Abstract

OBJECTIVES
Late-onset sepsis (LOS), occurring after 72 hours of birth, is a significant cause of morbidity and mortality especially in preterm neonates. Probiotics have been proposed as a preventive strategy to enhance gut health, modulate immune responses, and reduce the incidence of neonatal sepsis. We aimed to evaluate the effectiveness of probiotics in preventing neonatal sepsis in preterm neonates, with particular attention to the impact of different strains and dosage regimens.
Methods
Eligible studies included preterm neonates (≤36 weeks gestational age) with culture-proven LOS and focused on probiotic supplementation. Comprehensive searches were conducted in MEDLINE via PubMed, Cochrane CENTRAL, Scopus, and ProQuest up to July 28, 2024. The Revised Cochrane Risk of Bias Tool (RoB 2.0) was applied to assess study quality, and a random-effects meta-analysis was performed using Review Manager (RevMan) version 5.4. Additionally, the certainty of the body of evidence was evaluated using the GRADE approach (Grading of Recommendations Assessment, Development, and Evaluation).
RESULTS
Thirty-one studies including 8,040 preterm neonates were reviewed. Meta-analysis demonstrated that probiotics significantly reduced the incidence of LOS (pooled risk ratio [RR], 0.83; 95% CI, 0.72–0.95). Greater efficacy was observed with multistrain formulations (RR, 0.76; 95% CI, 0.72–0.95) and low-dose regimens (RR, 0.72; 95% CI, 0.56–0.91). Probiotic supplementation was also associated with shorter hospital stays and a trend toward lower mortality, although the latter did not reach statistical significance.
CONCLUSIONS
To effectively reduce LOS in preterm neonates, specific combinations of multistrain probiotics and optimized dosing strategies may provide the most benefit.

• Keywords: Late onset sepsis; Premature infants; Infection prevention; Microbiome therapy; Probiotics supplementation