Culture-based analysis of vaginal microbiota and its link to pregnancy outcomes: An observational cohort study in France

Rationale Increasing evidence links vaginal microbiota composition and preterm birth (PTB). However, most metagenomic studies are relatively small-sized, do not systematically adjust for confounders, and are difficult to transpose in clinical settings. Objective To identify, using routine vaginal microbiological cultures, signatures of preterm labor (PTL), preterm premature rupture of membranes (PPROM), and PTB. Methods We conducted an observational cohort study from August 2018 until June 2023 in France. Pregnant women were enrolled in three groups: control, PTL and PPROM. Demographic, clinical data, and pregnancy outcome were collected. Vaginal swabs were collected at enrollment and microbiological cultures were performed. The association between bacterial species and PTL, PPROM, and PTB was studied in univariate analyses. Adjusted odds ratio (aOR) and 95% confidence intervals (CI) were calculated in multivariable analyses adjusting for confounding variables. Results 1848 women were included: 1048 in the control group, 417 with PTL, and 383 with PPROM. Among women with PTL or PPROM, 328/646 (50.8%) spontaneously delivered preterm. Vaginal samples enriched in enterobacteria and in Gardnerella spp. were signatures of PTL. Lactobacilli depletion and enterobacteria enrichment were signatures of PPROM. In multivariable analysis, lactobacilli depletion was the strongest risk factor for spontaneous PTB (aOR 2.29, 95% CI 1.52-3.48). Conclusions Our study corroborates previous findings demonstrating the protective role of lactobacilli during pregnancy and highlights enterobacteria as signatures of PTL and PPROM. Furthermore, it provides perspectives for the management of women at high risk of PTB using standard microbiological techniques.