Mycoplasma genitalium, differentiated Ureaplasma species, and pregnancy outcomes

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，在全世界孕产妇和婴儿发病率中占很大比例。尽管大约一半的自发性PTB （sPTB）病例与上行生殖道感染有关，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病因学仍然知之甚少。我们的研究的总体目标是确定孕前和产前阴道感染的Mollicutes，包括生殖道支原体（MG）和新分化的脲原体，称为解脲支原体（UU）和细小脲原体（UP）在PTB和SAB中的作用。尽管已证实MG可感染上生殖道并引起盆腔炎，但对MG在妊娠期的作用知之甚少。评估脲原体与不良妊娠结局之间关系的研究一直存在矛盾，但人们认识到，以前被称为解脲脲原体的脲原体实际上由两个不同的物种组成，即UU和UP。事实上，UU与男性非淋球菌性尿道炎有关，而UP在一些NGU研究中已被证明是非致病性的。同样，我们的小组是最近第一个报告UU的，但不是

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.