QUANTITATIVE MICROBIOLOGIC MODEL FOR PRETERM DELIVERY

早产的定量微生物模型

• 批准号: 6430137
• 负责人: ANDREW B. ONDERDONK
• 金额: $ 37.86万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-01-01 至 2004-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6430137
• 关键词: Lactobacillus; bacterial disease; cervical /vaginal smear; clinical research; diagnosis design /evaluation; disease /disorder proneness /risk; female; human morbidity; human mortality; human pregnant subject; hydrogen peroxide; infant mortality; mathematical model; microorganism interaction; microorganism population study; model design /development; nucleic acid quantitation /detection; perinatal; phospholipase A2; polymerase chain reaction; pregnancy infection; premature infant human; premature labor; women's health

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.

描述（由申请人提供）：早产（PTD）是主要的 导致美国婴儿发病和死亡的原因，预防措施是 围产期保健的首要目标。最近的证据表明，有 怀孕期间阴道微生物群的改变之间存在密切关系 以及PTD的发生。然而，特定微生物在 PTD 中的作用 不太理解。该实验室最近的研究针对 识别与 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 微生物危险因素。我们的研究确定了两个关键人群 与 PTD 的发生有关。已经表明， 细菌磷脂酶 PLA2 的浓度在 20 之间增加 妊娠 37 周以下分娩的妇女则为妊娠 30 周。 PLA2 的增加与普雷沃氏菌的存在相关。作为的一部分 阴道微生物群。还值得注意的是，两者的存在 产生过氧化氢 (H2O2) 的乳酸菌和不产生 H2O2 的乳酸菌 乳酸杆菌同时作为阴道微生物群的一部分是一个危险因素 对于 PTD，与任一菌株本身的存在分开。 这一观察结果表明，菌株的组合可能会产生有害的影响。 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微生物数据 PTD 高风险女性和没有可识别 PTD 风险的女性， 确定统计模型是否能够基于以下条件预测 PTD 微生物学数据，为随后的研究做准备，其中女性 被该模型确定为有 PTD 风险的患者将得到治疗。此外， 将评估细菌引起 PTD 的实际机制，以便 确定任何干预研究的微生物目标。具体目标 对于该提案，1）完善从 对前三年收集的数据进行初步分析 研究并验证该模型在前瞻性预测期间预测 PID 临床试验，2）提高对特定作用的理解 PTD 中的细菌种类，特别是普雷沃氏菌 (Prevotella sp)，3) 使用分子分型 确定特定乳酸菌菌株是否更常见的方法 妊娠小于 37 周分娩的女性比妊娠 37 周分娩的女性 妊娠 37 周以上以及此类菌株是否是在怀孕期间获得的，以及 4) 确定乳酸菌菌株之间是否存在相互作用 使用培养的阴道上皮细胞对孕妇有害 体外暴露于体内发现的乳酸杆菌的组合。