Probiotics for the prevention of surgical necrotizing enterocolitis: systematic review and meta-analysis

Aim of the Study Probiotic administration to preterm infants has the potential to prevent necrotizing enterocolitis (NEC). Data from randomized controlled trials (RCTs) are conflicting but metaanalyses seem to support this intervention. To date, these analyses have not focussed on surgical NEC. We aimed to determine the effect of probiotic administration to preterm infants on prevention of surgical NEC. Methods A systematic review of RCTs of probiotic administration to preterm infants was performed. Studies were included if RCT outcomes included any of (i) Bell’s Stage 3 NEC; (ii) surgery for NEC; (iii) deaths attributable to NEC. Article selection and data extraction was performed independently by two authors; conflicts were adjudicated by a third author. Data were metaanalysed using Review Manager 5.3. A random effects model was decided on a priori because of the heterogeneity of study design; data are risk ratio (RR) with 95% CI. Main Results Thirty-eight RCTs reported NEC as an outcome. Data on surgical NEC could be extracted from 19 RCTs, all of which were included. A variety of probiotic products was administered across studies. Description of surgical NEC in most studies was poor. Only 6/19 specifically reported incidence of surgery for NEC, 12/19 Bell’s stage 3 and 13/19 NEC-associated mortality. Although there was a trend towards probiotic administration reducing stage 3 NEC, this was not significant (RR 0.74 [0.52-1.05], p=0.09). There was no effect of probiotics on the RR of surgery for NEC (RR 0.84 [0.56-1.25], p=0.38). Probiotics did, however, reduce the risk of NEC-associated mortality (RR 0.56 [0.34-0.93], p=0.03) Conclusion Despite 38 RCTs on probiotic prevention of NEC, evidence for prevention of surgical NEC is not strong, partly due to poor reporting. In studies included in this meta-analysis, probiotic administration was associated with a reduction in NEC related mortality. Key messages - The evidence that probiotic administration is associated with a decreased incidence of surgical NEC is limited - This is mainly due to poor reporting of surgical NEC in randomized controlled trials and we urge better reporting of surgical aspects of NEC in future trials What is known about the subject In various RCTs and meta-analyses, it has been suggested that probiotic administration is associated with a decrease in incidence of definite NEC. What this study adds The reporting of surgical aspects of NEC in RCTs of probiotic administration is poor. The evidence that probiotic administration is associated with a decrease in incidence of surgical NEC, or surgery for NEC, is limited. Probiotic administration is associated with a decrease in NEC-associated mortality.