Vaginal dysbiosis increases risk of preterm fetal membrane rupture, neonatal sepsis and is exacerbated by erythromycin
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Published version
Author(s)
Type
Journal Article
Abstract
Background: Preterm prelabour rupture of the fetal membranes (PPROM) precedes 30% of preterm births and is a risk factor for early onset neonatal sepsis. As PPROM is strongly associated with ascending vaginal infection prophylactic antibiotics are widely used. The evolution of vaginal microbiota composition associated with PPROM and the impact of antibiotics on bacterial composition is unknown.
Methods: We prospectively assessed vaginal microbiota prior to and following PPROM using MiSeq-based sequencing of 16S rRNA gene amplicons and examined the impact of erythromycin prophylaxis on bacterial load and community structures.
Results: In contrast to pregnancies delivering at term, vaginal dysbiosis characterised by Lactobacillus spp. depletion, was present prior to the rupture of fetal membranes in approximately a third of cases (0% versus 27%, P= 0.026) and persisted following membrane rupture (31%, P= 0.005). Vaginal dysbiosis was exacerbated by erythromycin treatment (47%, P= 0.00009) particularly in women initially colonised by Lactobacillus species. Lactobacillus depletion and increased relative abundance of Sneathia spp. was associated with subsequent funisitis and early onset neonatal sepsis.
Conclusions:
Our data show that vaginal microbiota composition is a risk-factor for subsequent PPROM and is associated with adverse short-term maternal and neonatal outcomes. This highlights vaginal microbiota as a potentially modifiable antenatal risk factor for PPROM and suggests that routine use of erythromycin for PPROM be re-examined.
Methods: We prospectively assessed vaginal microbiota prior to and following PPROM using MiSeq-based sequencing of 16S rRNA gene amplicons and examined the impact of erythromycin prophylaxis on bacterial load and community structures.
Results: In contrast to pregnancies delivering at term, vaginal dysbiosis characterised by Lactobacillus spp. depletion, was present prior to the rupture of fetal membranes in approximately a third of cases (0% versus 27%, P= 0.026) and persisted following membrane rupture (31%, P= 0.005). Vaginal dysbiosis was exacerbated by erythromycin treatment (47%, P= 0.00009) particularly in women initially colonised by Lactobacillus species. Lactobacillus depletion and increased relative abundance of Sneathia spp. was associated with subsequent funisitis and early onset neonatal sepsis.
Conclusions:
Our data show that vaginal microbiota composition is a risk-factor for subsequent PPROM and is associated with adverse short-term maternal and neonatal outcomes. This highlights vaginal microbiota as a potentially modifiable antenatal risk factor for PPROM and suggests that routine use of erythromycin for PPROM be re-examined.
Date Issued
2018-01-24
Date Acceptance
2017-12-20
Citation
BMC Medicine, 2018, 16
ISSN
1741-7015
Publisher
BioMed Central
Journal / Book Title
BMC Medicine
Volume
16
Copyright Statement
© The Author(s). 2018 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
Biotechnology and Biological Sciences Research Council (BBSRC)
Medical Research Council (MRC)
Imperial College Healthcare NHS Trust- BRC Funding
Kristian Gerhard Jebsen Foundation
Bowel & Cancer Research
National Institute for Health Research
Imperial College Healthcare NHS Trust- BRC Funding
Imperial College Healthcare NHS Trust- BRC Funding
Seattle ChildrensHospital Research Foundation
The Academy of Medical Sciences
Imperial College Healthcare NHS Trust- BRC Funding
Imperial College Healthcare NHS Trust- BRC Funding
Imperial College Healthcare NHS Trust- BRC Funding
Imperial College Healthcare NHS Trust- BRC Funding
Imperial College Healthcare NHS Trust- BRC Funding
Imperial Health Charity
Medical Research Council
Medical Research Council (MRC)
Imperial College London
St Stephen's Aids Trust
National Institute for Health Research
Identifier
https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0999-x
Grant Number
MR/L009226/1
MR/L009226/1
RDD03 79560
BB/L020858/1
BH124127
RDA01 79560
None Given
N/A
EME/13/121/07
RDA05 79560
RDB04
N/A
Springboard
RDA27
RDA27
RDA27
RDA27
RDA02
RF17/1011
MR/R00875/1
MR/R000875/1
SSAT054
EME/13/121/07
Subjects
Science & Technology
Life Sciences & Biomedicine
Medicine, General & Internal
General & Internal Medicine
Vaginal microbiota
Preterm birth
Preterm prelabour rupture of membranes
Antibiotics
Erythromycin
Neonatal sepsis
Pregnancy
PREMATURE RUPTURE
BACTERIAL-VAGINOSIS
ANTIMICROBIAL SUSCEPTIBILITY
INTRAAMNIOTIC INFLAMMATION
CHILDHOOD OUTCOMES
ANTIBIOTIC-THERAPY
PRELABOR RUPTURE
MICROBIOTA
BIRTH
CHORIOAMNIONITIS
Antibiotics
Erythromycin
Neonatal sepsis
Pregnancy
Preterm birth
Preterm prelabour rupture of membranes
Vaginal microbiota
Adult
Antibiotic Prophylaxis
Cohort Studies
Disease Progression
Dysbiosis
Erythromycin
Female
Fetal Membranes, Premature Rupture
Humans
Infant, Newborn
Microbiota
Neonatal Sepsis
Pregnancy
Premature Birth
Prenatal Care
RNA, Bacterial
RNA, Ribosomal, 16S
Risk Factors
Vagina
Vagina
Humans
Fetal Membranes, Premature Rupture
Premature Birth
Disease Progression
Erythromycin
RNA, Bacterial
RNA, Ribosomal, 16S
Antibiotic Prophylaxis
Prenatal Care
Risk Factors
Cohort Studies
Pregnancy
Adult
Infant, Newborn
Female
Microbiota
Dysbiosis
Neonatal Sepsis
11 Medical and Health Sciences
General & Internal Medicine
Publication Status
Published
Article Number
9
Date Publish Online
2018-01-24