title: Lactobacillus reuteri DSM 17938 for managing infant colic: protocol for an individual participant data meta-analysis.
abstract: BACKGROUND
  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
  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.
  
  
  BACKGROUND
  Approved by the Royal Children's Hospital Human Research Ethics Committee (HREC 34081). Results will be reported in a peer-reviewed journal in 2015.
  
  
  BACKGROUND
  PROSPERO CRD42014013210.
authors.affiliation: Murdoch Childrens Research Institute, Royal Children's Hospital, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Valerie
authors.initials: V
authors.lastname: Sung
authors.affiliation: Department of Pediatrics, Epidemiology and Biostatistics, University of California, San Francisco (UCSF) School of Medicine, San Francisco, California, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Cabana
authors.affiliation: Duquesne University/UPMC St. Margaret Hospital, Pittsburgh, Pennsylvania, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: D'Amico
authors.affiliation: Department of Children's health division and NICU, Nepean Hospital Sydney, Sydney, New South Wales, Australia Sydney Medical School Nepean, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Girish
authors.initials: G
authors.lastname: Deshpande
authors.affiliation: Department of Pediatric Gastroenterology, Paris Descartes University, Necker Hospital, Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Dupont
authors.affiliation: Department of Pediatrics, University of Bari, Bari, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: Indrio
authors.affiliation: Bacteriology Unit, National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Silja
authors.initials: S
authors.lastname: Mentula
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Turku University Hospital, Turku, Finland.
authors.forename: Anna
authors.initials: A
authors.lastname: Partty
authors.affiliation: Ospedale Infantile Regina Margherita, Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Savino
authors.affiliation: Department of Paediatrics, The Medical University of Warsaw, Warsaw, Poland.
authors.forename: Hania
authors.initials: H
authors.lastname: Szajewska
authors.affiliation: Department of Pediatrics, UC Davis Health System, Sacramento, California, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Tancredi
mesh_terms: D006801:Humans; D007223:Infant; D003085:Colic / Q000628:therapy; D052200:Limosilactobacillus reuteri; D015201:Meta-Analysis as Topic; D019936:Probiotics / Q000627:therapeutic use; D016896:Treatment Outcome
keywords: COMPLEMENTARY MEDICINE; NUTRITION & DIETETICS; PERINATOLOGY