Mycoplasma genitalium, differentiated Ureaplasma species, and pregnancy outcomes

生殖支原体、分化解脲支原体种类和妊娠结局

• 批准号: 8803883
• 负责人: CATHERINE L HAGGERTY
• 金额: $ 21.07万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-25 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8803883
• 关键词: Accounting; Address; Archives; Bacteria; Collaborations; Conceptions; Conflict (Psychology); Data; Detection; Disease; Endometritis; Etiology; Exploratory/Developmental Grant; Family health status; First Pregnancy Trimester; General Population; Goals; Histologic; India; Infection; Intervention; Lead; Link; Marriage; Measures; Mediating; Mollicutes; Morbidity - disease rate; Multiple Pregnancy; Mycoplasma genitalium; Nested Case-Control Study; Parents; Pelvic Inflammatory Disease; Placenta; Plague; Population; Postpartum Period; Pregnancy; Pregnancy Outcome; Premature Birth; Recruitment Activity; Reporting; Reproductive Tract Infections; Research; Risk; Role; Rural; Sampling; Second Pregnancy Trimester; Specimen; Spontaneous abortion; Testing; Third Pregnancy Trimester; Time; Translating; Undifferentiated; Universities; Ureaplasma; Ureaplasma Infections; Urethritis; Vagina; Visit; Woman; adverse pregnancy outcome; base; clinical practice; co-infection; cohort; design; effective intervention; experience; infant morbidity; innovation; intraamniotic infection; maternal morbidity; men; microorganism; novel; pathogen; population based; prenatal; prevent; prospective; public health relevance; reproductive tract; screening; successful intervention

DESCRIPTION (provided by applicant): Preterm birth (PTB) and spontaneous abortion (SAB) are common adverse pregnancy outcomes which account for a significant amount of maternal and infant morbidity worldwide. Although ascending genital tract infection has been implicated in approximately half of spontaneous PTB (sPTB) cases and has been linked in some studies with SAB, the microbiologic etiology of these adverse pregnancy outcomes remains poorly understood. The overall goal of our study is to determine the role of pre-pregnancy and prenatal vaginal infections with Mollicutes including fastidious Mycoplasma genitalium (MG) and the newly differentiated Ureaplasma spp. termed U. urealyticum (UU) and U. parvum (UP) in PTB and SAB. Despite the demonstrated ability of MG to infect the upper genital tract and cause pelvic inflammatory disease, very little is known about the effect of MG in pregnancy. Studies assessing the association of ureaplasmas with adverse pregnancy outcomes have been conflicting, yet are confounded with the realization that the ureaplasmas formerly called U. urealyticum were actually composed of two distinct species, UU and UP. Indeed, UU has been associated with nongonococcal urethritis in men, whereas UP has been shown in several NGU studies to be nonpathogenic. Similarly, our group was the first to recently report that UU, but not UP is associated with endometritis in women. As little is known about the effect of MG and differentiated Ureaplasma spp. on pregnancy outcomes, we propose to test the hypothesis that women testing positive for MG, UU, and UP will have increased risks of adverse pregnancy outcomes, including STB and PTB. Further, we hypothesize that the relationships between infection and pregnancy outcomes will be strongest for women with persistent infections, co-infections, and greater bacterial load. Additionally, we will examine chorioamnionitis as a mediating factor between each bacteria and spontaneous PTB. To achieve this, we propose the first comprehensive study of MG and the newly differentiated Ureaplasma spp. utilizing quantitative PCR to assess exposure at various time-points during pregnancy as well as the pre-pregnancy period among 151 women who delivered preterm, 141 women who experienced a SAB, and 302 control women who delivered at term, nested within the prospective Longitudinal Indian Family HEalth (LIFE) Study conducted in collaboration by SHARE India and the University of Pittsburgh in a rural region near Hyderabad, India. In the longitudinal cohort parent study, 1227 women were recruited before pregnancy and followed through conception, pregnancy, delivery and postpartum, and vaginal specimens were archived pre-pregnancy, at 5 weeks gestation, at first and second trimester visits, delivery and postpartum. A major innovation is our design within an Indian population which attempts conception soon after marriage allows us to feasibly and efficiently study pre-pregnancy exposures. This design is also particularly novel for the study of SAB, which has been traditionally plagued by the inability to feasibly recruit a population based sample of women pre-conception or very early in pregnancy, before many SABs occur. Our study is important, as MG and Ureaplasma infections are common, screening is not routine, and interventions based on our findings may prevent significant pregnancy morbidity in India, the U.S., and elsewhere. Further, as ureasplasmas are common in the vaginal flora of asymptomatic women who deliver to term as well as women who experience adverse pregnancy outcomes, screening for undifferentiated and unquantified ureaplasmas in the general population is unlikely to have any utility. By determining whether the risks of SAB and PTB differ by specie or bacterial load and utilizing vaginal samples collected at multiple pregnancy time points, findings from our research will be readily translated into clinical practice through screening of specimens collected non-invasively and early enough to allow for effective intervention.

