Prevention of recurrent spontaneous preterm delivery using probiotics: results from a prospective, single-arm, multicenter trial

BACKGROUND: The rate of recurrent spontaneous preterm delivery is 30% (95% confidence interval, 27%-34%) globally and 22.3% in Japan. Probiotics containing Clostridium species may reduce spontaneous preterm delivery by inducing regulatory T cells, which play an important role in maintaining pregnancy. OBJECTIVE: We investigated whether the administration of probiotics including Clostridium butyricum prevented recurrent spontaneous preterm delivery in high-risk pregnant women. STUDY DESIGN: We conducted a prospective, single-arm, nonblinded, multicenter trial across 31 hospitals in Japan between May 2021 and October 2024. Pregnant women (aged 18-43 years) with a history of spontaneous preterm delivery received oral probiotics (Clostridium butyricum [10 mg/tablet], Enterococcus faecium [2 mg/tablet], and Bacillus subtilis [10 mg/tablet]) from 10 to 14 weeks to 36 weeks 6 days of gestation. The primary endpoint was the rate of recurrent spontaneous preterm delivery at