title: Prophylactic Probiotics for Preterm Infants: A Systematic Review and Meta-Analysis of Observational Studies.
abstract: BACKGROUND
  Necrotizing enterocolitis (NEC) is a major morbidity and cause of mortality in preterm neonates. Probiotics seem to have a beneficial role in preventing NEC, which is confirmed in meta-analyses of randomized controlled trials (RCTs). We therefore aimed to review and confirm the efficacy of probiotics in preterm neonates obtained in observational studies.
  
  
  OBJECTIVE
  To assess the effects of prophylactic probiotics in preterm infants.
  
  
  METHODS
  A meta-analysis was performed searching PubMed, EMBASE, CENTRAL (the Cochrane Library) and www.clinicaltrials.gov. Reference lists of reviews of RCTs were also searched. Included studies were observational studies that enrolled preterm infants <37 weeks of gestational age. Trials were included if they administered any probiotics and measured at least one clinical outcome (e.g. NEC, all-cause mortality, sepsis or long-term development scores). Two authors extracted characteristics and outcomes from included studies. The Newcastle-Ottawa Scale was used for quality assessment. A random-effects meta-analysis model was used, and heterogeneity was assessed by the I2 test.
  
  
  RESULTS
  We included 12 studies with 10,800 premature neonates (5,144 receiving prophylactic probiotics and 5,656 controls). The meta-analysis showed a significantly decreased incidence of NEC (risk ratio, RR = 0.55, 95% confidence interval, 95% CI, 0.39-0.78; p = 0.0006) and mortality (RR = 0.72, 95% CI, 0.61-0.85; p < 0.0001). Sepsis did not differ significantly between the two groups (RR = 0.86, 95% CI, 0.74-1.00; p = 0.05).
  
  
  CONCLUSIONS
  Probiotic supplementation reduces the risk of NEC and mortality in preterm infants. The effect sizes are similar to findings in meta-analyses of RCTs. However, the optimal strain, dose and timing need further investigation.
authors.affiliation: Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Rie
authors.initials: R
authors.lastname: Olsen
authors.forename: Gorm
authors.initials: G
authors.lastname: Greisen
authors.forename: Morten
authors.initials: M
authors.lastname: Schrøder
authors.forename: Jesper
authors.initials: J
authors.lastname: Brok
mesh_terms: D020345:Enterocolitis, Necrotizing / Q000401:mortality / Q000517:prevention & control*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000401:mortality / Q000517:prevention & control*; D064887:Observational Studies as Topic; D019936:Probiotics / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D018805:Sepsis / Q000401:mortality / Q000517:prevention & control