AYMEN ALI ALQURAIN, MALEK ANAS LABIB MOHAMMED, WAHIBA ABDELRAHMAN MOHAMMED A HAMZA, YOUCEF BELAIDI, OLA LUTFI FATANI, LUGAIN AYMAN SAMMAN, AHMED ALI KHIDIR MUSTAFA, SARRA ELNOUR AHMED ELNOUR
DOI: https://doi.org/Background: As necrotizing enterocolitis (NEC) remains a leading cause of morbidity and mortality in preterm infants. Prophylactic administration of probiotics has been proposed to modulate the gut microbiome and reduce NEC risk. Although uncertainty persists regarding the efficacy and safety of this intervention, particularly concerning sepsis and mortality, this article aimed to review the evidence and quantify the efficacy and safety of probiotics for preventing NEC, culture-proven sepsis, and all-cause mortality in this vulnerable population.
Methods: This systematic review and meta-analysis was conducted in accordance with PRISMA guidelines and prospectively registered in PROSPERO as a comprehensive search was conducted to identify randomized controlled trials (RCTs) comparing any prophylactic probiotic intervention to a placebo or no treatment in preterm infants (<37 weeks gestation). The primary outcome being NEC (Bell stage ≥II), while secondary outcomes of culture-proven sepsis and all-cause mortality. Data were pooled using a random-effects model with results presented as odds ratios (ORs) and 95% confidence intervals (CIs).
Results: A total of 21 RCTs involving 10,951 infants were included, from which a meta-analysis of 19 studies with 7,587 infants showed that probiotic supplementation was associated with a significant reduction in the incidence of NEC (OR = 0.55, 95% CI 0.47–0.65; I²=0.0%). A significant reduction in all-cause mortality was also observed across 18 studies (n = 7,452) (OR = 0.76, 95% CI 0.67–0.86; I²=37.7%). The effect on culture-proven sepsis across 19 studies with 7,316 infants showed a protective trend but did not reach conventional statistical significance (OR = 0.79, 95% CI 0.66–0.95; p = 0.0541; I² = 37.7%), while subgroup analyses suggested that mixed-genera probiotic formulations conferred the greatest benefit against NEC.
Conclusion: The prophylactic administration of probiotics significantly reduces the incidence of severe NEC and all-cause mortality in preterm infants which support the use of well-studied, quality-controlled probiotic formulations as a standard preventative strategy in this high-risk population. Although the choice of specific probiotic strains and the need for further research to clarify their effect on sepsis remain important considerations.
