Vaginal bacterial load in the second trimester is associated with early preterm birth recurrence: a nested case-control study
Goodfellow, Laura; Verwijs, Marijn C; Care, Angharad; Sharp, Andrew; Ivandic, Jelena; Poljak, Borna; Roberts, Devender; Bronowski, Christina; Gill, A Christina; Darby, Alistair C; Alfirevic, Ana; Muller-Myhsok, Bertram; Alfirevic, Zarko; van de Wijgert, Janneke H H M
(2021) BJOG - An International Journal of Obstetrics and Gynaecology, volume 128, issue 13, pp. 2061 - 2072
(Article)
Abstract
Objective: To assess the association between vaginal microbiome (VMB) composition and recurrent early spontaneous preterm birth (sPTB)/preterm prelabour rupture of membranes (PPROM). Design: Nested case–control study. Setting: UK tertiary referral hospital. Sample: High-risk women with previous sPTB/PPROM <34 +0 weeks’ gestation who had a recurrence (n = 22) or delivered at ≥37
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+0 weeks without PPROM (n = 87). Methods: Vaginal swabs collected between 15 and 22 weeks’ gestation were analysed by 16S rRNA gene sequencing and 16S quantitative PCR. Main outcome measure: Recurrent early sPTB/PPROM. Results: Of the 109 high-risk women, 28 had anaerobic vaginal dysbiosis, with the remainder dominated by lactobacilli (Lactobacillus iners 36/109, Lactobacillus crispatus 23/109, or other 22/109). VMB type and diversity were not associated with recurrence. Women with a recurrence, compared to those without, had a higher median vaginal bacterial load (8.64 versus 7.89 log 10 cells/mcl, adjusted odds ratio [aOR] 1.90, 95% CI 1.01–3.56, P = 0.047) and estimated Lactobacillus concentration (8.59 versus 7.48 log 10 cells/mcl, aOR 2.35, (95% CI 1.20–4.61, P = 0.013). A higher recurrence risk was associated with higher median bacterial loads for each VMB type after stratification, although statistical significance was reached only for L. iners domination (aOR 3.44, 95% CI 1.06–11.15, P = 0.040). Women with anaerobic dysbiosis or L. iners domination had a higher median vaginal bacterial load than women with a VMB dominated by L. crispatus or other lactobacilli (8.54, 7.96, 7.63, and 7.53 log 10 cells/mcl, respectively). Conclusions: Vaginal bacterial load is associated with early sPTB/PPROM recurrence. Domination by lactobacilli other than L. iners may protect women from developing high bacterial loads. Future PTB studies should quantify vaginal bacteria and yeasts. Tweetable abstract: Increased vaginal bacterial load in the second trimester may be associated with recurrent early spontaneous preterm birth.
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Keywords: Lactobacillus, preterm premature rupture of membranes, spontaneous preterm birth, vaginal microbiome, Obstetrics and Gynaecology, Journal Article
ISSN: 1470-0328
Publisher: Wiley-Blackwell
Note: Funding Information: LG, AC, AS, AA, BM‐M, AA, ZA and JW received a grant from Wellbeing of Women charity to establish the Harris Wellbeing Research Centre that funded the submitted work. MW, aCG, CB, DR, JI and BP received no support from any organisation for the submitted work. All authors declare no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. Completed disclosure of interest forms are available to view online as supporting information. Funding Information: The prospective cohort study was funded by Wellbeing of Women as part of a charitable donation from Lord and Lady Harris to establish the Harris-Wellbeing PTB Research Centre, University of Liverpool. This covered administrative costs, laboratory analysis, salary for AC, study support costs for AC and LG. No additional funding was used. Wellbeing of Women were not involved in the conduct of the research or writing the paper. We would like to thank all participants for their enthusiastic involvement in the study, in particular members of the Harris-Wellbeing Patient and Public Engagement group. We would also like to thank the Liverpool Women?s Hospital for hosting the research, Tracy Ricketts at the Liverpool Women?s Hospital for administrative support, University of Liverpool Centre for Genomic Research staff for 16S sequencing, and Jacques Ravel and Mike Humphrys at the University of Maryland School of Medicine, Institute for Genome Sciences, for the 16S qPCR assays. Publisher Copyright: © 2021 John Wiley & Sons Ltd.
(Peer reviewed)