Neonatal BCG vaccination to prevent asthma: Results from the MIS BAIR randomized controlled trial

Pittet LF, Forbes EK, Donath S, et al. Pediatr Allergy Immunol. 2025; 36:e70110. doi:10.1111/pai.70110

Abstract

Background

Asthma has a significant impact worldwide, but prevention strategies remain limited. We aimed to evaluate the efficacy of neonatal BCG vaccination in preventing asthma by modulating early-life immunity.

Methods

The Melbourne Infant Study: BCG for Allergy and Infection Reduction (MIS BAIR) was a phase 3 multicentre randomized controlled trial in Victoria, Australia. Infants were randomly assigned to receive the BCG-Denmark vaccine or no intervention within 10 days of birth. The incidence of asthma at 5 years of age was estimated using the International Study of Asthma and Allergies in Childhood questions. ClinicalTrial.gov (NCT01906853).

Results

Difference in presence and severity of asthma between BCG and
control groups, assessed at 5 years of age. 

A total of 1272 infants were randomized. The adjusted incidence of asthma was 14.4% in the BCG group compared to 16.0% in the control group (adjusted risk difference [aRD] −1.7 percentage points; 95%CI −7.4, 3.9). Secondary outcomes, including severe asthma and use of preventer medication, showed similar trends, with an aRD of −3.9 (95%CI −7.7, 0.0), and −5.6 (95%CI −10.9, −0.4), respectively, favoring the BCG group.

Among participants with one or both parents asthmatic, the rate of asthma was also lower in the BCG group (17.6%) compared with the control group (24.7%; aRD −7.2; 95%CI −15.9, 1.5), although a test for interaction was not significant (p = .07).

Conclusions

While the point estimates suggested BCG vaccination might protect against asthma, the wide uncertainty around the estimates means further studies with larger sample sizes are needed to evaluate the long-term benefits of BCG vaccination beyond its primary indication.

Key message

Asthma remains a global health burden with limited preventive strategies. In the Melbourne Infant Study: BCG for Allergy and Infection Reduction (MIS BAIR) randomized controlled trial, neonatal BCG vaccination was associated with a modest reduction in asthma outcomes, particularly severe asthma and in high-risk children. However, the uncertainty interval around the modest reduction did not indicate a clear, consistent benefit, and therefore further research is needed to clarify BCG's long-term effects.

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