Probiotic effects on late-onset sepsis in very preterm infants: a randomized controlled trial
BACKGROUND AND OBJECTIVE: Late-onset sepsis frequently complicates prematurity, contributing to morbidity and mortality. Probiotics may reduce mortality and necrotizing enterocolitis (NEC) in preterm infants, with unclear effect on late-onset sepsis. This study aimed to determine the effect of administering a specific combination of probiotics to very preterm infants on culture-proven late-onset sepsis. METHODS: A prospective multicenter, double-blinded, placebo-controlled, randomized trial compared daily administration of a probiotic combination (Bifidobacterium infantis, Streptococcus thermophilus, and Bifidobacterium lactis, containing 1 × 109 total organisms) with placebo (maltodextrin) in infants born before 32 completed weeks' gestation weighing 2011, 1099 very preterm infants from Australia and New Zealand were randomized. Rates of definite late-onset sepsis (16.2%), NEC of Bell stage 2 or more (4.4%), and mortality (5.1%) were low in controls, with high breast milk feeding rates (96.9%). No significant difference in definite late-onset sepsis or all-cause mortality was found, but this probiotic combination reduced NEC of Bell stage 2 or more (2.0% versus 4.4%; relative risk 0.46, 95% confidence interval 0.23 to 0.93, P = .03; number needed to treat 43, 95% confidence interval 23 to 333). CONCLUSIONS: The probiotics B infantis, S thermophilus, and B lactis significantly reduced NEC of Bell stage 2 or more in very preterm infants, but not definite late-onset sepsis or mortality. Treatment with this combination of probiotics appears to be safe.