A retrospective cohort study by Canadian researchers has found that probiotic supplementation in preterm infants is associated with a significant reduction in all-cause mortality, although not with a lower risk of necrotizing enterocolitis (NEC) or late-onset sepsis.
The study reviewed medical records of 32,667 neonates born at <34 weeks’ gestation between 2016 and 2022 across tertiary-level NICUs in Canada. Of these, 18,793 (57.5%) received probiotics, while 13,874 (42.5%) did not. Infants in the probiotic group had a lower median gestational age (29 vs. 31 weeks) and a higher proportion with birth weights <1,000 g (26.3% vs. 17.7%).
Probiotic regimens varied across centers: 30 NICUs used a multi-strain probiotic containing four Bifidobacterium strains and Lactobacillus rhamnosus, while two used a single-strain product (Lactobacillus reuteri). In the multivariate analyses, the risk of mortality was significantly lower in neonates receiving probiotics than in those who did not.
However, the use of probiotics was not associated with a significant change in the risk of NEC (aOR, 0.92; 95% CI, 0.78, 1.09) or late-onset sepsis (aOR, 0.90; 95% CI, 0.80, 1.01).
The results were similar among infants with birth weights <1,000 g; the risk of all-cause mortality was lower in those who received probiotics than in those that did not (aOR, 0.58; 95% CI, 0.47, 0.71), but there were no significant differences between cohorts in the risk of NEC (aOR, 0.90; 95% CI, 0.71, 1.13) or late-onset sepsis (aOR, 1.01; 95% CI, 0.86, 1.18).
Safety and Probiotic Sepsis
There were 27 documented cases of probiotic sepsis—all in infants who received probiotics—including 20 in those with birth weights <1,000 g. Two deaths were attributed to probiotic sepsis. Despite these rare adverse events, overall mortality benefits outweighed the risks.
Conclusion
Probiotic supplementation in preterm infants, particularly those with very low birth weight, is associated with a significantly reduced risk of all-cause mortality. While the study found no significant effects on NEC or late-onset sepsis, probiotic sepsis remained rare. These findings support the careful use of probiotics in neonatal intensive care, with ongoing monitoring for safety.
The World Health Organization (WHO) defines probiotics as “live microorganisms which, when administered in adequate amounts, confer a health benefit on the host.” This definition underscores that probiotics must be viable to be effective.
Note: Dr. Doolittle disclosed no relevant financial relationships. This commentary does not involve discussion of unapproved or investigational uses of commercial products.