Relationship between vaginal microbial dysbiosis, inflammation and pregnancy outcomes in cervical cerclage
File(s)KindingerSTM_2016_acceptedVersion.docx (8.1 MB)
Accepted version
Author(s)
Type
Journal Article
Abstract
Preterm birth, the leading cause of death in children under five, may be caused by inflammation triggered by ascending vaginal infection. About two million cervical cerclages are performed annually to prevent preterm birth. The procedure is thought to provide structural support and maintain the endocervical mucus plug as a barrier to ascending infection. Two types of suture material are used for cerclage: monofilament or multifilament braided. Braided sutures are most frequently used, though no evidence exists to favor them over monofilament sutures. In this study we assessed birth outcomes in a retrospective cohort of 678 women receiving cervical cerclage in 5 UK university hospitals and showed that braided cerclage was associated with increased intrauterine death (15% v 5%, P = 0.0001) and preterm birth (28% v 17%, P = 0.0006) compared to monofilament suture. To understand the potential underlying mechanism, we performed a prospective, longitudinal study of the vaginal microbiome in women at risk of preterm birth because of short cervical length (≤25 mm) who received braided (n=25) or monofilament (n=24) cerclage under otherwise comparable circumstances. Braided suture induced a persistent shift towards vaginal microbiome dysbiosis characterized by reduced Lactobacillus spp. and enrichment of pathobionts. Vaginal dysbiosis was associated with inflammatory cytokine and interstitial collagenase excretion into cervicovaginal fluid and premature cervical remodeling. Monofilament suture had comparatively minimal impact upon the vaginal microbiome and its interactions with the host. These data provide in vivo evidence that a dynamic shift of the human vaginal microbiome toward dysbiosis correlates with preterm birth.
Date Issued
2016-08-03
Date Acceptance
2016-06-23
Citation
Science Translational Medicine, 2016, 8 (350)
ISSN
1946-6242
Publisher
American Association for the Advancement of Science
Journal / Book Title
Science Translational Medicine
Volume
8
Issue
350
Copyright Statement
This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science Translational Medicine on Volume 8 number 350 4 Aug 2016, DOI: 10.1126/scitranslmed.aag1026
Sponsor
Medical Research Council (MRC)
Medical Research Council (MRC)
Grant Number
MR/L009226/1
MR/L009226/1
Subjects
11 Medical And Health Sciences
06 Biological Sciences
Publication Status
Published
Article Number
350ra102