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早期妊娠阴道微生物群趋势与早产

Early pregnancy vaginal microbiome trends and preterm birth.

作者信息

Stout Molly J, Zhou Yanjiao, Wylie Kristine M, Tarr Phillip I, Macones George A, Tuuli Methodius G

机构信息

Department of Obstetrics and Gynecology, Washington University in St Louis School of Medicine, St. Louis, MO.

Department of Pediatrics, Washington University in St Louis School of Medicine, St. Louis, MO; The McDonnell Genome Institute, Washington University in St Louis School of Medicine, St. Louis, MO.

出版信息

Am J Obstet Gynecol. 2017 Sep;217(3):356.e1-356.e18. doi: 10.1016/j.ajog.2017.05.030. Epub 2017 May 23.

Abstract

BACKGROUND

Despite decades of attempts to link infectious agents to preterm birth, an exact causative microbe or community of microbes remains elusive. Nonculture 16S ribosomal RNA gene sequencing suggests important racial differences and pregnancy specific changes in the vaginal microbial communities. A recent study examining the association of the vaginal microbiome and preterm birth documented important findings but was performed in a predominantly white cohort. Given the important racial differences in bacterial communities within the vagina as well as persistent racial disparities in preterm birth, it is important to examine cohorts with varied demographic compositions.

OBJECTIVE

To characterize vaginal microbial community characteristics in a large, predominantly African-American, longitudinal cohort of pregnant women and test whether particular vaginal microbial community characteristics are associated with the risk for subsequent preterm birth.

STUDY DESIGN

This is a nested case-control study within a prospective cohort study of women with singleton pregnancies, not on supplemental progesterone, and without cervical cerclage in situ. Serial mid-vaginal swabs were obtained by speculum exam at their routine prenatal visits. Sequencing of the V1V3 region of the 16S rRNA gene was performed on the Roche 454 platform. Alpha diversity community characteristics including richness, Shannon diversity, and evenness as well as beta diversity metrics including Bray Curtis Dissimilarity and specific taxon abundance were compared longitudinally in women who delivered preterm to those who delivered at term.

RESULTS

A total of 77 subjects contributed 149 vaginal swabs longitudinally across pregnancy. Participants were predominantly African-American (69%) and had a preterm birth rate of 31%. In subjects with subsequent term delivery, the vaginal microbiome demonstrated stable community richness and Shannon diversity, whereas subjects with subsequent preterm delivery had significantly decreased vaginal richness, diversity, and evenness during pregnancy (P < .01). This change occurred between the first and second trimesters. Within-subject comparisons across pregnancy showed that preterm birth is associated with increased vaginal microbiome instability compared to term birth. No distinct taxa were associated with preterm birth.

CONCLUSION

In a predominantly African-American population, a significant decrease of vaginal microbial community richness and diversity is associated with preterm birth. The timing of this suppression appears early in pregnancy, between the first and second trimesters, suggesting that early gestation may be an ecologically important time for events that ordain subsequent term and preterm birth outcomes.

摘要

背景

尽管数十年来一直试图将感染因子与早产联系起来,但确切的致病微生物或微生物群落仍难以捉摸。非培养16S核糖体RNA基因测序表明,阴道微生物群存在重要的种族差异以及与妊娠相关的特定变化。最近一项研究阴道微生物群与早产之间关联的研究记录了重要发现,但该研究主要在白人队列中进行。鉴于阴道内细菌群落存在重要的种族差异以及早产方面持续存在的种族差异,研究不同人口构成的队列很重要。

目的

描述一个以非裔美国人为主的大型孕妇纵向队列中的阴道微生物群落特征,并测试特定的阴道微生物群落特征是否与随后早产的风险相关。

研究设计

这是一项嵌套在单胎妊娠、未使用补充孕酮且未进行宫颈环扎术的前瞻性队列研究中的病例对照研究。在常规产前检查时通过窥阴器检查获取系列阴道中段拭子。在罗氏454平台上对16S rRNA基因的V1V3区域进行测序。将早产孕妇与足月分娩孕妇纵向比较α多样性群落特征,包括丰富度、香农多样性和均匀度,以及β多样性指标,包括布雷-柯蒂斯差异和特定分类群丰度。

结果

共有77名受试者在整个孕期纵向提供了149份阴道拭子。参与者主要是非裔美国人(69%),早产率为31%。在随后足月分娩的受试者中,阴道微生物群显示出稳定的群落丰富度和香农多样性,而随后早产的受试者在孕期阴道丰富度、多样性和均匀度显著降低(P < 0.01)。这种变化发生在孕早期和孕中期之间。孕期个体内比较显示,与足月分娩相比,早产与阴道微生物群不稳定性增加有关。没有明显的分类群与早产相关。

结论

在以非裔美国人为主的人群中,阴道微生物群落丰富度和多样性的显著降低与早产有关。这种抑制的时间似乎在孕期早期,即孕早期和孕中期之间,这表明妊娠早期可能是决定随后足月分娩和早产结局的生态重要时期。

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