The interaction between vaginal microbiota, cervical length and vaginal progesterone treatment for preterm birth risk
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Published version
Author(s)
Type
Journal Article
Abstract
Background:
Preterm birth is the primary cause of infant death worldwide.
A short cervix in the second trimester of pregnancy is a risk factor for preterm birth. In specific patient cohorts, vaginal progesterone
reduces this risk. Using 16S rRNA gene sequencing we
undertook a prospective study in women at risk of preterm birth
(n=161) to assess 1) the relationship between vaginal microbiota
and cervical length in the second trimester and preterm birth-risk, and 2) the impact of vaginal progesterone on vaginal
bacterial communities in women with a short cervix.
Results:
Lactobacillus iners dominance at 16 weeks gestation was significantly
associated with both a short cervix <25mm (n=15, P<0.05), and
preterm birth <34+0 weeks (n=18, 38P<0.01; 69% PPV).
In contrast, L. crispatus dominance was highly predictive of term birth (n=127, 98% PPV). Cervical shortening and preterm birth
were not associated with vaginal dysbiosis. A longitudinal characterization of vaginal microbiota (<18, 22, 28 and 34 weeks)
was then undertaken in women receiving vaginal progesterone (400mg/OD, n=25) versus controls (n=42).
Progesterone did not alter vaginal bacterial community structure
nor reduce L. iners-associated preterm birth (<34 weeks).
Conclusions:
L. iners dominance of the vaginal microbiota at 16 weeks gestation is a risk factor for preterm birth, whereas L. crispatus dominance is protective against preterm birth. Vaginal progesterone does not
appear to impact the pregnancy vaginal microbiota. Patients and clinicians who may be concerned about ‘infection risk’ associated with use of a vaginal pessary during high-risk pregnancy can be reassured.
Preterm birth is the primary cause of infant death worldwide.
A short cervix in the second trimester of pregnancy is a risk factor for preterm birth. In specific patient cohorts, vaginal progesterone
reduces this risk. Using 16S rRNA gene sequencing we
undertook a prospective study in women at risk of preterm birth
(n=161) to assess 1) the relationship between vaginal microbiota
and cervical length in the second trimester and preterm birth-risk, and 2) the impact of vaginal progesterone on vaginal
bacterial communities in women with a short cervix.
Results:
Lactobacillus iners dominance at 16 weeks gestation was significantly
associated with both a short cervix <25mm (n=15, P<0.05), and
preterm birth <34+0 weeks (n=18, 38P<0.01; 69% PPV).
In contrast, L. crispatus dominance was highly predictive of term birth (n=127, 98% PPV). Cervical shortening and preterm birth
were not associated with vaginal dysbiosis. A longitudinal characterization of vaginal microbiota (<18, 22, 28 and 34 weeks)
was then undertaken in women receiving vaginal progesterone (400mg/OD, n=25) versus controls (n=42).
Progesterone did not alter vaginal bacterial community structure
nor reduce L. iners-associated preterm birth (<34 weeks).
Conclusions:
L. iners dominance of the vaginal microbiota at 16 weeks gestation is a risk factor for preterm birth, whereas L. crispatus dominance is protective against preterm birth. Vaginal progesterone does not
appear to impact the pregnancy vaginal microbiota. Patients and clinicians who may be concerned about ‘infection risk’ associated with use of a vaginal pessary during high-risk pregnancy can be reassured.
Date Issued
2017-01-19
Date Acceptance
2016-12-15
Citation
Microbiome, 2017, 5 (6), pp.1-14
ISSN
2049-2618
Publisher
BioMed Central
Start Page
1
End Page
14
Journal / Book Title
Microbiome
Volume
5
Issue
6
Copyright Statement
© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Sponsor
Medical Research Council (MRC)
Medical Research Council (MRC)
Imperial College Healthcare NHS Trust- BRC Funding
Identifier
https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0223-9
Grant Number
MR/L009226/1
MR/L009226/1
RDD03 79560
Subjects
Science & Technology
Life Sciences & Biomedicine
Microbiology
Vaginal microbiome
Progesterone
Lactobacillus
Preterm birth
Cervical length
PLACEBO-CONTROLLED TRIAL
HUMAN MYOMETRIAL CELLS
BACTERIAL VAGINOSIS
HORMONAL CONTRACEPTION
PREGNANT-WOMEN
DOUBLE-BLIND
GENITAL-TRACT
FLORA
LACTOBACILLUS
DELIVERY
Cervical length
Lactobacillus
Preterm birth
Progesterone
Vaginal microbiome
Adult
Bacterial Load
Cervical Length Measurement
Cervix Uteri
Cross-Sectional Studies
Dysbiosis
Female
Humans
Lactobacillus
Microbiota
Pessaries
Pregnancy
Pregnancy Outcome
Pregnancy, High-Risk
Premature Birth
Progesterone
Prospective Studies
RNA, Ribosomal, 16S
Vagina
Young Adult
Cervix Uteri
Vagina
Humans
Lactobacillus
Premature Birth
Progesterone
RNA, Ribosomal, 16S
Pregnancy Outcome
Prospective Studies
Cross-Sectional Studies
Pessaries
Pregnancy
Pregnancy, High-Risk
Adult
Female
Cervical Length Measurement
Young Adult
Bacterial Load
Microbiota
Dysbiosis
0602 Ecology
0605 Microbiology
1108 Medical Microbiology
Publication Status
Published
Article Number
6
Date Publish Online
2017-01-19