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

Background: Preterm birth (birth before 37 weeks of gestational age) is a frequent and severe adverse pregnancy outcome. Despite the growing number of scientific studies highlighting the link between vaginal microbiota composition and adverse pregnancy outcomes, data remain controversial. Objectives: To identify microbiota signatures of preterm labor and premature rupture of outer membranes; to determine microbiological risk factors for preterm birth. Study Design: We 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 were categorized in 4 groups including a control group, and 3 groups of increasing risk of intrauterine infection and preterm birth: prelabor rupture of membranes at term, 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 culturomics. The association between bacterial species and the cohort groups and eventually preterm birth was studied in univariate analyses. Adjusted odds ratio (aOR) and 95% confidence intervals (95% CI) were calculated in multivariable analyses. Results: A total of 2,476 women were included, of whom 1,068 (43.1%) in the control group, 477 (19.3%) with term premature rupture of outer membranes, 495 (20.0%) with preterm labor, and 436 (17.6%) with preterm premature rupture of outer membranes. Together with demographic features such as ethnicity and obstetrical history, several vaginal microbiota signatures were identified as correlated with pregnancy outcome. In multivariable analysis, prelabor rupture of membranes at term was associated with enterobacteria (aOR 1.97, 95% CI 1.46-2.65) and Gardnerella vaginalis (aOR 5.19, 95% CI 2.22-13.78); preterm labor with lactobacilli depletion (aOR 1.49, 95% CI 1.08-2.06), enterobacteria (aOR 1.86, 95% CI 1.36-2.53) and G. vaginalis (aOR 4.62, 95% CI 1.86-13.34); preterm premature rupture of membranes with lactobacilli depletion (aOR 2.04, 95% CI 1.49-2.80) and enterobacteria (aOR 2.38, 95% CI 1.74-3.24). Finally, together with gestational diabetes, lactobacilli depletion and enterobacteria both represented risk factors for preterm birth, especially in singleton pregnancies (aOR 1.54, 95% CI 1.05-2.28 and aOR 1.62, 95% CI 1.11-2.36, respectively). Conclusions: In this large cohort study, we identified on the one hand, G. vaginalis as associated with prelabor rupture of membranes at term and preterm labor, and on the other hand, lactobacilli depletion and enterobacteria as risk factors for preterm labor, preterm premature rupture of outer membranes, and preterm birth, emphasizing the importance of a healthy microbiota in pregnancy outcome. Further studies are needed to address the benefits of adapted antibiotic prophylaxes and probiotics aiming at restoring a healthy microbiota in reducing the risk of preterm birth.