Vaginal microbiota in late pregnancy associates with the outcomes of planned induced labor: a multicenter prospective cohort study.

Abstract

Induction of labor is a commonly used obstetric method for terminating pregnancy in cases of delayed or expired pregnancy or complications, with cervical maturity being a key determinant of success. Balloon-induced labor is a safe, effective, and cost-effective induction of labor method. While clinical factors such as parity, cervical Bishop score, prepregnancy body mass index, are known to influence outcomes. Emerging evidence suggests that vaginal microbiota may also play a critical role through activation of local complement mediators and inflammatory signalling that accelerates cervical ripening. Additionally, genetic factors may influence both preterm birth risk and vaginal microbiota composition. However, the specific impact of vaginal microbiota and genetic factors on balloon-induced labor outcomes remains unclear and requires further investigation. To explore the impact of the vaginal microbiota prior to delivery on the maternal and fetal outcomes of planned induced labor through metagenomic sequencing and genome-wide association studies. A multicenter prospective cohort study was conducted from October 2022 to June 2024 across 5 hospitals, enrolling 635 pregnant women undergoing planned sequential induction of labor using cervical balloons combined with oxytocin. The clinical data throughout the entire pregnancy and labor period, as well as samples of vaginal and cervical secretions before the induction of labor, were collected. Firstly, the characteristics of the vaginal microbiota in all pregnant women were analyzed through metagenomic sequencing, and then the impact of vaginal microbiota differences on the maternal and fetal outcomes of planned induced labor was studied. Subsequently, a nested case-control study was performed, based on human whole genome sequencing combined with genome-wide association studies analysis on vaginal secretion samples, to investigate the role of genetic factors in planned induced labor. Finally, vaginal microbiota transplantation in pregnant rats was conducted to verify the effects of vaginal microbiota on the maternal and fetal outcomes of labor. Among the participants, 167 delivered within 24 hours, 318 delivered within 24-72 hours, 50 failed induction, and 100 underwent cesarean section for miscellaneous indications. Vaginal microbiota analysis in parturients revealed that the probability of delivery within 24 hours is negatively correlated with Lactobacillus iners (L. iners) abundance, while failed induction is negatively correlated with Ralstonia mannitolilytica abundance. Cesarean section probability is positively correlated with Lactobacillus crispatus (P=0.03). Additionally, the time from balloon placement to delivery is positively correlated with L. iners (P=0.002) and negatively correlated with Lactobacillus crispatus (P=0.08, not fully significant). Genome-wide association studies analysis shows that single-nucleotide polymorphisms associated with adverse pregnancy outcomes are mainly concentrated on chromosomes 1, 4, 8, and 10. Vaginal microbiota transplantation experiments showed that pregnant rats transplanted with vaginal bacteria from women who delivered within 24 hours had the shortest delivery time, while those transplanted with vaginal bacteria from women who failed to induced labor had the longest delivery time and some experienced dystocia. This study reveals that, in addition to genetic factors, the outcomes of planned labor induction, especially the total duration of labor and the success rate of induction, are closely related to the vaginal microbiota in women during the late stages of pregnancy. The study provides new evidence to explain the different outcomes of labor induction.