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J Pediatr Gastroenterol Nutr. 2018 Jan 30. doi: 10.1097/MPG.0000000000001897. [Epub ahead of print]

Probiotics for Preterm Infants: a strain specific systematic review and network meta-analysis.

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Department of Paediatrics, Emma Children's Hospital - AMC, Amsterdam, The Netherlands.
Department of Paediatrics, VU University Medical Center, Amsterdam, The Netherlands.
Department of Paediatrics, The Medical University of Warsaw, Poland.
Newcastle Neonatal Service, Newcastle Hospitals NHS Trust and Newcastle University, Newcastle upon Tyne, UK.
Children's Hospital Zagreb, University of Zagreb School of Medicine, Croatia.
Department of Epidemiology, University Medical Center Groningen, The Netherlands.
Institute for Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Israel.
Department of Translational Medical Sciences and European Laboratory for the Investigation of Food Induced Diseases and CEINGE Advanced Biotechnologies and Task Force on Investigations on Microbiome, University Federico II, Naples Italy
Department of Clinical Sciences, Paediatrics, Umeå University, Umeå, Sweden
Department of Paediatric Gastroenterology division, OspedalePediatrico Giovanni XXIII University of Bari Italy
Department of Paediatrics, Ulm University and Helios Hospital Pforzheim, Germany
University Medical Centre Ljubljana, University Children's Hospital Ljubljana, Department of Gastroenterology, Hepatology and Nutrition
Kidz Health Castle, UZ Brussel, Vrije Universiteit Brussel, Brussels, Belgium
Faculty of Health Sciences, Ben-Gurion University, Beer-Sheva, Israel



Several randomised controlled trials (RCTs) on the use of probiotics to reduce morbidity and mortality in preterm infants have provided inconsistent results. Whilst meta-analyses that group all of the used strains together, suggest efficacy, it is not possible to determine the most effective strain which is more relevant to the clinician. We therefore used a network meta-analysis (NMA) approach in order to identify strains with greatest efficacy.


A PubMed search identified placebo-controlled or head-to-head RCTs investigating probiotics in preterm infants. From trials that recorded mortality, necrotising enterocolitis (NEC), late-onset sepsis (LOS), or time until full enteral feeding (TUFEF) as outcomes, data were extracted and Bayesian hierarchical random effects models were run to construct a NMA.


Fifty-one RCTs involving 11,231 preterm infants were included. Most strains or combinations of strains were only studied in one or a few RCTs. Only 3 out of 25 studied probiotic treatment combinations showed significant reduction in mortality rates. Seven treatments reduced NEC incidence, 2 reduced LOS, and 3 reduced TUFEF. There was no clear overlap of strains which were effective on multiple outcome domains.


This NMA showed efficacy in reducing mortality and morbidity only in a minority of the studied strains or combinations. This may be due to an inadequate number, or size, of RCTs, or due to a true lack of effect for certain species. Further large and adequately powered RCTs using strains with the greatest apparent efficacy will be needed in order to more precisely define optimal treatment strategies.

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