BV-associated bacteria and adverse pregnancy outcomes among urban women

城市女性 BV 相关细菌与不良妊娠结局

• 批准号: 7464467
• 负责人: Deborah B Nelson
• 金额: $ 44.73万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-06-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7464467
• 关键词: Affect; Anaerobic Bacteria; Bacteria; Bacterial Genes; Bacterial Typing; Bacterial Vaginosis; Biological Assay; Birth; Cessation of life; Characteristics; Chronic; Cohort Analysis; Cohort Studies; Complex; Data Collection; Death Rate; Effectiveness; Enrollment; First Pregnancy Trimester; Gardnerella vaginalis; Genes; Genotype; Gram' s stain; High Risk Woman; Infant; Inflammatory; Interview; Leptothrix; Leptotrichia; Link; Measurement; Measures; Metronidazole; Mobiluncus curtisii; Morbidity - disease rate; Persons; Polymerase Chain Reaction; Population; Pregnancy; Pregnancy Outcome; Pregnant Women; Premature Birth; Prenatal care; Public Health; Rate; Recruitment Activity; Ribosomal RNA; Risk; Role; Sampling; Structure; Swab; Syndrome; Time; Universities; Vagina; Variant; Visit; Week; Woman; Women' s Group; base; birth control; interest; mortality; pathogen; prospective; routine Bacterial stain

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.

描述（由申请人提供）：自然早产 (SPTB) 影响城市妇女所有分娩的 12% 以上，并导致所有婴儿死亡的三分之一以上。包括 SPTB 在内的许多不良妊娠结局已被前瞻性地与 BV 相关。尽管 BV 和 SPTB 之间始终存在很强的流行病学联系，但许多 BV 阳性孕妇生下健康的足月婴儿，而目前 BV 的治疗方案基本上无效。 BV 阳性女性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 风险方面效果有限的原因。这项修订后的竞争性延续申请的目的是：1) 评估在妊娠前三个月测量的阴道加德纳菌、柯蒂斯动杆菌、阴道阿托波菌、羊膜纤毛菌和被称为细菌性阴道病相关细菌 (BVAB) 1,2 或 3 的梭状芽胞杆菌是否是 SPTB 的重要独立预测因子，以及 2) 评估在怀孕期间的两个时间点测量的阴道加德纳菌、柯蒂斯动杆菌、阴道阿托波菌、羊膜纤毛菌和细菌性阴道病相关细菌 (BVAB) 1,2 或 3 的持续高水平是否是 SPTB 的重要、独立预测因子。将招募怀孕 12 周或更短时间到天普大学进行首次产前护理的女性。基线数据收集将被标准化，包括结构化的面对面访谈、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细菌性阴道炎的存在和程度的阴道拭子。此外，将使用针对 BV 相关细菌的 16S rRNA 基因的 PCR 测定来测量选定的阴道细菌的浓度。将在妊娠 18-20 周期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的 BV 相关细菌和 SPTB 风险的作用。在此案例队列研究中，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% 的基础人群来生成子队列。我们将识别该子队列内外发生的所有 SPTB 病例，并将结果与​​其余子队列进行比较。考虑到 SPTB 导致的高婴儿发病率和死亡率对公共健康的影响，这些结果可能会根据妊娠早期 BV 谱特征识别出一组处于 SPTB 高风险的女性。这些结果还将研究导致城市 BV 阳性女性 SPTB 风险增加以及当前 BV 治疗方案无效的生物学机制和辅助因素。公共卫生相关性：自发性早产 (SPTB) 影响超过 12% 的新生儿，并导致超过三分之一的婴儿死亡。尽管 BV 和 SPTB 之间始终存在很强的流行病学联系，但许多 BV 阳性孕妇生下健康的足月婴儿。这项研究的结果将增加有关与 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 风险方面效果有限的原因。