title: Probiotic supplementation during pregnancy or infancy for the prevention of asthma and wheeze: systematic review and meta-analysis.
abstract: OBJECTIVE
  To evaluate the association of probiotic supplementation during pregnancy or infancy with childhood asthma and wheeze.
  
  
  METHODS
  Systematic review and meta-analysis of randomised controlled trials.
  
  
  METHODS
  Medline, Embase, and Central (Cochrane Library) databases from inception to August 2013, plus the World Health Organization's international clinical trials registry platform and relevant conference proceedings for the preceding five years. Included trials and relevant reviews were forward searched in Web of Science.
  
  
  METHODS
  Two reviewers independently identified randomised controlled trials evaluating probiotics administered to mothers during pregnancy or to infants during the first year of life. The primary outcome was doctor diagnosed asthma; secondary outcomes included wheeze and lower respiratory tract infection.
  
  
  RESULTS
  We identified 20 eligible trials including 4866 children. Trials were heterogeneous in the type and duration of probiotic supplementation, and duration of follow-up. Only five trials conducted follow-up beyond participants' age of 6 years (median 24 months), and none were powered to detect asthma as the primary outcome. The overall rate of doctor diagnosed asthma was 10.7%; overall rates of incident wheeze and lower respiratory tract infection were 33.3% and 13.9%, respectively. Among 3257 infants enrolled in nine trials contributing asthma data, the risk ratio of doctor diagnosed asthma in participants randomised to receive probiotics was 0.99 (95% confidence interval 0.81 to 1.21, I(2)=0%). The risk ratio of incident wheeze was 0.97 (0.87 to 1.09, I(2)=0%, 9 trials, 1949 infants). Among 1364 infants enrolled in six trials, the risk ratio of lower respiratory tract infection after probiotic supplementation was 1.26 (0.99 to 1.61, I(2)=0%). We adjudicated most trials to be of high (ten trials) or unclear (nine trials) risk of bias, mainly due to attrition.
  
  
  CONCLUSIONS
  We found no evidence to support a protective association between perinatal use of probiotics and doctor diagnosed asthma or childhood wheeze. Randomised controlled trials to date have not yielded sufficient evidence to recommend probiotics for the primary prevention of these disorders. Extended follow-up of existing trials, along with further clinical and basic research, are needed to accurately define the role of probiotics in the prevention of childhood asthma.
  
  
  BACKGROUND
  PROSPERO (CRD42013004385).
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, AB, Canada T6G 1C9.
authors.forename: Meghan B
authors.initials: MB
authors.lastname: Azad
authors.forename: J Gerard
authors.initials: JG
authors.lastname: Coneys
authors.forename: Anita L
authors.initials: AL
authors.lastname: Kozyrskyj
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Field
authors.forename: Clare D
authors.initials: CD
authors.lastname: Ramsey
authors.forename: Allan B
authors.initials: AB
authors.lastname: Becker
authors.forename: Carol
authors.initials: C
authors.lastname: Friesen
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Abou-Setta
authors.forename: Ryan
authors.initials: R
authors.lastname: Zarychanski
mesh_terms: D001249:Asthma / Q000453:epidemiology / Q000517:prevention & control*; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D007223:Infant; D011247:Pregnancy; D019936:Probiotics / Q000009:adverse effects / Q000627:therapeutic use*; D012135:Respiratory Sounds / Q000187:drug effects*; D016896:Treatment Outcome