孕期间的两个点测量，是一个重要的，独立的预测SPTB。在天普大学参加第一次产前护理的怀孕12周或更短时间的妇女将被招募。基线数据收集将标准化，包括结构化的面对面访谈，口腔拭子对三种炎症基因进行基因分型，阴道拭子根据革兰氏染色检测细菌性阴道炎的存在和程度。此外，选择阴道细菌的浓度将通过PCR检测bv相关细菌的16S rRNA基因来测定。将在妊娠18-20周期间反复收集阴道拭子，以检查这些细菌的变化以及持续高水平的细菌性疱疹相关细菌和SPTB风险的作用。在这个病例队列研究中，我们将在三年的时间内招募2200名孕妇并对其进行分类，并随机抽取20%的潜在人群来生成亚队列。我们将确定发生在亚队列内外的所有SPTB病例，并将结果与其余亚队列进行比较。鉴于SPTB引起的婴儿高发病率和死亡率对公共卫生的影响，这些结果可能根据妊娠早期BV谱特征确定一组SPTB高危妇女。这些结果还将检验导致城市细菌性阴道炎阳性妇女患SPTB风险增加的生物学机制和辅助因素，以及目前细菌性阴道炎治疗方案的有效性。公共卫生相关性：自发性早产（SPTB）影响了所有出生人数的12%以上，造成了所有婴儿死亡人数的三分之一以上。尽管细菌性阴道炎和SPTB之间一直存在很强的流行病学联系，但许多细菌性阴道炎阳性的孕妇分娩出健康的足月婴儿。这项研究的结果将为与SPTB最相关的特定细菌性疱疹病毒相关细菌提供有价值的信息，并可能解释目前细菌性疱疹病毒治疗在降低SPTB风险方面的有限效果。

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.