Heterogeneous Response Patterns to Multispecies Probiotics in Patients With Constipation During Pregnancy: An Exploratory Analysis of a Phase 2 Clinical Trial.

Abstract

Objectives: This study aimed to evaluate the efficacy and safety of multispecies probiotics in patients with constipation during pregnancy.

Methods: This Phase 2, randomized, double-blind, placebo-controlled trial was conducted across 10 hospitals in China. One hundred and twenty-two pregnant females with constipation were randomly assigned in a 2:1 ratio to receive either multispecies probiotics or placebo for 8 weeks. The primary efficacy endpoint was the proportion of patients who achieved a mean CSBM frequency of ≥ 3 per week across the entire 8-week treatment period, together with an increase of ≥ 1 CSBM per week from the baseline weekly average.

Results: The overall response rate did not differ significantly between probiotics (22.78%) and placebo groups (20.51%) (p = 0.779). Weekly response rates showed different temporal patterns between groups (P for interaction = 0.024); however, this did not result in a significant between-group difference at Week 8. In post hoc exploratory subgroup analyses, for patients with baseline SBM < 3/week, baseline straining score ≤ 2, baseline stool consistency score ≤ 2 (Type 1 or 2), and gestational weeks > 20 weeks, the weekly response rate in probiotics increased faster during the treatment period. The probiotic treatment was well tolerated, with no serious adverse events observed.

Conclusions: Multispecies probiotics were safe and well tolerated during pregnancy but did not significantly improve the prespecified primary endpoint within an 8-week treatment period. Post hoc subgroup analyses suggested potentially heterogeneous response trajectories according to baseline bowel frequency, straining severity, stool consistency, and gestational age; however, these findings should be interpreted with caution.