Vaginal microbiota as a predictor of preterm birth: an observational cohort study

BackgroundIncreasing evidence link vaginal microbiota composition and preterm birth. However, the impact of the vaginal microbiota on preterm labor and premature rupture of membranes and on their outcome remain elusive, mainly because most studies are relatively small-sized. ObjectivesTo identify microbiota signatures of preterm labor, premature rupture of membranes, and spontaneous preterm birth. Study DesignWe conducted an observational, prospective, longitudinal cohort study from August 2018 until June 2023 in 3 maternity wards from university hospitals in the Paris, France, area. Women with singleton pregnancies were categorized in 3 groups including a control group, and 2 groups of increasing risk of preterm birth: preterm labor and preterm premature rupture of membranes. Demographic, clinical data, past medical and obstetrical history and pregnancy outcome were collected. Vaginal swabs were collected at admission and were analyzed using microbiological cultures. The association between bacterial species, the cohort groups, and spontaneous preterm birth was studied in univariate analyses. Adjusted odds ratio (aOR) and 95% confidence intervals (95% CI) were calculated in multivariable analyses. ResultsA total of 1,848 women were included, of whom 1,048 (56.7%) in the control group, 417 (22.6%) with preterm labor, and 383 (20.7%) with premature rupture of membranes. Together with demographic features such as ethnicity and obstetrical history, several vaginal microbiota signatures were identified in high-risk groups. In multivariable analysis, preterm labor was correlated with lactobacilli depletion (aOR 1.49, 95% CI 1.07-2.07), enterobacteria (aOR 1.91, 95% CI 1.40-2.62) and Gardnerella vaginalis (aOR 4.50, 95% CI 1.80-13.02), and premature rupture of membranes with lactobacilli depletion (aOR 2.10, 95% CI 1.52-2.89) and enterobacteria (aOR 2.39, 95% CI 1.75-3.26). Finally, lactobacilli depletion was a risk factor for spontaneous preterm birth (aOR 1.68, 95% CI 1.07-2.68). ConclusionsIn this large cohort, G. vaginalis was associated with preterm labor, while lactobacilli depletion and enterobacteria were risk factors for preterm labor and premature rupture of membranes. In addition, lactobacilli depletion was correlated with spontaneous preterm birth. Further studies are needed to address the benefits of adapted antibiotics and probiotics to restore a healthy microbiota for preventing preterm birth. At a glanceO_ST_ABSWhy was this study conducted?C_ST_ABSDespite the growing evidence of an association between vaginal microbiota composition and preterm birth, data remain elusive, because most studies were relatively small to examine cofounding factors. Moreover, longitudinal studies focusing on high-risk populations are lacking to transpose microbiological data into a clinical perspective. Key findingsIn a prospective cohort of over 1,800 pregnant women, using microbiological cultures of vaginal samples at admission and multivariable analyses adjusting for demographic and obstetrical factors, we identified lactobacilli depletion and enterobacteria as strong vaginal microbiota signatures of preterm labor and preterm rupture of membranes as compared to controls. Importantly, lactobacilli depletion constituted an independent risk factor for spontaneous preterm birth. What does this add to what is known?We confirm the implication of vaginal microbiota in preterm birth and highlight the importance of lactobacilli in this outcome. Accurate characterization of vaginal microbiota at admission for preterm labor as well as preterm premature rupture of membranes could improve the management of these complications of pregnancy.