Evidence increasing that probiotics reduce incidence of necrotizing enterocolitis in very low birth weight infants
Article Outline
- Question
- Design
- Data Sources
- Study Selection and Assessment
- Outcomes
- Main Results
- Conclusions
- Commentary
- References
- Copyright
Deshpande G, Rao S, Patole S, Bulsara M. Updated meta-analysis of probiotics for preventing necrotizing enterocolitis in preterm neonates. Pediatrics. 2010;125:921-30.
Question
Among preterm (<34 weeks' gestation) very low birth weight (birth weight <1500 g) neonates, does probiotic supplementation prevent necrotizing enterocolitis (NEC)?
Design
Systematic review with meta-analysis.
Data Sources
Cochrane Central register; MEDLINE, Embase, and CINAHL databases; and conference proceedings. Cochrane Neonatal Review Group search strategy was followed.
Study Selection and Assessment
Randomized controlled trials of any enteral probiotic supplementation that started within the first 10 days and continued for ≥7 days in preterm very low birth weight neonates and reported on stage 2 NEC or higher (Modified Bell Staging).
Outcomes
Primary outcomes were efficacy of probiotic supplement in preventing stage 2 NEC or higher, safety in terms of blood culture–positive sepsis including that by the organism(s) in the probiotic supplement, and any other adverse events reported by the authors. Secondary outcomes included time to full feeds and duration of hospital stay.
Main Results
A total of 11 (N = 2176), including 4 new (n = 783), trials were eligible for inclusion in the meta-analysis by using a fixed-effects model. Risk for NEC and death was significantly lower. Risk for sepsis did not differ significantly. No significant adverse effects were reported. Trial sequential analysis showed 30% reduction in the incidence of NEC (α = .05 and .01; power: 80%).
Conclusions
The results suggest significant benefits of probiotic supplements in reducing death and disease in preterm neonates.
Commentary
Deshpande et al present results from an updated meta-analysis on the effect of probiotic supplementation for preventing NEC. The authors conclude that “probiotics should now be offered as a routine therapy for preterm neonates” and “additional placebo-controlled trials on this topic are not warranted.” In this analysis, results from 11 studies published from 1997 to 2009 are merged together; however, the 11 different studies evaluated 11 different interventions. Each study had a unique combination of probiotic strain(s), dosage, matrix, and duration of therapy. Although pooling of different interventions in a meta-analysis is reasonable, this technique should be reserved only when all the treatments fall into the same therapeutic class. For example, in the treatment of persistent asthma, therapies such as inhaled corticosteroids, leukotriene modifiers, and long-acting beta-agonists in combination with inhaled corticosteroids have all been shown to be effective in preventing exacerbations. However, one would not combine these different therapies for meta-analysis to determine the effect of “a daily asthma medication” on preventing asthma exacerbations. Probiotic supplements are not homogenous. Individual probiotic strains may be effective via different mechanisms, such as increasing gut barrier function to prevent translocation, direct competition with pathologic bacteria, and immune modulation, etc.1 One of the 11 studies even used a yeast product, Saccharomyces boulardii, which may exert its effect through neutralization of bacterial toxins, among others.2 Current research in defining the infant gut microbiota, metagenome, and metabolome may one day allow investigators to identify which individual, separate mechanisms, (or single, shared mechanism) may be mediating these effects.3 Due to the heterogeneity of these therapies, it is not clear if these different interventions can be combined to conclusively determine their individual effectiveness, let alone halt all placebo-controlled trials in this area. Finally, by combining studies featuring different regimens, this meta-analysis leads to results that are difficult to apply in practice. In the end, a clinician will need to select a specific strain(s), dose, matrix, and duration of therapy. Although much has been accomplished already, further research is needed to assess the effectiveness of specific probiotic strains for NEC.
References
- . Mechanisms of probiotic actions–a review. International Journal of Medical Microbiology. 2010;300:57–62
- Enteral feeding of premature neonates with Saccharomyces boulardii. Early Hum Dev. 2003;74:89–96
- . Redefining the role of intestinal microbes in the pathogenesis of necrotizing enterocolitis. Pediatrics. 2010;125:777–785
PII: S0022-3476(10)00783-3
doi:10.1016/j.jpeds.2010.09.023
© 2010 Mosby, Inc. All rights reserved.
