Probiotic supplementation during pregnancy or infancy for the prevention of asthma and wheeze: systematic review and meta-analysisBMJ 2013; 347 doi: https://doi.org/10.1136/bmj.f6471 (Published 04 December 2013) Cite this as: BMJ 2013;347:f6471
- Meghan B Azad, Banting postdoctoral fellow1,
- J Gerard Coneys, core resident2,
- Anita L Kozyrskyj, associate professor 1,
- Catherine J Field, professor4,
- Clare D Ramsey, assistant professor and attending physician23,
- Allan B Becker, senior investigator and section head of allergy and immunology56,
- Carol Friesen, librarian78,
- Ahmed M Abou-Setta, research associate7,
- Ryan Zarychanski, attending physician, assistant professor, and director of knowledge synthesis237
- 1Department of Pediatrics, University of Alberta, Edmonton, AB, Canada T6G 1C9
- 2Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada
- 3Department of Community Health Sciences, University of Manitoba, Canada
- 4Department of Agriculture, Food and Nutritional Sciences, University of Alberta
- 5Manitoba Institute of Child Health, Winnipeg, Canada
- 6Pediatrics and Child Health, University of Manitoba, Canada
- 7George & Fay Yee Centre for Healthcare Innovation, University of Manitoba/Winnipeg Regional Health Authority, Winnipeg, Canada
- 8Neil John Maclean Health Sciences Library, University of Manitoba Libraries, Winnipeg, Canada
- Correspondence to: M B Azad
- Accepted 8 October 2013
Objective To evaluate the association of probiotic supplementation during pregnancy or infancy with childhood asthma and wheeze.
Design Systematic review and meta-analysis of randomised controlled trials.
Data sources 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.
Review 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, I2=0%). The risk ratio of incident wheeze was 0.97 (0.87 to 1.09, I2=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, I2=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.
Systematic review registration PROSPERO (CRD42013004385).
We thank the George and Fay Yee Centre for Healthcare Innovation for infrastructure support, and the following authors for providing unpublished data: G T Rijkers (University College Roosevelt Academy, The Netherlands) D M W Gorissen (University Medical Centre Utrecht, The Netherlands), J Hol (St Elisabeth Hospital, Curacao), P Steenhout (Nestec), K Kukkonen and E Savilahti (Helsinki University Central Hospital, Finland), and K Wickens (University of Otago, New Zealand).
Contributors: MBA, AMA-S, and RZ conceived and designed the study with input from ABB, CJF, CDR, and ALK. CF provided guidance on search strategies. MBA and JGC screened and reviewed studies, extracted data, and assessed the quality of included trials. MBA analysed the data and all authors contributed to its interpretation. MBA drafted the manuscript and all authors participated in the revision process and have approved this submission for publication. MBA is guarantor, had full access to all of the data in the study, and can take responsibility for the integrity of the data and the accuracy of the data analysis.
Funding: No specific funding was obtained for this study. MBA is a Canadian Institutes of Health Research Banting postdoctoral fellow, and recipient of a Parker B Francis research opportunity award and Alberta Innovates Health Solutions incentive award. RZ is a recipient of a randomised controlled trial mentorship award from the Canadian Institute of Health Research. ALK is the research chair in maternal-child health and the environment at the Women and Children’s Health Research Institute. None of the funders influenced the conduct of this research.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: As this study did not involve the collection of new data, but rather the analysis of data from previously published research, no ethics approval was sought.
Data sharing: The RevMan file used to generate summary effect measures will be made available on request.
MBA, as guarantor, affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned and registered have been explained.
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