Efficacy and acceptability of different probiotic products plus laxatives for pediatric functional constipation: a network meta-analysis of randomized controlled trials.

Study Design

Type: Meta-Analysis
Sample size: n = 710
Population: children with pediatric functional constipation
Methods: frequentist model-based network meta-analysis (NMA) included RCTs of probiotic supplements for functional constipation in children; nine RCTs were included (N = 710; mean age = 5.5 years; 49.4% girls)

The prevalence of pediatric constipation ranges from 0.7 to 29.6% across different countries. Functional constipation accounts for 95% of pediatric constipation, and the efficacy of pharmacotherapy is limited, with a success rate of 60%. Several randomized controlled trials (RCTs) have shown the benefits of probiotic supplements in treating this condition. However, the reported strains of probiotics varied among the RCTs. We aimed to compare the efficacy and acceptability of different probiotic supplements for pediatric functional constipation. The current frequentist model-based network meta-analysis (NMA) included RCTs of probiotic supplements for functional constipation in children. The primary outcome was changes in bowel movement or stool frequency; acceptability outcome was all-cause discontinuation. Nine RCTs were included (N = 710; mean age = 5.5 years; 49.4% girls). Most probiotic products, used either alone or combined with laxatives, were associated with significantly better improvement in bowel movement or stool frequency than placebo/control. Protexin plus laxatives (standardized mean difference (SMD) = 1.87, 95% confidence interval (95% CI) = 0.85 to 2.90) were associated with the greatest improvement in bowel movement or stool frequency among all the investigated probiotic products. For the single probiotic interventions, only Lactobacillus casei rhamnosus Lcr35 was associated with significant efficacy compared to placebo/control treatments (SMD = 1.37, 95% CI: 0.32 to 2.43). All the investigated probiotic products had fecal incontinence and patient drop-out rates similar to those of placebo/control treatments. Conclusion: The results of our NMA support the application of an advanced combination of probiotics and laxatives for pediatric functional constipation if there is no concurrent contraindication. Registration: PROSPERO (CRD42022298724). What is Known: • Despite of the high prevalence of pediatric constipation, which ranges from 0.7% to 29.6%, the efficacy of pharmacotherapy is limited, with a success rate of 60%. Several randomized controlled trials (RCTs) have shown the benefits of probiotic supplements in treating this condition. However, the reported strains of probiotics varied among the RCTs. The widely heterogeneous strains of probiotics let the traditional meta-analysis, which pooled all different strains into one group, be nonsense and insignificant. What is New: • By conducting a comprehensive network meta-analysis, we aimed to compare the efficacy and acceptability of different strains of probiotic supplements for pediatric functional constipation. Network meta-analysis of nine randomized controlled trials revealed that the most probiotic products, used either alone or combined with laxatives, were associated with significantly better improvement in bowel movement or stool frequency than placebo/control. Protexin plus laxatives was associated with the greatest improvement in bowel movement or stool frequency among all the investigated probiotic products. For the single probiotic interventions, only Lactobacillus casei rhamnosus Lcr35 was associated with significant efficacy compared to placebo/control treatments. All the investigated probiotic products had fecal incontinence and patient drop-out rates similar to those of placebo/control treatments.

Research Insights

Supplement	Dose	Health Outcome	Effect Type	Effect Size	Source
Lactobacillus casei PXN 37	—	Improved Bowel Movement Frequency	Beneficial	Moderate	View source Protexin plus laxatives (standardized mean difference (SMD) = 1.87, 95% confidence interval (95% CI) = 0.85 to 2.90) were associated with the greatest improvement in bowel movement or stool frequency among all the investigated probiotic products.
Lactobacillus casei PXN 37	—	No Increase in Fecal Incontinence	Neutral	Small	View source All the investigated probiotic products had fecal incontinence and patient drop-out rates similar to those of placebo/control treatments.
Lactobacillus rhamnosus PXN 54	—	Improved Stool Frequency	Beneficial	Large	View source Protexin plus laxatives (standardized mean difference (SMD) = 1.87, 95% confidence interval (95% CI) = 0.85 to 2.90) were associated with the greatest improvement in bowel movement or stool frequency among all the investigated probiotic products.
Lactobacillus rhamnosus PXN 54	—	Unchanged Treatment Discontinuation	Neutral	Small	View source All the investigated probiotic products had fecal incontinence and patient drop-out rates similar to those of placebo/control treatments.
Streptococcus thermophilus PXN 66	—	Improved Bowel Movement Frequency	Beneficial	Moderate	View source Protexin plus laxatives (standardized mean difference (SMD) = 1.87, 95% confidence interval (95% CI) = 0.85 to 2.90) were associated with the greatest improvement in bowel movement or stool frequency among all the investigated probiotic products.
Streptococcus thermophilus PXN 66	—	Improved Stool Frequency	Beneficial	Large	View source Protexin plus laxatives (standardized mean difference (SMD) = 1.87, 95% confidence interval (95% CI) = 0.85 to 2.90) were associated with the greatest improvement in bowel movement or stool frequency among all the investigated probiotic products.
Streptococcus thermophilus PXN 66	—	No Increase in Fecal Incontinence	Neutral	Small	View source All the investigated probiotic products had fecal incontinence and patient drop-out rates similar to those of placebo/control treatments.
Streptococcus thermophilus PXN 66	—	Reduced Discontinuation Rates	Neutral	Small	View source All the investigated probiotic products had fecal incontinence and patient drop-out rates similar to those of placebo/control treatments.