title: Probiotic effects on late-onset sepsis in very preterm infants: a randomized controlled trial.
abstract: 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.
authors.affiliation: Women's Centre for Infectious Diseases, Bio 21 Institute, 30 Flemington Rd, Parkville 3052, Victoria, Australia. suzanne.garland@thewomens.org.au.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Jacobs
authors.forename: Jacinta M
authors.initials: JM
authors.lastname: Tobin
authors.forename: Gillian F
authors.initials: GF
authors.lastname: Opie
authors.forename: Susan
authors.initials: S
authors.lastname: Donath
authors.forename: Sepehr N
authors.initials: SN
authors.lastname: Tabrizi
authors.forename: Marie
authors.initials: M
authors.lastname: Pirotta
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Morley
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Garland
mesh_terms: D001644:Bifidobacterium; D004311:Double-Blind Method; D020345:Enterocolitis, Necrotizing / Q000401:mortality / Q000517:prevention & control; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000401:mortality / Q000517:prevention & control*; D057194:Intention to Treat Analysis; D016015:Logistic Models; D008297:Male; D019936:Probiotics / Q000627:therapeutic use*; D011446:Prospective Studies; D018805:Sepsis / Q000401:mortality / Q000517:prevention & control*; D048249:Streptococcus thermophilus; D016896:Treatment Outcome
keywords: infant; necrotizing enterocolitis; preterm; probiotics; sepsis