Probiotic effects on late-onset sepsis in very preterm infants: a randomized controlled trial

Pediatrics. 2013 Dec;132(6):1055-62. doi: 10.1542/peds.2013-1339. Epub 2013 Nov 18.


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 × 10(9) total organisms) with placebo (maltodextrin) in infants born before 32 completed weeks' gestation weighing <1500 g. The primary outcome was at least 1 episode of definite late-onset sepsis.

Results: Between October 2007 and November 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.

Keywords: infant; necrotizing enterocolitis; preterm; probiotics; sepsis.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bifidobacterium
  • Double-Blind Method
  • Enterocolitis, Necrotizing / mortality
  • Enterocolitis, Necrotizing / prevention & control
  • Female
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Infant, Premature, Diseases / mortality
  • Infant, Premature, Diseases / prevention & control*
  • Intention to Treat Analysis
  • Logistic Models
  • Male
  • Probiotics / therapeutic use*
  • Prospective Studies
  • Sepsis / mortality
  • Sepsis / prevention & control*
  • Streptococcus thermophilus
  • Treatment Outcome