Critical systematic review of the level of evidence for routine use of probiotics for reduction of mortality and prevention of necrotizing enterocolitis and sepsis in preterm infants.

Background & Aims: Probiotics have been suggested to prevent severe necrotizing enterocolitis (NEC) and decrease mortality in preterm infants. The aim of this paper was to systematically analyze the level of evidence (LoE) of published controlled randomized trials (RCTs) on probiotics in preterm infants.

Methods: Literature searches were made up to November 2010. LoE of recommendations based on single trials or meta-analyses were scored following the Oxford Center for Evidence based Medicine approach (1a - meta-analyses of 1b LoE studies; 1b - well designed RCT; 2a - meta-analyses which include 2b LoE studies; 2b - lesser quality RCT).

Results: Fifteen trials were included (Two 1b LoE trials and thirteen 2b LoE trials). Methodological assessment revealed considerable heterogeneity. Some probiotics may be beneficial in relation to reduction of severe NEC (2b LoE) and reduction of mortality (2b LoE). Probiotics do not accelerate feeding advancement (1b and 2b LoE). There was no convincing benefit with regard to prevention of sepsis (1b and 2b LoE).

Conclusion: There is insufficient evidence to recommend routine probiotics. However, there is encouraging data (2b LoE) which justifies the further investigation regarding the efficacy and safety of specific probiotics in circumstances of high local incidence of severe NEC.