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      Vaginal Microbiome Signature Is Associated With Spontaneous Preterm Delivery

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          Abstract

          Background: Preterm delivery (PTD) represents an important public health and therapeutic challenge. Despite the reported link between the composition of vaginal microbiome and PTD, previous studies were inconsistent in their conclusions and utilized non-uniform designs. We performed an independent case-control study carried out on the Slovenian population, where we re-evaluated the role of the vaginal microbiome in PTD.

          Methods: Vaginal microbiomes of pregnant women who delivered preterm were compared to those delivered at term to examine differences in the microbial richness, diversity, and differential abundance of specific taxa. We obtained vaginal swab samples from 155 Caucasian women who were classified as either term (≥38 0/7 weeks, n = 107) or preterm (≤36 6/7 weeks, n = 48) in exclusion of any other medical or obstetric conditions. The vaginal microbiomes of these women were characterized by 16S ribosomal RNA (rRNA) gene sequencing of the V3-V4 region on the MiSeq platform.

          Results: Women who experienced PTD had a higher microbial richness (Chao1, P = 0.011) and alpha diversity (Shannon, P = 0.00059) than women with term deliveries. We report that overall vaginal microbial community composition (beta-diversity) was significantly different by delivery gestational age category ( P WeightedUnifrac < 0.001). Women who delivered preterm had decreased Lactobacilli spp. abundance as well as increased abundance of Gardnerella and other bacterial vaginosis (BV) and aerobic vaginitis (AV) associated genera including Atopobium, Sneathia, Gemella, Megasphaera, Dorea, Streptococcus, and Escherichia/Shigella.

          Conclusions: In the present study, we provide further evidence that vaginal microbiome composition is associated with PTD.

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          Most cited references 29

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          A Metagenomic Approach to Characterization of the Vaginal Microbiome Signature in Pregnancy

          While current major national research efforts (i.e., the NIH Human Microbiome Project) will enable comprehensive metagenomic characterization of the adult human microbiota, how and when these diverse microbial communities take up residence in the host and during reproductive life are unexplored at a population level. Because microbial abundance and diversity might differ in pregnancy, we sought to generate comparative metagenomic signatures across gestational age strata. DNA was isolated from the vagina (introitus, posterior fornix, midvagina) and the V5V3 region of bacterial 16S rRNA genes were sequenced (454FLX Titanium platform). Sixty-eight samples from 24 healthy gravidae (18 to 40 confirmed weeks) were compared with 301 non-pregnant controls (60 subjects). Generated sequence data were quality filtered, taxonomically binned, normalized, and organized by phylogeny and into operational taxonomic units (OTU); principal coordinates analysis (PCoA) of the resultant beta diversity measures were used for visualization and analysis in association with sample clinical metadata. Altogether, 1.4 gigabytes of data containing >2.5 million reads (averaging 6,837 sequences/sample of 493 nt in length) were generated for computational analyses. Although gravidae were not excluded by virtue of a posterior fornix pH >4.5 at the time of screening, unique vaginal microbiome signature encompassing several specific OTUs and higher-level clades was nevertheless observed and confirmed using a combination of phylogenetic, non-phylogenetic, supervised, and unsupervised approaches. Both overall diversity and richness were reduced in pregnancy, with dominance of Lactobacillus species (L. iners crispatus, jensenii and johnsonii, and the orders Lactobacillales (and Lactobacillaceae family), Clostridiales, Bacteroidales, and Actinomycetales. This intergroup comparison using rigorous standardized sampling protocols and analytical methodologies provides robust initial evidence that the vaginal microbial 16S rRNA gene catalogue uniquely differs in pregnancy, with variance of taxa across vaginal subsite and gestational age.
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            Neurologic and developmental disability after extremely preterm birth. EPICure Study Group.

