More than 10,000 preterm infants have participated in randomised controlled trials on probiotics worldwide, suggesting that probiotics in general could reduce rates of necrotising enterocolitis (NEC), sepsis, and mortality. Answers to relevant clinical questions as to which strain to use, at what dosage, and how long to supplement are, however, not available. On the other hand, an increasing number of commercial products containing probiotics are available from sometimes suboptimal quality. Also, a large number of units around the world are routinely offering probiotic supplementation as the standard of care despite lacking solid evidence. Our recent network meta-analysis identified probiotic strains with greatest efficacy regarding relevant clinical outcomes for preterm neonates. Efficacy in reducing mortality and morbidity was found for only a minority of the studied strains or combinations. In the present position paper, we aim to provide advice, which specific strains might potentially be used and which strains should not be used. In addition, we aim to address safety issues of probiotic supplementation to preterm infants, who have reduced immunological capacities and occasional indwelling catheters. For example, quality reassurance of the probiotic product is essential, probiotic strains should be devoid of transferable antibiotic resistance genes, and local microbiologists should be able to routinely detect probiotic sepsis. Provided all safety issues are met, there is currently a conditional recommendation (with low certainty of evidence) to provide either Lactobacillus rhamnosus GG ATCC53103 or the combination of Bifidobacterium infantis Bb-02, Bifidobacterium lactis Bb-12, and Streptococcus thermophilus TH-4 in order to reduce NEC rates.

Childhood Nutrition Research Centre UCL GOS Institute of Child Health London UK

Children's Hospital Zagreb University of Zagreb School of Medicine University J J Strossmayer School of Medicine Osijek Croatia

CNRC Baylor College of Medicine Houston TX

Department of Clinical Sciences Paediatrics Umeå University Umeå Sweden

Department of Gastroenterology Hepatology and Nutrition University Medical Centre Ljubljana University Children's Hospital Ljubljana Slovenia

Department of Paediatric Gastroenterology Ospedale Pediatrico Giovanni XXIII University of Bari Italy

Department of Paediatrics Neonatology Amsterdam UMC University of Amsterdam and Vrije Universiteit Amsterdam Emma Children's Hospital Amsterdam The Netherlands

Department of Paediatrics The Medical University of Warsaw Poland

Department of Paediatrics Ulm University and Helios Hospital Pforzheim Germany

Department of Paediatrics University Hospital Motol Prague Czech Republic

Department of Paediatrics University of Granada Spain

Department of Translational Medical Science Section of Paediatrics University Federico 2 Naples Italy

Division of Gastroenterology Hepatology and Nutrition Department of Paediatrics Hospital for Sick Children Toronto Canada

Faculty of Health Sciences Ben Gurion University Beer Sheva Israel

Institute for Gastroenterology Nutrition and Liver Diseases Schneider Children's Medical Center Sackler Faculty of Medicine Tel Aviv University Israel

Kidz Health Castle UZ Brussel Vrije Universiteit Brussel Brussels Belgium

Newcastle Neonatal Service Newcastle Hospitals NHS Trust and Newcastle University Newcastle upon Tyne UK

Paris Descartes University APHP Necker Enfants Malades hospital Paris France

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