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Lactobacillus reuteri DSM 17938 for managing infant colic: protocol for an individual participant data meta-analysis
  1. Valerie Sung1,
  2. Michael D Cabana2,
  3. Frank D'Amico3,
  4. Girish Deshpande4,5,
  5. Christophe Dupont6,
  6. Flavia Indrio7,
  7. Silja Mentula8,
  8. Anna Partty9,
  9. Francesco Savino10,
  10. Hania Szajewska11,
  11. Daniel Tancredi12
  1. 1Murdoch Childrens Research Institute, Royal Children's Hospital, The University of Melbourne, Melbourne, Victoria, Australia
  2. 2Department of Pediatrics, Epidemiology and Biostatistics, University of California, San Francisco (UCSF) School of Medicine, San Francisco, California, USA
  3. 3Duquesne University/UPMC St. Margaret Hospital, Pittsburgh, Pennsylvania, USA
  4. 4Department of Children's health division and NICU, Nepean Hospital Sydney, Sydney, New South Wales, Australia
  5. 5Sydney Medical School Nepean, University of Sydney, Sydney, New South Wales, Australia
  6. 6Department of Pediatric Gastroenterology, Paris Descartes University, Necker Hospital, Paris, France
  7. 7Department of Pediatrics, University of Bari, Bari, Italy
  8. 8Bacteriology Unit, National Institute for Health and Welfare, Helsinki, Finland
  9. 9Department of Pediatrics and Adolescent Medicine, Turku University Hospital, Turku, Finland
  10. 10Ospedale Infantile Regina Margherita, Città della Salute e della Scienza di Torino, Torino, Italy
  11. 11Department of Paediatrics, The Medical University of Warsaw, Warsaw, Poland
  12. 12Department of Pediatrics, UC Davis Health System, Sacramento, California, USA
  1. Correspondence to Dr Valerie Sung; valerie.sung{at}


Introduction Infant colic, or excessive crying of unknown cause in infants less than 3 months old, is common and burdensome. Its aetiology is undetermined, and consensus on its management is still lacking. Recent studies suggest a possible link between infant colic and gut microbiota, indicating probiotics to be a promising treatment. However, only a few strains have been tested, and results from randomised controlled trials are conflicting. It is important to clarify whether probiotics are effective for treating infant colic in general, and to identify whether certain subgroups of infants with colic would benefit from particular strains of probiotics.

Methods and analysis Through an individual participant data meta-analysis (IPDMA), we aim to identify whether the probiotic Lactobacillus reuteri DSM 17938 is effective in the management of infant colic, and to clarify whether its effects differ according to feeding method (breast vs formula vs combined), proton pump inhibitor exposure, and antibiotic exposure. The primary outcomes are infant crying duration and treatment success (at least 50% reduction in crying time from baseline) at 21 days postintervention. Individual participant data from all studies will be modelled simultaneously in multilevel generalised linear mixed-effects regression models to account for the nesting of participants within studies. Subgroup analyses of participant-level and intervention-level characteristics will be undertaken on the primary outcomes to assess if the intervention effect differs between certain groups of infants.

Ethics and dissemination Approved by the Royal Children's Hospital Human Research Ethics Committee (HREC 34081). Results will be reported in a peer-reviewed journal in 2015.

Trial registration number PROSPERO CRD42014013210.


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