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Published on: January 27, 2019
Probiotics Reduce Mortality and Morbidity in Preterm, Low-Birth-Weight Infants: A Systematic Review and Network
Rebecca L Morgan1, Geoffrey A Preidis2, Purna C Kashyap3
1Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.
Insights
Multi-strain probiotics, particularly combinations of Lactobacillus and Bifidobacterium species, significantly reduce mortality and necrotizing enterocolitis (NEC) in preterm infants. These combinations also shorten hospital stays and time to full feeding, offering superior benefits over single-strain probiotics.
Area of Science:
- Neonatal Medicine
- Microbiology
- Clinical Nutrition
Background:
- Preterm, low-birth-weight neonates are susceptible to mortality and morbidities like necrotizing enterocolitis (NEC) and sepsis.
- Probiotics are explored as a strategy to improve outcomes in this vulnerable population.
- Evidence comparing single-strain versus multiple-strain probiotic formulations remains unclear.
Purpose of the Study:
- To conduct a network meta-analysis comparing the effectiveness of single-strain and multiple-strain probiotics in preterm neonates.
- To evaluate the impact of different probiotic formulations on key neonatal outcomes.
Main Methods:
- A systematic search of multiple databases (MEDLINE, Embase, etc.) was performed up to January 2019.
- A frequentist network meta-analysis of 63 randomized trials involving 15,712 preterm infants was conducted.
- The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess evidence certainty.
Main Results:
- Combinations of Lactobacillus and Bifidobacterium species demonstrated moderate to high evidence for reducing all-cause mortality (OR, 0.56; 95% CI, 0.39-0.80) compared to placebo.
- Several probiotic combinations, including Lactobacillus and Bifidobacterium spp., significantly reduced severe NEC.
- Specific single-species probiotics (B. animalis subsp lactis, L. reuteri) and certain combinations reduced hospitalization duration.
Conclusions:
- Combinations of Lactobacillus and Bifidobacterium species show superiority over single- and other multiple-strain probiotics for improving outcomes in preterm neonates.
- Certain probiotic combinations may offer the most significant reduction in NEC development.
- Further research is warranted to confirm these findings and optimize probiotic use.
Background & Aims:
We aimed to compare the effectiveness of single- vs multiple-strain probiotics in a network meta-analysis of randomized trials.
Methods:
We searched MEDLINE, Embase, Science Citation Index Expanded, CINAHL, Scopus, Cochrane CENTRAL, BIOSIS Previews, and Google Scholar through January 1, 2019, for studies of single-strain and multistrain probiotic formulations on the outcomes of preterm, low-birth-weight neonates. We used a frequentist approach for network meta-analysis and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence. Primary outcomes included all-cause mortality, severe necrotizing enterocolitis (NEC) (Bell stage II or more), and culture-proven sepsis.
Results:
We analyzed data from 63 trials involving 15,712 preterm infants. Compared with placebo, a combination of 1 or more Lactobacillus species (spp) and 1 or more Bifidobacterium spp was the only intervention with moderate- or high-quality evidence of reduced all-cause mortality (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.39-0.80). Among interventions with moderate- or high-quality evidence for efficacy compared with placebo, combinations of 1 or more Lactobacillus spp and 1 or more Bifidobacterium spp, Bifidobacterium animalis subspecies lactis, Lactobacillus reuteri, or Lactobacillus rhamnosus significantly reduced severe NEC (OR, 0.35 [95% CI, 0.20-0.59]; OR, 0.31 [95% CI, 0.13-0.74]; OR, 0.55 [95% CI, 0.34-0.91]; and OR, 0.44 [95% CI, 0.21-0.90], respectively). There was moderate- or high-quality evidence that combinations of 1 or more Lactobacillus spp and 1 or more Bifidobacterium spp and Saccharomyces boulardii reduced the number of days to reach full feeding (mean reduction of 3.30 days [95% CI, reduction of 5.91-0.69 days]). There was moderate- or high-quality evidence that, compared with placebo, the single-species product B animalis subsp lactis or L reuteri significantly reduced duration of hospitalization (mean reduction of 13.00 days [95% CI, reduction of 22.71-3.29 days] and mean reduction of 7.89 days [95% CI, reduction of 11.60-4.17 days], respectively).
Conclusions:
In a systematic review and network meta-analysis of studies to determine the effects of single-strain and multistrain probiotic formulations on outcomes of preterm, low-birth-weight neonates, we found moderate to high evidence for the superiority of combinations of 1 or more Lactobacillus spp and 1 or more Bifidobacterium spp vs single- and other multiple-strain probiotic treatments. The combinations of Bacillus spp and Enterococcus spp, and 1 or more Bifidobacterium spp and Streptococcus salivarius subsp thermophilus, might produce the largest reduction in NEC development. Further trials are needed.
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