QUANTITATIVE MICROBIOLOGIC MODEL FOR PRETERM DELIVERY

描述(申请人提供)：早产(PTD)是领先的 美国婴儿发病和死亡的原因，预防措施是 围产期保健的主要目标。最近的证据表明， 怀孕期间阴道微生物群的改变与 PTD的发生。然而，特定微生物在PTD中的作用 还没有被很好地理解。这个实验室最近的研究是针对 确定与PTD相关的特定微生物风险因素。我们有 在此基础上，建立了PTD的预测统计模型 微生物风险因素。我们的研究确定了两个关键人群 与PTD的发生有关。事实证明， 细菌磷脂酶的水平，磷脂酶A2，浓度增加在20 怀孕不到37周的妇女怀孕30周。 PLA2的这种增加与普雷沃特氏菌的存在有关。作为以下内容的一部分 阴道微生物区系。还注意到，两者的存在 产过氧化氢(H_2O_2)乳杆菌和非H_2O_2产生菌 乳杆菌同时作为阴道微生物区系的一部分是一个危险因素 对于PTD，与任何一种菌株本身的存在分开。 这一观察表明，菌株的组合可能具有有害的 对妊娠结局的影响。拟议项目的目标是 前瞻性地收集定量和定性的微生物学数据 患有PTD的高危女性和无PTD可识别风险的女性， 确定统计模型是否能够基于以下项预测PTD 微生物学数据，为后续研究做准备，在该研究中， 被该模型识别为PTD风险的患者将得到治疗。此外， 将对细菌引起PTD的实际机制(S)进行评估，以便 确定任何干预性研究的微生物学靶点。具体目标 这项建议的目的是：1)改进从 对今年头三年收集的数据进行初步分析 研究并验证了该模型在未来一段时间预测PID的有效性 临床试验，2)提高对特异性药物作用的认识 PTD中的细菌种类，特别是普氏杆菌，3)采用分子分型 确定特定的乳酸菌菌株是否更常见的方法 妊娠37周以下分娩的妇女比怀孕37周以下的妇女 怀孕37周以上，以及这些病毒是否在怀孕期间获得；以及 4)确定乳酸菌菌株之间的相互作用 使用培养的阴道上皮细胞对孕妇有害 在体外暴露于体内发现的乳酸菌组合。

DESCRIPTION (provided by applicant): Preterm delivery (PTD) is the leading cause of infant morbidity and mortality in the United States, and prevention is a primary goal for perinatal health care. Recent evidence indicates that there is a strong association between an altered vaginal microflora during pregnancy and the occurrence of PTD. However, the role of specific microorganisms in PTD is not well understood. Recent studies in this laboratory have been directed at identifying specific microbial risk factors associated with PTD. We have established a predictive statistical model for PTD, based on these microbiologic risk factors. Our studies have identified two key populations that are associated with the occurrence of PTD. It has been shown that the levels of a bacterial phospholipase, PLA2, increase in concentration between 20 and 30 weeks of gestation in women who deliver at less than 37 weeks gestation. This increase in PLA2 correlates with the presence of Prevotella sp. as part of the vaginal microflora. It has also been noted that the presence of both hydrogen peroxide (H2O2) producing lactobacilli and non-H2O2 producing lactobacilli simultaneously as part of the vaginal microflora is a risk factor for PTD, separate from the presence of either strain by itself. This observation suggests that combinations of strains may have a detrimental effect on pregnancy outcome. The goal of the proposed project is to prospectively collect quantitative and qualitative microbiologic data from women at high risk for PTD and those with no identifiable risk for PTD, to determine whether the statistical model is capable of predicting PTD based on microbiologic data, in preparation for a subsequent study in which women identified as at risk for PTD by this model will be treated. In addition, the actual mechanism(s) by which bacteria cause PTD will be evaluated in order to identify microbiologic targets for any interventional study. The specific aims for this proposal are to 1) refine the predictive model derived from the initial analysis of the data collected during the first three years of this study and to validate this model for predicting PID during a prospective clinical trial, 2) to improve out understanding of the role of specific bacterial species in PTD particularly Prevotella sp, 3) to use molecular typing methods to determine whether specific strains of lactobacilli are more common in women delivering at less than 37 weeks gestation than those delivering at 37+ weeks gestation and whether such strains are acquired during pregnancy, and 4) to determine whether interactions between strains of lactobacilli deleterious to pregnant women occur by using cultured vaginal epithelial cells in vitro exposed to combinations of lactobacilli found in vivo.