Article Text

Download PDFPDF

Probiotics for the prevention of surgical necrotising enterocolitis: systematic review and meta-analysis
  1. Clare M Rees1,
  2. Nigel J Hall2,
  3. Paul Fleming3,
  4. Simon Eaton1
  1. 1 UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust, London, UK
  2. 2 Department of Paediatric Surgery and Urology, Faculty of Medicine, University of Southampton, Southampton, UK
  3. 3 London School of Medicine and Dentistry, Homerton University Hospital and Barts, London, UK
  1. Correspondence to Dr Simon Eaton; s.eaton{at}


Aim of the study Probiotic administration to preterm infants has the potential to prevent necrotising enterocolitis (NEC). Data from randomised controlled trials (RCT) are conflicting but meta-analyses seem to support this intervention. To date, these analyses have not focused 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 (1) Bell’s stage 3 NEC; (2) surgery for NEC; and (3) deaths attributable to NEC. Article selection and data extraction were performed independently by two authors; conflicts were adjudicated by a third author. Data were meta-analysed using Review Manager V.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-five RCTs reported NEC as an outcome. Seventeen reported surgical NEC; all RCTs were included. A variety of probiotic products was administered across studies. Description of surgical NEC in most studies was poor. Only 6/16 specifically reported incidence of surgery for NEC, 12/17 Bell’s stage 3 and 13/17 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 35 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.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:

View Full Text

Statistics from


  • Funding SE gratefully acknowledges support from Great Ormond Street Children’s Charity and the NIHR Great Ormond Street Biomedical Research Centre.

  • Disclaimer The funders had no input into the systematic review.

  • Competing interests SE has received consultancy fees from Fresenius-Kabi and a speakers honorarium from Danone.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.