描述（由申请人提供）：早产（PTB）和自然流产（SAB）是常见的不良妊娠结局，是全球孕产妇和婴儿发病率的重要原因。虽然上行性生殖道感染与大约一半的自发性PTB（sPTB）病例有关，并且在一些研究中与SAB有关，但这些不良妊娠结局的微生物学病因仍知之甚少。我们研究的总体目标是确定妊娠前和产前阴道感染柔膜菌的作用，包括苛养生殖支原体（MG）和新分化的脲原体属。称为U。解脲脲原体（UU）和解脲脲原体（U.在PTB和SAB中存在小孢子虫（UP）。尽管已证实MG能够感染上生殖道并引起盆腔炎，但对MG在妊娠期的影响知之甚少。评估脲原体与不良妊娠结局相关性的研究一直存在矛盾，但与脲原体以前被称为U。解脲支原体实际上是由两个不同的物种组成，UU和UP。事实上，UU与男性非淋菌性尿道炎有关，而UP在几项NGU研究中显示为非致病性。同样，我们的小组是最近第一个报告UU，但不是 UP与女性尿道炎有关。由于对MG和分化的脲原体属的影响知之甚少。在妊娠结局方面，我们建议检验以下假设：MG、UU和UP检测阳性的妇女发生不良妊娠结局（包括STB和PTB）的风险增加。此外，我们假设感染和妊娠结局之间的关系对于持续感染、合并感染和细菌负荷更大的女性来说是最强的。此外，我们将研究绒毛膜炎作为每种细菌和自发性PTB之间的介导因素。为了实现这一目标，我们提出了第一个全面的研究MG和新分化的脲原体属。利用定量PCR评估151名早产妇女、141名经历SAB的妇女和302名足月分娩的对照妇女在怀孕期间和怀孕前不同时间点的暴露情况，这些妇女嵌套在由印度SHARE和匹兹堡大学在海得拉巴附近农村地区合作进行的前瞻性纵向印度家庭健康（LIFE）研究中，印度在纵向队列父母研究中，招募了1227名妇女，在怀孕前，并通过受孕，怀孕，分娩和产后进行随访，并在怀孕前，怀孕5周，妊娠早期和中期访视，分娩和产后对阴道标本进行存档。一个主要的创新是我们在印度人口中的设计，该设计试图在婚后不久受孕，使我们能够切实有效地研究孕前暴露。这种设计对于SAB的研究来说也是特别新颖的，SAB的研究传统上一直受到无法 在许多SAB发生之前，可行地招募基于人群的怀孕前或怀孕早期妇女样本。我们的研究很重要，因为MG和支原体感染很常见，筛查不是常规的，基于我们研究结果的干预措施可能会预防印度，美国，和其他地方。此外，由于脲原体常见于足月分娩的无症状妇女以及经历不良妊娠结局的妇女的阴道植物群中，因此在一般人群中筛查未分化和未定量的脲原体不太可能有任何效用。通过确定SAB和PTB的风险是否因物种或细菌载量而不同，并利用在多个妊娠时间点收集的阴道样本，我们的研究结果将很容易转化为临床应用。 通过筛选非侵入性收集的标本，及早采取有效干预措施。