Probiotics in critically ill children: a systematic review and meta-analysis of randomized controlled trials

To determine the efficacy of probiotics/synbiotics among critically ill children. In this meta-analysis, randomized controlled trials (RCTs) comparing probiotics/synbiotics with placebo/control among critically ill children from inception to 31st March 2025 were included by searching PubMed, Embase, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and WHO International Clinical Trials Registry Platform. RevMan version 5.4 was used for data analysis. Data was pooled regarding mortality (primary outcome); and rates of healthcare associated infections (HCAIs), ventilator-associated pneumonia (VAP) or healthcare-associated pneumonia (HAP), and diarrhea; and duration of mechanical ventilation, pediatric intensive care unit (PICU), hospital stay, and adverse events due to administration of probiotics (secondary outcomes). Quality of trials was assessed by Cochrane risk-of-bias tool. The Certainty of Evidence (CoE) was assessed by GRADEpro GDT. Twelve RCTs with 1051 critically ill children were included. Probiotic and control groups had similar mortality (11% vs. 13.4%, RR: 0.81, 95%CI: 0.59–1.12, p = 0.20), rates of HCAIs (10.2% each, RR: 1.04, 95%CI: 0.39–2.75, p = 0.94), diarrhea (16.7% vs. 19.6%, RR: 0.73, 95%CI: 0.32–1.66, p = 0.46), and duration of mechanical ventilation [mean difference (MD): -1.65, 95%CI: -3.43 to 0.14, p = 0.07). Probiotic group had significantly lower rates of VAP or HAP (11.9% vs. 25.4%, RR: 0.48, 95%CI: 0.30–0.77, p = 0.002), shorter duration of PICU stay (MD: -1.94, 95%CI: -3.15 to -0.72, p = 0.002), and hospital stay (MD: -5.98, 95%CI: -9.30 to -2.66, p = 0.0004). No adverse events were reported with administration of probiotics per se. Majority of the RCTs had low risk of bias. Among critically ill children, probiotic administration was associated with no impact on mortality (moderate CoE); significantly lower rates of VAP or HAP (low CoE), and shorter duration of PICU (moderate CoE) and hospital stay (low CoE); and similar HCAIs, diarrhea, or duration of mechanical ventilation (very low CoE). However, the benefits on VAP/HAP and length of stay require confirmation in larger RCTs. (CRD42024577154, 18/8/2024).