The "Golden Age" of Probiotics: A Systematic Review and Meta-Analysis of Randomized and Observational Studies in Preterm Infants

Neonatology. 2017;112(1):9-23. doi: 10.1159/000454668. Epub 2017 Feb 15.


Background: Over the last few years, probiotics have been one of the most studied interventions in neonatal medicine.

Objectives: The aim of this work was to analyse all studies (randomized controlled trials, RCTs, and observational studies) assessing the use of probiotics in very low birth weight (VLBW) preterm infants.

Search methods: A systematic literature search was conducted using PubMed, Embase, Cochrane Library, and Web of Science. The data from RCTs and observational studies were pooled and analysed separately.

Selection criteria: RCTs and observational studies that enrolled VLBW infants with enteral administration of probiotics were considered. Extracted study data included probiotic characteristics and at least 1 clinical outcome (necrotizing enterocolitis [NEC], late-onset sepsis or all-cause mortality).

Data collection and analysis: Forty-four studies were eligible for our review: 30 RCTs and 14 observational studies. Severe NEC rates (stage II or more) and all-cause mortality were reduced among the probiotic groups in both the RCTs (RR 0.57, 95% CI 0.47-0.70, and RR 0.77, 95% CI 0.65-0.92, respectively) and the observational studies (RR 0.51, 95% CI 0.37-0.70, and RR 0.71, 95% CI 0.62-0.81, respectively). Furthermore, there was a 12% reduction in the risk of sepsis in RCTs and a 19% reduction in observational studies. The meta-analysis of observational studies showed a reduction in the risk of NEC in extremely low birth weight infants. However, this was not statistically significant.

Conclusions: This meta-analysis of RCT and observational studies found that the use of probiotics was beneficial for the prevention of severe NEC, late-onset sepsis, and all-cause mortality in VLBW infants.

Keywords: Mortality; Necrotizing enterocolitis; Preterm; Probiotics; Sepsis; Very low birth weight infants.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Birth Weight
  • Chi-Square Distribution
  • Enterocolitis, Necrotizing / microbiology
  • Enterocolitis, Necrotizing / mortality
  • Enterocolitis, Necrotizing / prevention & control*
  • Gastrointestinal Microbiome*
  • Gastrointestinal Tract / microbiology*
  • Gestational Age
  • Humans
  • Infant, Low Birth Weight
  • Infant, Newborn
  • Infant, Premature*
  • Observational Studies as Topic
  • Odds Ratio
  • Premature Birth*
  • Probiotics / adverse effects
  • Probiotics / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Risk Factors
  • Sepsis / microbiology
  • Sepsis / mortality
  • Sepsis / prevention & control*
  • Treatment Outcome