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Current use of probiotics to prevent necrotising enterocolitis
  1. Samuel David Duffield1,
  2. Paul Clarke1,2
  1. 1 Neonatal Unit, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK
  2. 2 Norwich Medical School, University of East Anglia, Norwich, UK
  1. Correspondence to Prof. Paul Clarke, Neonatal Intensive Care Unit, Norfolk and Norwich University Hospital NHS Foundation Trust, Norwich, NR4 7UY, UK; paul.clarke{at}

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Each year in England ~230 babies born at <32 weeks’ gestation develop severe necrotising enterocolitis (NEC), with approximately half of them dying.1 Successive meta-analyses indicate that dual-strain probiotics—specifically the combination of Bifidobacterium and Lactobacillus species—significantly reduce the incidence of NEC in very low birthweight infants (VLBWI; <1500 g) and halve mortality.2–4 A 2014 national UK survey,4 done prior to the publication of the Probiotics in Preterm babies Study (PiPS) trial,5 showed that only 12% (7 of 58) of the UK tertiary neonatal intensive care units (NICUs) were using probiotics, while more than half were awaiting the PiPS results. We aimed to determine if the prevalence of probiotic use has changed since the publication of the PiPS study in 2015.

During June–July 2018, we telephone-surveyed all 58 UK tertiary-level NICUs. We asked a senior member of the medical team (registrar/advanced neonatal nurse practitioner/consultant) if their NICU was currently using probiotics for prophylaxis of NEC.

All 58 (100%) units responded. Only 10 (17%) currently used probiotics routinely, and all used multistrain formulations (Lactobacillus acidophilus plus ≥1 Bifidobacterium): n=7 Labinic Drops (Biofloratech, UK); n=3 Infloran (Desma Healthcare, Switzerland). There has been no significant increase in probiotics use in UK tertiary NICUs since 2014 (10 of 58 vs 7 of 58, p=0.6, χ2).

Notwithstanding the strong evidence of benefit from using dual-strain probiotics shown by meta-analyses,2 3 the large PiPS trial, which used a single-strain Bifidobacterium breve and had a null result, has likely influenced the wider adoption of probiotics in the UK. If current meta-analyses are misleading, then several hundred high-risk babies receive probiotics annually in the UK for no benefit, although at a small monetary cost to the National Health Service (NHS) but negligible risk otherwise. However, if the meta-analyses are not misleading, then thousands of high-risk UK babies (and their families) are being denied an important treatment that, with a risk reduction of ~0.5,2 3 would be preventing severe NEC in at least 100 babies born in England per year and saving the lives of at least 50 annually.

How to negotiate the impasse? Is a new large randomised controlled trial (RCT) of dual-strain prophylaxis required to finally adjudicate? It seems unlikely that such a trial will be done. Based on the 3% incidence of severe NEC in babies <32 weeks’ gestation,1 to show a halving of severe NEC incidence with a prophylactic dual-strain Lactobacillus–Bifidobacterium probiotic combination, a theoretical future RCT would require n=~3500 babies.

Meanwhile there is mounting supportive evidence from many countries that have already introduced dual-strain probiotics. In Germany most centres routinely offer probiotics below 32 weeks’ gestation and 70% of German VLBWI receive dual-strain probiotics,6 a stark contrast to UK practice. A large observational time-series analysis comparing n=5818 dual-strain probiotic-treated (Infloran) vs n=5072 untreated VLBWI from 44 German NICUs showed that probiotics were associated with markedly reduced NEC incidence (hazard ration (HR) 0.48, 95% CI 0.38 to 0.62), reduced overall mortality (HR 0.60, 95% CI 0.44 to 0.83) and post-NEC mortality (HR 0.51, 95% CI 0.26 to 0.99).7 These impressive findings mirror those of the meta-analyses.

One valid conclusion from the cumulated mass of current evidence is that widespread UK adoption of dual-strain probiotics for VLBWI would save the lives of >50 babies each year, not to mention the huge morbidity/cost burden to the NHS and to families of surviving babies with NEC. With such high stakes, a National Institute for Health and Care Excellence guideline making evidence-based recommendations on the clinical effectiveness and cost-effectiveness of probiotics to prevent NEC in preterm infants is urgently needed and would be universally welcomed.

Reliable up-to-date data on NEC incidence are needed from all UK NICUs, but there is a particular onus on probiotics-using centres to present their data. NEC rates may possibly have reduced generally in recent years in line with increased breast milk feeding. However, until a standardised, strict NEC working definition is agreed, any comparisons may be somewhat confounded.


The authors thank all colleagues who kindly responded to the survey by providing data regarding their units.



  • Contributors PC devised the study. SDD collected all the data. SDD and PC together drafted the manuscript and approved the final version.

  • Competing interests None declared.

  • Patient consent Not required.

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