Effects of Probiotics in Preterm Infants: A Network Meta-analysis

Pediatrics. 2021 Jan;147(1):e20200706. doi: 10.1542/peds.2020-0706. Epub 2020 Dec 15.


Context: Probiotics have proven to be effective in promoting premature infants' health, but the optimal usage is unknown.

Objective: To compare probiotic supplements for premature infants.

Data sources: We searched PubMed, Embase, Cochrane, and ProQuest from inception of these databases to June 1, 2020.

Study selection: Randomized trials of probiotic supplement intervention for preterm infants were screened by 2 reviewers independently. The primary outcomes were mortality and the morbidity of necrotizing enterocolitis (NEC). Secondary outcomes were morbidity of sepsis, time to achieve full enteral feeding, and length of hospital stay.

Data extraction: The data of primary and secondary outcomes were extracted by 2 reviewers and pooled with a random-effects model.

Results: The meta-analysis included 45 trials with 12 320 participants. Bifidobacterium plus Lactobacillus was associated with lower rates of mortality (risk ratio 0.56; 95% credible interval 0.34-0.84) and NEC morbidity (0.47; 0.27-0.79) in comparison to the placebo; Lactobacillus plus prebiotic was associated with lower rates of NEC morbidity (0.06; 0.01-0.41) in comparison to the placebo; Bifidobacterium plus prebiotic had the highest probability of having the lowest rate of mortality (surface under the cumulative ranking curve 83.94%); and Lactobacillus plus prebiotic had the highest probability of having the lowest rate of NEC (surface under the cumulative ranking curve 95.62%).

Limitations: In few studies did authors report the data of infants with a lower birth weight or gestational age.

Conclusions: The efficacy of single probiotic supplements is limited, compared to combined use of probiotics. To achieve optimal effect on premature infant health, combined use of prebiotic and probiotic, especially Lactobacillus or Bifidobacterium, is recommended.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Enteral Nutrition
  • Enterocolitis, Necrotizing / complications
  • Enterocolitis, Necrotizing / mortality
  • Humans
  • Infant, Newborn
  • Infant, Premature*
  • Length of Stay
  • Prebiotics / administration & dosage
  • Probiotics / therapeutic use*
  • Sepsis / complications


  • Prebiotics