Probiotic supplementation during pregnancy or infancy for the prevention of asthma and wheeze: systematic review and meta-analysis

Meghan B Azad, J Gerard Coneys, Anita L Kozyrskyj, Catherine J Field, Clare D Ramsey, Allan B Becker, Carol Friesen, Ahmed M Abou-Setta, Ryan Zarychanski, Meghan B Azad, J Gerard Coneys, Anita L Kozyrskyj, Catherine J Field, Clare D Ramsey, Allan B Becker, Carol Friesen, Ahmed M Abou-Setta, Ryan Zarychanski

Abstract

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, 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.

Systematic review registration: PROSPERO (CRD42013004385).

Conflict of interest statement

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.

Figures

https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4793452/bin/azam013493.f1_default.jpg
Fig 1 Study flow diagram, following PRISMA criteria with modifications
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4793452/bin/azam013493.f2_default.jpg
Fig 2 Probiotic supplementation during pregnancy or infancy and doctor diagnosed asthma in children. The longest available follow-up data (intention to treat) were extracted from each contributing trial. Trials are sorted in order of decreasing duration of follow-up. df=degrees of freedom; M-H=Mantel-Haenszel
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4793452/bin/azam013493.f3_default.jpg
Fig 3 Probiotic supplementation during pregnancy or infancy and incident wheeze in children. The longest available follow-up data (intention to treat) were extracted from each contributing trial. Trials are sorted in order of decreasing duration of follow-up. df=degrees of freedom; M-H=Mantel-Haenszel
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4793452/bin/azam013493.f4_default.jpg
Fig 4 Probiotic supplementation during pregnancy or infancy and lower respiratory tract infection in children. The longest available follow-up data (intention to treat) were extracted from each contributing trial. Trials are sorted in order of decreasing duration of follow-up, and subgrouped according to whether the incidence of lower respiratory tract infection was systematically reported as a primary or secondary outcome, or as an adverse event. AE=adverse event; df=degrees of freedom; LRTI=lower respiratory tract infection; M-H=Mantel-Haenszel

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