Effect and Safety of Saccharomyces boulardii for Neonatal Necrotizing Enterocolitis in Pre-term Infants: A Systematic Review and Meta-Analysis

Background and Objective: Necrotizing enterocolitis (NEC) is one of the most common and urgent neonatal emergencies in the neonatal intensive care unit. This disease leads to considerable morbidity and mortality; it also imposes a huge financial burden on patient family and society. Thus, Treatment and prevention of NEC are crucial. This meta-analysis aims to investigate the effect and safety of Saccharomyces boulardii for NEC in pre-term infants. Methods: A comprehensive search was retrieved in six major databases. The search included randomized controlled trials (RCTs) reporting the incidence of NEC (stage >= II), sepsis, mortality, feeding intolerance, full feeding days, time to regain birth weight, days of hospitalization and adverse effects. The random model was used to calculate risk ratio (RR), the standard mean difference (SMD) and its 95% confidence interval (95% CI) between the S. boulardii group and control group. Statistical analyses were conducted using Cochrane systematic review software, Rev Man (version 5.3). Results: In total, 10 RCTs involving 1264 participants met the inclusion criteria. There were significant reductions in the incidence of NEC [RR = 0.56, 95% CI (0.36-0.89)], feeding intolerance [RR = 0.52, 95% CI (0.39-0.68)], full feeding days [SMD = -1.25, 95% CI (-2.06 to -0.45)] and hospitalization days [SMD = -1.33, 95% CI (-2.64 to -0.02)] in the study group compared with the control group. However, there were no significant differences in sepsis [RR = 0.84, 95% CI (0.61-1.17)], death [RR = 1.12, 95% CI (0.46-2.70)] and the time to regain birth weight [SMD = -0.93, 95% CI (-1.88 to 0.03)] between the two groups. The adverse effect of S. boulardii was not reported. The overall methodological quality was evaluated as moderate by the Cochrane Bias Risk Assessment Tool. Conclusion: According to this evidence we recommend S. boulardii to prevent NEC, reduce the feeding intolerance, shorten the full feeding days and hospitalization days. However, S. boulardii might be invalid on the incidence of sepsis, mortality and the time to regain birth weight.