MacIntyre, DADAMacIntyreBrown, RichardRichardBrownMarchesi, JulianJulianMarchesiLee, YunYunLeeSmith, AnnAnnSmithLehne, BenjaminBenjaminLehneKindinger, LindsayLindsayKindingerTerzidou, VassoVassoTerzidouHolmes, ElaineElaineHolmesNicholson, JeremyJeremyNicholsonBennett, PhillipPhillipBennett2017-12-222018-01-242018-01-24BMC Medicine, 2018, 161741-7015http://hdl.handle.net/10044/1/55525Background: 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.© 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.Science & TechnologyLife Sciences & BiomedicineMedicine, General & InternalGeneral & Internal MedicineVaginal microbiotaPreterm birthPreterm prelabour rupture of membranesAntibioticsErythromycinNeonatal sepsisPregnancyPREMATURE RUPTUREBACTERIAL-VAGINOSISANTIMICROBIAL SUSCEPTIBILITYINTRAAMNIOTIC INFLAMMATIONCHILDHOOD OUTCOMESANTIBIOTIC-THERAPYPRELABOR RUPTUREMICROBIOTABIRTHCHORIOAMNIONITISAntibioticsErythromycinNeonatal sepsisPregnancyPreterm birthPreterm prelabour rupture of membranesVaginal microbiotaAdultAntibiotic ProphylaxisCohort StudiesDisease ProgressionDysbiosisErythromycinFemaleFetal Membranes, Premature RuptureHumansInfant, NewbornMicrobiotaNeonatal SepsisPregnancyPremature BirthPrenatal CareRNA, BacterialRNA, Ribosomal, 16SRisk FactorsVaginaVaginaHumansFetal Membranes, Premature RupturePremature BirthDisease ProgressionErythromycinRNA, BacterialRNA, Ribosomal, 16SAntibiotic ProphylaxisPrenatal CareRisk FactorsCohort StudiesPregnancyAdultInfant, NewbornFemaleMicrobiotaDysbiosisNeonatal Sepsis11 Medical and Health SciencesGeneral & Internal MedicineJournal Articlehttps://www.dx.doi.org/10.1186/s12916-017-0999-xhttps://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0999-xMR/L009226/1MR/L009226/1RDD03 79560BB/L020858/1BH124127RDA01 79560None GivenN/AEME/13/121/07RDA05 79560RDB04N/ASpringboardRDA27RDA27RDA27RDA27RDA02RF17/1011MR/R00875/1MR/R000875/1SSAT054EME/13/121/07