Vaginal bacterial load in the second trimester is associated with early preterm birth recurrence: a nested case-control study

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 +0 weeks without PPROM (n=87). Methods Vaginal swabs collected between 15-22 weeks gestation were analysed by 16S rRNA gene sequencing and 16S quantitative PCR. Main outcome measure Recurrent early sPTB/PPROM. Results 28/109 high-risk women had anaerobic vaginal dysbiosis, with the remainder dominated by lactobacilli ( L. iners 36/109, L. crispatus 23/109, or other 22/109). VMB type, diversity, and stability were not associated with recurrence. Women with a recurrence, compared to those without, had a higher median vaginal bacterial load (8.64 vs. 7.89 log 10 cells/μl, adjusted odds ratio (aOR)=1.90, 95% confidence interval (CI)=1.01-3.56, p=0.047) and estimated Lactobacillus concentration (8.59 vs. 7.48 log 10 cells/μl, aOR=2.35, 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, 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/μl, 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. Funding Wellbeing of Women, London, UK Tweetable abstract Increased vaginal bacterial load in the second trimester may be associated with recurrent early spontaneous preterm birth.