BV-associated bacteria and adverse pregnancy outcomes among urban women

描述(申请人提供)：自发性早产(SPTB)影响城市妇女所有分娩的12%以上，并导致超过三分之一的婴儿死亡。许多不良妊娠结局被预期与包括SPTB在内的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阳性的孕妇生产的是健康的足月婴儿，目前的BV治疗方案大多无效。在BV阳性妇女中存在微生物学差异，这种差异可能解释了甲硝唑在治疗BV和/或降低SPTB风险方面的有限有效性。这项修订后的竞争性继续应用的目的是：1)评估孕期两个时间点测量的加德纳氏菌、柯蒂斯移动杆菌、阴道阿托波氏菌、羊毛细毛杆菌和指定为细菌性阴道病相关细菌(BVAB)1、2或3的梭状杆菌是否是SPTB的重要独立预测因子；2)评估持续高水平的阴道加德纳菌、Curtisii移动杆菌、阴道阿托伯菌、羊毛细毛杆菌和细菌性阴道病相关细菌(BVAB)1、2或3是否是SPTB的重要独立预测因子。在坦普尔大学参加第一次产前检查的怀孕12周或以下的妇女将被招募。基线数据收集将标准化，包括结构化的面谈，用于三种炎症基因基因分型的口腔拭子，以及基于革兰氏染色检测BV存在和程度的阴道拭子。此外，将使用针对感兴趣的BV相关细菌的16S rRNA基因的聚合酶链式反应分析来测量选定的阴道细菌的浓度。重复的阴道拭子将在妊娠18-20周期间收集，以检查这些细菌的变化以及持续高水平的BV相关细菌和SPTB风险的作用。在这项病例队列研究中，我们将在三年内对2200名孕妇进行登记和分类，并从20%的潜在人群中随机抽样，以产生亚队列。我们将确定发生在亚群组内外的所有SPTB病例，并将结果与其余亚群组进行比较。鉴于SPTB导致的高婴儿发病率和死亡率对公众健康的影响，这些结果可能会根据早孕BV特征确定一组高风险的SPTB妇女。这些结果还将检验导致城市BV阳性妇女中SPTB风险增加的生物机制和辅助因素，以及当前BV治疗方案的无效。公共卫生相关性：自发性早产(SPTB)影响了超过12%的新生儿，并导致了超过三分之一的婴儿死亡。尽管BV和SPTB之间的流行病学联系一直很强，但许多BV阳性的孕妇生产的是健康的足月婴儿。这项研究的结果将增加与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.