Oral supplementation with probiotics containing Clostridium species may protect against the recurrence of spontaneous preterm delivery in high-risk pregnant women, according to a prospective, single-arm, trial conducted in Japan.
Following oral probiotics supplementation from 10–14 weeks through 36 weeks of gestation, the primary endpoint of the rate of recurrent spontaneous preterm delivery at <37 weeks was 14.9 percent among women with a history of spontaneous preterm delivery. [Am J Obstet Gynecol 2026;doi:10.1016/j.ajog.2026.02.027]
“The observed rate of spontaneous preterm delivery at <37 weeks was lower than the rate of 22.3 percent reported in a national database,” corresponding to a 33-percent risk reduction (relative risk, 0.67, 95 percent confidence interval [CI], 0.50–0.87; p=0.0013),” the authors said.
The rate of spontaneous preterm delivery at <34 weeks was 3.5 percent, and the rate of recurrent spontaneous preterm delivery at <24 weeks in the subgroup of women with a history of extreme preterm delivery was 1.5 percent.
There were no cases of neonatal death, periventricular leukomalacia, or necrotizing enterocolitis documented. The median birthweight was 883 g for infants born at ≤28 weeks, 1,836 g for those born at 29–33 weeks, and 2,439 g for those born at 34–36 weeks.
“The safety profile of the probiotic intervention was favourable,” the authors noted.
Adverse events (AEs) occurred in only 8.2 percent of participants and were mostly mild, with iron-deficiency anaemia being the most common. There were no serious AEs related to the study intervention.
“This prospective trial suggests a potential benefit of probiotics containing C butyricum in reducing the rate of recurrent sPTD in high-risk women. The favourable safety profile, ease of administration, and accessibility of probiotics make this approach promising for widespread implementation,” the authors said.
A total of 315 pregnant women (median age 35 years, median BMI 20.6 kg/m2, median number of pregnancies 3) participated in the study. These participants began taking oral probiotics between 10 and 14 weeks of gestation.
The oral probiotic preparation contained Clostridium butyricum (10 mg/tablet), Enterococcus faecium (2 mg/tablet), and Bacillus subtilis (10 mg/tablet) and taken three times daily until late miscarriage, spontaneous preterm delivery, or 36 weeks of gestation in term delivery subjects, with a maximum administration duration of 188 days.
How probiotics work
According to the authors, the potential mechanism underlying the protective effect of probiotics on the risk of recurrent spontaneous preterm delivery involves the induction of regulatory T cells by Clostridium species. Regulatory T cells are essential for maintaining immune tolerance in pregnancy, they pointed out.
“The initiation of probiotics containing C butyricum from early pregnancy may help suppress intra-amniotic inflammation, which may result in a reduction in [the incidence of] early spontaneous preterm delivery,” the authors said.
From a clinical perspective, probiotic supplementation offers several advantages over existing interventions for preventing recurrent spontaneous preterm delivery, they added. “It is noninvasive, relatively inexpensive, and widely available, making it particularly suitable for implementation in various healthcare settings, including resource-limited environments where preterm birth rates are often the highest.”
Compared with vaginal progesterone or cervical cerclage, probiotic administration is simpler and requires minimal healthcare infrastructure, the authors noted. Indeed, in an analysis of medication adherence, 97.5 percent of the study cohort took at least 80 percent of the prescribed probiotic doses.
“If [the study findings are] validated, probiotic supplementation may represent an important addition to the limited arsenal of interventions available to prevent preterm birth, potentially reducing the substantial global burden of prematurity-related morbidity and mortality,” they said.