Characteristics of the vaginal microbiota associated with recurrent spontaneous preterm birth: a prospective cohort study

BackgroundFailure to understand the causes of recurrent spontaneous preterm birth (sPTB) has limited effective interventions. This study aimed to examine the relationship between the vaginal microbiota and the risk of sPTB recurrence.MethodsA prospective cohort study was conducted involving 152 pregnant women at a high risk of sPTB recurrence due to a history of sPTB between 16 and 27+6\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$<^>{+6}$$\end{document} weeks of gestation. Vaginal swabs were collected sequentially during early pregnancy (before 16 weeks) and late pregnancy (16-24 weeks) for 16 S ribosomal RNA (16 S rRNA) sequencing. The vaginal microbiota was subsequently compared between the recurrence and non-recurrence groups and the results analysed longitudinally.ResultsFifty-three (34.9%) participants experienced recurrent sPTB. Using random forest classification models and the linear discriminant analysis effect size method, Lactobacillus iners (L. iners) and Lactobacillus crispatus (L. crispatus) were identified as featured species that distinguished the recurrent group from the non-recurrent group. Following the hierarchical clustering of the vaginal microbiota into six community state types (CSTs), in the recurrent group, CST III (dominated by L. iners) was more prevalent in early pregnancy, whereas in late pregnancy, CST IVA and CST IVB (dominated by nonlactobacilli) were more prevalent. In contrast, CST IA (dominated by L. crispatus) was more prevalent in the non-recurrent group. The six CSTs was simplified into three vaginal community types, L. iners dominant type exhibited decreased instability and a greater likelihood of transitioning to the non-lactobacillus dominant type compared with other (non-iners) Lactobacilli dominant types.ConclusionsL. iners dominance in the vaginal microbiota before 16 weeks of gestation is associated with an increased risk of recurrent sPTB, partly because of its propensity to transition to an unfavorable non-Lactobacillus-dominant state. This finding highlights the potential role of vaginal microbiota as an intervention target for reducing the risk of recurrent sPTB in early pregnancy.