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

Abstract

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.

Immunonutrition for Preterm Infants

“…Meta-analyses of these trials which have assessed a range of different species and multi-organism combinations suggest that prophylactic probiotics halve the risk of NEC and reduce all-cause mortality by one-third [31, 32]. Most trials and meta-analyses of their data do not show statistically significant effects of probiotics on the risk of late-onset infection.…”

Randomized controlled trial on the impact of early-life intervention with bifidobacteria on the healthy infant fecal microbiota and metabolome

“…Although commercially available formulas are supplemented with bacteria considered as probiotics, little is known about their ability to modulate the infant gut microbial composition and function (5,6). The vast majority of published studies have focused on the use of probiotics in disease-related contexts, including necrotizing enterocolitis in preterm infants, gastrointestinal and respiratory infections, and allergic reactions (7)(8)(9)(10). Their use in healthy cohorts is common, but available data are limited in terms of repeated measurements over time and duration of probiotic administration (11)(12)(13).…”

Probiotics for preterm infants — The story searching for an end

“…Data from systematic reviews of randomized controlled trials (RCTs) and non-RCTs confirm that probiotics significantly reduce the risk of ≥Stage II NEC, all-cause mortality and LOS, and improve feed tolerance in preterm very low birth weight (VLBW) infants [1]. No other intervention in neonatal medicine comes close to probiotics in terms of the effect size for NEC and mortality, and supporting evidence from research and clinical practice [2].…”