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Relationship between vaginal microbial dysbiosis, inflammation, and pregnancy outcomes in cervical cerclage

McDonald, Julie A.K.; Kindinger, Lindsay M.; MacIntyre, David A.; Lee, Yun S.; Marchesi, Julian R.; Smith, Ann; Terzidou, Vasso; Cook, Joanna R.; Lees, Christoph; Israfil-Bayli, Fidan; Faiza, Yazmin; Toozs-Hobson, Philip; Slack, Mark; Cacciatore, Stefano; Holmes, Elaine; Nicholson, Jeremy K.; Teoh, T. G.; Bennett, Phillip R.

Authors

Julie A.K. McDonald

Lindsay M. Kindinger

David A. MacIntyre

Yun S. Lee

Julian R. Marchesi

Ann Smith

Vasso Terzidou

Joanna R. Cook

Christoph Lees

Fidan Israfil-Bayli

Yazmin Faiza

Philip Toozs-Hobson

Mark Slack

Stefano Cacciatore

Elaine Holmes

Jeremy K. Nicholson

T. G. Teoh

Phillip R. Bennett



Abstract

Preterm birth, the leading cause of death in children under 5 years, may be caused by inflammation triggered by ascending vaginal infection. About 2 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, although no evidence exists to favor them over monofilament sutures. We assessed birth outcomes in a retrospective cohort of 678 women receiving cervical cerclage in five UK university hospitals and showed that braided cerclage was associated with increased intrauterine death (15% versus 5%; P = 0.0001) and preterm birth (28% versus 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 comparable circumstances. Braided suture induced a persistent shift toward 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.

Citation

McDonald, J. A., Kindinger, L. M., MacIntyre, D. A., Lee, Y. S., Marchesi, J. R., Smith, A., …Bennett, P. R. (2016). Relationship between vaginal microbial dysbiosis, inflammation, and pregnancy outcomes in cervical cerclage. Science Translational Medicine, 8(350), https://doi.org/10.1126/scitranslmed.aag1026

Journal Article Type Article
Acceptance Date Jun 23, 2016
Online Publication Date Aug 3, 2016
Publication Date Aug 3, 2016
Deposit Date Oct 2, 2019
Publicly Available Date Oct 4, 2019
Journal Science Translational Medicine
Print ISSN 1946-6234
Electronic ISSN 1946-6242
Publisher American Association for the Advancement of Science
Peer Reviewed Peer Reviewed
Volume 8
Issue 350
Article Number 350ra102
DOI https://doi.org/10.1126/scitranslmed.aag1026
Public URL https://uwe-repository.worktribe.com/output/3453599
Related Public URLs https://spiral.imperial.ac.uk:8443/handle/10044/1/34435

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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





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