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

The BMJ

Dec 2013

DOI: 10.1136/bmj.f6471

Citations:201

Influential Citations:2

Systematic Reviews / Meta-Analyses

Enhanced Details

Methods

Randomized, double-blind, placebo-controlled trials evaluating probiotic supplementation given to mothers during pregnancy or to healthy infants under 1 year. 20 trials included, 4,866 infants. Populations included high-risk for asthma (family history/allergic disease) and unselected; most trials in Europe, with some in Australia, New Zealand, and Taiwan. Follow-up ranged from 4 months to 8 years.

Intervention

Oral probiotic regimens given to pregnant women during pregnancy and/or to healthy infants in the first year of life. Daily doses ranged from 1×10^8 to 1×10^11 CFU, duration 1–25 months (median ~6 months). Administration methods included capsules, oil drops, or suspensions in water, milk, or infant formula; some regimens used combinations of strains and/or synbiotics (probiotic plus prebiotic). Timing included prenatal, postnatal, or both.

Results

No evidence of a protective association between perinatal probiotic supplementation and doctor-diagnosed asthma or childhood wheeze. Asthma RR 0.99 (95% CI 0.81–1.21); wheeze RR 0.97 (95% CI 0.87–1.09); lower respiratory tract infection RR 1.26 (95% CI 0.99–1.61). Subgroups showed no significant benefit. Conclusion: probiotics cannot be recommended for primary prevention of asthma or wheeze; extended follow-up and further research needed to define any role and safety considerations.

Limitations

Heterogeneous probiotic strains, doses, durations, and delivery methods; most trials not powered for asthma; follow-up median ~24 months; several trials with high or unclear risk of bias due to attrition or unblinding; safety outcomes incompletely reported; many trials industry-funded; inability to identify optimal strain or regimen for prevention.

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, 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). show less