Probiotics for the prevention of mortality and sepsis in preterm very low birth weight neonates from low- and middle-income countries: a Bayesian network meta-analysis

Background: Probiotics have been shown to reduce the risk of mortality and necrotizing enterocolitis (NEC) in very low birth weight (VLBW) neonates. The probiotic species with the maximal benefits in neonates from low- and middle-income countries are unknown. Objective: To identify the strain of probiotics with the maximum benefit in preventing neonatal mortality, sepsis, and NEC using the Bayesian network meta-analysis. Search methods: We searched Medline via PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL). We also hand-searched reference lists of previous systematic reviews to identify eligible studies. Selection criteria: Randomized controlled trials (RCTs) from LMICs comparing enteral supplementation of one or more probiotics with another probiotic species or placebo were included. Data collection and analysis: Two authors screened the studies, extracted the data, and examined the risk of bias using the Cochrane risk of bias 2 (RoB 2) tools. Bayesian networkmeta-analysis was performed using the BUGSnet package in R and RStudio (version 1.4.1103). The confidence in the findings was assessed using the Confidence in Network Meta-analysis (CINeMA) web application. Results: Twenty-nine RCTs enrolling 4,906 neonates and evaluating 24 probiotics were included. Only 11 (38%) studies had a low risk of bias. All the studies compared the probiotics with a placebo; none had a head-to-head comparison of different probiotic species. Also, only one study each had evaluated most probiotic regimens. When compared to placebo, the combination of B longum, B bifidum, B infantis, and L acidophilusmay reduce the risk of mortality (relative risk [RR] 0.26; 95% credible interval [CrI] 0.07 to 0.72), sepsis (RR 0.47; 95% CrI 0.25 to 0.83), and NEC (RR 0.31; 95% CrI 0.10 to 0.78) but the evidence is very uncertain. There is low certainty evidence that the single probiotic species, B lactis, could reduce the risk of mortality (RR 0.21; 0.05 to 0.66) and NEC (RR 0.09; 0.01 to 0.32). Conclusion: Given the low to very low certainty of evidence for the efficacy of the two probiotics found to reduce mortality and necrotizing enterocolitis, no firm conclusions can be made on the optimal probiotics for use in preterm neonates in low- and middle-income countries.

Automated summary

In this study, Bayesian network meta-analysis was used to identify the probiotic strain with the maximum benefit in preventing neonatal mortality, sepsis, and NEC. The combination of B longum, B bifidum, B infantis, and L acidophilus may reduce the risk of mortality, sepsis, and NEC, but the evidence is uncertain. B lactis may also reduce the risk of mortality and NEC, but the evidence is uncertain. Further research is needed to determine the optimal probiotics for use in preterm neonates in low- and middle-income countries.