Prophylactic Probiotics for Preterm Infants: A Systematic Review and Meta-Analysis of Observational Studies

Neonatology. 2016;109(2):105-12. doi: 10.1159/000441274. Epub 2015 Dec 2.

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.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Enterocolitis, Necrotizing / mortality
  • Enterocolitis, Necrotizing / prevention & control*
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Infant, Premature, Diseases / mortality
  • Infant, Premature, Diseases / prevention & control*
  • Observational Studies as Topic
  • Probiotics / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Sepsis / mortality
  • Sepsis / prevention & control