            Small studies show that many children born as extremely preterm infants have neurologic and developmental disabilities. We evaluated all children who were born at 25 or fewer completed weeks of gestation in the United Kingdom and Ireland from March through December 1995 at the time when they reached a median age of 30 months. Each child underwent a formal assessment by an independent examiner. Development was evaluated with use of the Bayley Scales of Infant Development, and neurologic function was assessed by a standardized examination. Disability and severe disability were defined by predetermined criteria. At a median age of 30 months, corrected for gestational age, 283 (92 percent) of the 308 surviving children were formally assessed. The mean (+/-SD) scores on the Bayley Mental and Psychomotor Developmental Indexes, referenced to a population mean of 100, were 84+/-12 and 87+/-13, respectively. Fifty-three children (19 percent) had severely delayed development (with scores more than 3 SD below the mean), and a further 32 children (11 percent) had scores from 2 SD to 3 SD below the mean. Twenty-eight children (10 percent) had severe neuromotor disability, 7 (2 percent) were blind or perceived light only, and 8 (3 percent) had hearing loss that was uncorrectable or required aids. Overall, 138 children had disability (49 percent; 95 percent confidence interval, 43 to 55 percent), including 64 who met the criteria for severe disability (23 percent; 95 percent confidence interval, 18 to 28 percent). When data from 17 assessments by local pediatricians were included, 155 of the 314 infants discharged (49 percent) had no disability. Severe disability is common among children born as extremely preterm infants.
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              The vaginal microbiome during pregnancy and the postpartum period in a European population

              The composition and structure of the pregnancy vaginal microbiome may influence susceptibility to adverse pregnancy outcomes. Studies on the pregnant vaginal microbiome have largely been limited to Northern American populations. Using MiSeq sequencing of 16S rRNA gene amplicons, we characterised the vaginal microbiota of a mixed British cohort of women (n = 42) who experienced uncomplicated term delivery and who were sampled longitudinally throughout pregnancy (8–12, 20–22, 28–30 and 34–36 weeks gestation) and 6 weeks postpartum. We show that vaginal microbiome composition dramatically changes postpartum to become less Lactobacillus spp. dominant with increased alpha-diversity irrespective of the community structure during pregnancy and independent of ethnicity. While the pregnancy vaginal microbiome was characteristically dominated by Lactobacillus spp. and low alpha-diversity, unlike Northern American populations, a significant number of pregnant women this British population had a L. jensenii-dominated microbiome characterised by low alpha-diversity. L. jensenii was predominantly observed in women of Asian and Caucasian ethnicity whereas L. gasseri was absent in samples from Black women. This study reveals new insights into biogeographical and ethnic effects upon the pregnancy and postpartum vaginal microbiome and has important implications for future studies exploring relationships between the vaginal microbiome, host health and pregnancy outcomes.
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                Author and article information

                Contributors
                Journal
                Front Med (Lausanne)
                Front Med (Lausanne)
                Front. Med.
                Frontiers in Medicine
                Frontiers Media S.A.
                2296-858X
                10 September 2019
                2019
                : 6
                Affiliations
                1Clinical Institute of Medical Genetics, University Medical Centre Ljubljana , Ljubljana, Slovenia
                2Division of Obstetrics and Gynecology, Department of Perinatology, University Medical Centre Ljubljana , Ljubljana, Slovenia
                3Department of Nutritional Sciences, University of Vienna , Vienna, Austria
                4Medical Faculty, University of Ljubljana , Ljubljana, Slovenia
                Author notes

                Edited by: Patrice Mathevet, Lausanne University Hospital (CHUV), Switzerland

                Reviewed by: Milos Stojanov, Lausanne University Hospital (CHUV), Switzerland; Fauziah Binti Jummaat, Management and Science University, Malaysia

                *Correspondence: Borut Peterlin borut.peterlin@ 123456guest.arnes.si

                This article was submitted to Obstetrics and Gynecology, a section of the journal Frontiers in Medicine

                Article
                10.3389/fmed.2019.00201
                6746969
                Copyright © 2019 Hočevar, Maver, Vidmar Šimic, Hodžić, Haslberger, Premru Seršen and Peterlin.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                Page count
                Figures: 3, Tables: 3, Equations: 0, References: 54, Pages: 12, Words: 8427
                Categories
                Medicine
                Original Research

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