Effects of oral probiotic supplements on vaginal microbiota during pregnancy: a randomised, double‐blind, placebo‐controlled trial with microbiome analysis

Design: randomized, double-blind, placebo-controlled trial conducted at four UK maternity units. Participants: pregnant women aged 16+ at 9–14 weeks’ gestation; 304 randomised (152 per group); 238 included in primary analysis (115 placebo, 123 probiotic). Vaginal swabs collected at baseline, 18–20 weeks, and 34–36 weeks for microbiome analysis; primary outcome: rate of bacterial vaginosis (BV; Nugent score ≥7) at 18–20 weeks.

One capsule daily containing Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14, each at 2.5e9 CFU, from recruitment (9–14 weeks’ gestation) until delivery.

Probiotic supplementation did not modify vaginal microbiota or reduce BV at 18–20 weeks. BV rates: 15% in probiotic vs 9% in placebo (adjusted OR 1.82, 95% CI 0.64–5.19; P=0.26). L. rhamnosus GR-1 colonised in 5% of participants in both groups; L. reuteri RC-14 not detected. Alpha and beta diversity of vaginal microbiota did not differ between groups at 9–14 or 18–20 weeks. Conclusion: this probiotic regimen from early pregnancy did not alter vaginal microbiota or BV risk; further work is needed to identify strains that can colonize and modulate vaginal microbiota and potentially influence pregnancy outcomes such as preterm birth.

Underpowered due to lower-than-expected BV event rate and recruitment shortfall; only 304 women randomised (238 in primary analysis); high screen-to-enrol rejection (~23% enrolled); substantial loss to follow-up and incomplete data; adherence assessed by self-report; minimal vaginal colonization by RC-14 and limited GR-1 colonization; baseline Nugent scores differed between groups; limited generalizability beyond four UK maternity units.