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  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.