Dataset Information

High Diversity and Variability in the Vaginal Microbiome in Women following Preterm Premature Rupture of Membranes (PPROM): A Prospective Cohort Study.

ABSTRACT: To characterize the vaginal microbiota of women following preterm premature rupture of membranes (PPROM), and determine if microbiome composition predicts latency duration and perinatal outcomes.A prospective cohort study.Canada.Women with PPROM between 24+0 and 33+6 weeks gestational age (GA).Microbiome profiles, based on pyrosequencing of the cpn60 universal target, were generated from vaginal samples at time of presentation with PPROM, weekly thereafter, and at delivery.Vaginal microbiome composition, latency duration, gestational age at delivery, perinatal outcomes.Microbiome profiles were generated from 70 samples from 36 women. Mean GA at PPROM was 28.8 wk (mean latency 2.7 wk). Microbiome profiles were highly diverse but sequences representing Megasphaera type 1 and Prevotella spp. were detected in all vaginal samples. Only 13/70 samples were dominated by Lactobacillus spp. Microbiome profiles at the time of membrane rupture did not cluster by gestational age at PPROM, latency duration, presence of chorioamnionitis or by infant outcomes. Mycoplasma and/or Ureaplasma were detected by PCR in 81% (29/36) of women, and these women had significantly lower GA at delivery and correspondingly lower birth weight infants than Mycoplasma and/or Ureaplasma negative women.Women with PPROM had mixed, abnormal vaginal microbiota but the microbiome profile at PPROM did not correlate with latency duration. Prevotella spp. and Megasphaera type I were ubiquitous. The presence of Mollicutes in the vaginal microbiome was associated with lower GA at delivery. The microbiome was remarkably unstable during the latency period.

SUBMITTER: Paramel Jayaprakash T

PROVIDER: S-EPMC5115810 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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High Diversity and Variability in the Vaginal Microbiome in Women following Preterm Premature Rupture of Membranes (PPROM): A Prospective Cohort Study.

Paramel Jayaprakash Teenus T Wagner Emily C EC van Schalkwyk Julie J Albert Arianne Y K AY Hill Janet E JE Money Deborah M DM

PloS one 20161118 11

<h4>Objective</h4>To characterize the vaginal microbiota of women following preterm premature rupture of membranes (PPROM), and determine if microbiome composition predicts latency duration and perinatal outcomes.<h4>Design</h4>A prospective cohort study.<h4>Setting</h4>Canada.<h4>Population</h4>Women with PPROM between 24+0 and 33+6 weeks gestational age (GA).<h4>Methods</h4>Microbiome profiles, based on pyrosequencing of the cpn60 universal target, were generated from vaginal samples at time o ...[more]

PMID: 27861554

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Project description:BackgroundPreterm premature rupture of membranes (PPROM) is the leading identifiable cause of preterm birth, a complication that is more common in African Americans. Attempts to identify genetic loci associated with preterm birth using genome-wide association studies (GWAS) have only been successful with large numbers of cases and controls, and there has yet to be a convincing genetic association to explain racial/ethnic disparities. Indeed, the search for ancestry-specific variants associated with preterm birth has led to the conclusion that spontaneous preterm birth could be the consequence of multiple rare variants. The hypothesis that preterm birth is due to rare genetic variants that would go undetected in standard GWAS has been explored in the present study. The detection and validation of these rare variants present challenges because of the low allele frequency. However, some success in the identification of fetal loci/genes associated with preterm birth using whole genome sequencing and whole exome sequencing (WES) has recently been reported. While encouraging, this is currently an expensive technology, and methods to leverage the sequencing data to quickly identify and cost-effectively validate variants are needed.MethodsWe developed a WES data analysis strategy based on neonatal genomic DNA from PPROM cases and term controls that was unencumbered by preselection of candidate genes, and capable of identifying variants in African Americans worthy of focused evaluation to establish statistically significant associations.ResultsWe describe this approach and the identification of damaging nonsense variants of African ancestry in the DEFB1 and MBL2 genes that encode anti-microbial proteins that presumably defend the fetal membranes from infectious agents. Our approach also enabled us to rule out a likely contribution of a predicted damaging nonsense variant in the METTL7B gene.ConclusionsOur findings support the notion that multiple rare population-specific variants in the fetal genome contribute to preterm birth associated with PPROM.

Project description:OBJECTIVE: Bacterial colonization of the fetal membranes and its role in pathogenesis of membrane rupture is poorly understood. Prior retrospective work revealed chorion layer thinning in preterm premature rupture of membranes (PPROM) subjects. Our objective was to prospectively examine fetal membrane chorion thinning and to correlate to bacterial presence in PPROM, preterm, and term subjects. STUDY DESIGN: Paired membrane samples (membrane rupture and membrane distant) were prospectively collected from: PPROM?=?14, preterm labor (PTL?=?8), preterm no labor (PTNL?=?8), term labor (TL?=?10), and term no labor (TNL?=?8), subjects. Sections were probed with cytokeratin to identify fetal trophoblast layer of the chorion using immunohistochemistry. Fluorescence in situ hybridization was performed using broad range 16 s ribosomal RNA probe. Images were evaluated, chorion and choriodecidua were measured, and bacterial fluorescence scored. Chorion thinning and bacterial presence were compared among and between groups using Student's t-test, linear mixed effect model, and Poisson regression model (SAS Cary, NC). RESULTS: In all groups, the fetal chorion cellular layer was thinner at rupture compared to distant site (147.2 vs. 253.7 µm, p<0.0001). Further, chorion thinning was greatest among PPROM subjects compared to all other groups combined, regardless of site sampled [PPROM(114.9) vs. PTL(246.0) vs. PTNL(200.8) vs. TL(217.9) vs. TNL(246.5)]. Bacteria counts were highest among PPROM subjects compared to all other groups regardless of site sampled or histologic infection [PPROM(31) vs. PTL(9) vs. PTNL(7) vs. TL(7) vs. TNL(6)]. Among all subjects at both sites, bacterial counts were inversely correlated with chorion thinning, even excluding histologic chorioamnionitis (p<0.0001 and p?=?0.05). CONCLUSIONS: Fetal chorion was uniformly thinner at rupture site compared to distant sites. In PPROM fetal chorion, we demonstrated pronounced global thinning. Although cause or consequence is uncertain, bacterial presence is greatest and inversely correlated with chorion thinning among PPROM subjects.

Dataset Information

High Diversity and Variability in the Vaginal Microbiome in Women following Preterm Premature Rupture of Membranes (PPROM): A Prospective Cohort Study.

Publications

High Diversity and Variability in the Vaginal Microbiome in Women following Preterm Premature Rupture of Membranes (PPROM): A Prospective Cohort Study.

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