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Necrotising enterocolitis, late-onset sepsis and mortality after routine probiotic introduction in the UK
  1. Claire Granger1,2,
  2. Elda Dermyshi1,
  3. Eve Roberts3,
  4. Lauren C Beck2,
  5. Nicholas Embleton1,3,
  6. Janet Berrington1,2
  1. 1 Newcastle Neonatal Service, Ward 35 Neonatal Unit, Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
  2. 2 Translational and Clinical Research Institute, Newcastle University Faculty of Medical Sciences, Newcastle upon Tyne, UK
  3. 3 Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK
  1. Correspondence to Dr Janet Berrington, Newcastle Neonatal Service, Ward 35 Neonatal Unit, Royal Victoria Infirmary, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK; j.e.berrington{at}


Objective To compare necrotising enterocolitis (NEC), late-onset sepsis (LOS), focal intestinal perforation (FIP) and mortality in infants from a single neonatal unit before and after probiotic introduction.

Design Retrospective review of infants <32 weeks admitted January 2009–December 2012 (no probiotic) and January 2013–December 2017 (routine probiotics). Infants included were admitted before day 3, and not transferred out before day 3. NEC, LOS and FIP were defined with standard definitions.

Patients 1061 infants were included, 509 preprobiotic and 552 postprobiotic. Median gestation, birth weight and antenatal steroid use did not differ, and proportions of extremely low birthweight infants were similar (37% and 41%).

Results Overall unadjusted risk of NEC (9.2% (95% CI 7.1 to 12.1) vs 10.6% (95% CI 8.2 to 13.4), p=0.48), LOS (16.3% (95% CI 13.2 to 19.6) vs 14.1% (95% CI 11.5 to 17.4), p=0.37) and mortality (9.2% (95% CI 7.1 to 12.1) vs 9.7% (95% CI 7.6 to 12.6), p=0.76) did not differ, nor proportion of surgical NEC. In multiple logistic regression, accounting for gestation, birth weight, antenatal steroid, maternal milk, chorioamnionitis and sex, probiotic receipt was not significantly associated with NEC (adjusted OR (aOR) 1.08 (95% CI 0.71 to 1.68), p=0.73), LOS or mortality. In subgroup (645 infants) >28 weeks, aOR for NEC in the probiotic cohort was 0.42 (95% CI 0.2 to 0.99, p=0.047). FIP was more common in the probiotic cohort (OR 2.3 (95% CI 1.0 to 5.4), p=0.04), not significant in regression analysis (2.11 (95% CI 0.97 to 4.95), p=0.05).

Conclusions Probiotic use in this centre did not reduce overall mortality or rates of NEC, LOS or FIP but subgroup analysis identified NEC risk reduction in infants >28 weeks, and LOS reduction <28 weeks.

  • neonatology
  • gastroenterology

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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  • Twitter @clairelgranger, @neonatalbiobank

  • Contributors JB was responsible for the initial study concept and methodology. JB, NE and CG were responsible for data collection and analysis. CG and JB wrote the initial manuscript. LCB, CG and JB undertook statistical and regression analysis.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests NE and JB declare institutional research funding from Prolacta Biosciences and Danone Early Life Nutrition, and honoraria from Danone Early Life Nutrition, and Nestle Nutrition Institute. The other authors declare that they have no competing interests.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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