The vaginal microbiome and the risk of preterm birth: a systematic review and network meta-analysis.

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• The diversity of the vaginal microbiome is reported to play a part in the risk of preterm births.
• Practitioners could consider testing the virginal microbiome for low Lactobacilli or the dominance of Gardnerella and Prevotella and then recommending a probiotic supplement to pregnant patients who have low Lactobacilli vaginal microbiome.

Introduction

A systematic review and network meta-analysis was conducted to investigate the association between vaginal microbiome and risk of preterm births.

Methodology

• Seventeen longitudinal cohort studies were included. Seven originated from North America, three from Europe, two from South America, three from Asia, and two from Africa. The number of pregnancies per study ranged between 38 and 539, with 8 and 107 preterm births. 16S Sequencing techniques were used to identify the microbial species. Preterm birth was defined as birth before 37 weeks of gestation.
• Microbiome community state types (CSTs) were grouped into five categories based on dominating species: L. crispatus, L. gasseri, L. iners,“low-lactobacilli” and L. jensenii. “Low-lactobacilli” was defined as an increased diversity of anaerobic or mixture of aerobe and facultative anaerobe bacteria (such as Gardnerella and Prevotella) based on the cut-offs and categorization used in the individual studies.

Results

Primary clinical outcomes were:

• Among women who delivered preterm, the pooled proportion with “low-lactobacilli” was 0.41 (95% CI 0.30-0.53) compared to 0.29 (95% CI 0.20-0.38) of women with full-term deliveries.
• The risk of preterm births was higher among women with “low-lactobacilli” compared to L. crispatus (OR 1.69, 95%CI 1.15 -2.49).”Low-lactobacilli” included Garnerella and Provotella, both of which are known to promote inflammatory cytokines and are commonly found in vaginal microbiome just before preterm premature rupture of membranes (PPROM).

• The diversity of the vaginal microbiome is reported to play an important role in the risk of preterm births.
• Women with low Lactobacilli seem to be at a greater risk of delivering preterm compared to women with L. crispatus dominant microbiome.
• Based on this study, practitioners could therefore consider testing the vaginal microbiome of their patients for low Lactobacilli and/or the dominance of Gardnerella and Prevotella.
• Practitioners may also consider recommending specific probiotic supplementation during pregnancy to increase the dominance of Lactobacilli and L. crispatus vaginal microbiome.

• In the past, researchers have grouped the microbiome into categories based on dominating species, which is not ideal. Therefore, further studies are needed where individual microbiome sequencing data is used to make comparisons.
• Additionally, longitudinal studies are needed with higher sample sizes to investigate the natural changes of the vaginal microbiome during pregnancy and the physiological mechanisms underlying these apparent different risk profiles.
• Furthermore, randomized-controlled trials are needed to establish if pregnant women could benefit from specific probiotic supplementation during pregnancy.