Neonatal BCG vaccination to prevent respiratory infections in the first 5 years of life: results from the MIS BAIR randomised controlled trial

Nicole L Messina ¹, Laure F Pittet ², Emily K Forbes ³

¹Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia; Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
²Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia; Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia; Immunology, Vaccinology, Rheumatology and Infectious Diseases Unit, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
³Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
⁴Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia; Clinical Epidemiology & Biostatistics Unit, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
⁵Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Research Operations, The Royal Children's Hospital Melbourne, Parkville, Victoria, Australia.
⁶School of Medicine, University of Tasmania, Hobart, Tasmania, Australia; School of Health and Biomedical Science, RMIT University, Melbourne, Victoria, Australia; Centre for Infectious Diseases and Microbiology, Westmead Hospital, Sydney, New South Wales, Australia.
⁷Population Allergy, Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia.
⁸Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria, Australia.
⁹Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia.
¹⁰Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia; Department of General Medicine, The Royal Children's Hospital Melbourne, Parkville, Victoria, Australia.
¹¹Institute of Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Victoria, Australia; Child Health Research Unit, Barwon Health, Geelong, Victoria, Australia.
¹²Neonatal Intensive Care Unit, Mercy Hospital for Women, Heidelberg, Victoria, Australia.
¹³Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia; Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Infectious Diseases, The Royal Children's Hospital Melbourne, Parkville, Victoria, Australia.

⁰Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia; Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia.

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December 3, 2025

View abstract on PubMed

Summary

Neonatal BCG vaccination did not significantly reduce hospitalizations for lower respiratory tract infections (LRTI) in young children in Australia. Further research is needed to confirm BCG's protective effects in low-tuberculosis settings.

Area Of Science

Pediatrics
Immunology
Infectious Diseases

Background

Respiratory tract infections (RTI) are a major cause of hospitalization and death in children under five.
The effectiveness of neonatal Bacillus Calmette-Guérin (BCG) vaccination in preventing early-life lower respiratory tract infections (LRTI) requires investigation in low-tuberculosis endemic regions.

Purpose Of The Study

To evaluate if neonatal BCG vaccination reduces hospitalizations for LRTI in children up to five years of age.
To assess the impact of BCG vaccination on overall infection and respiratory illness hospitalizations in early childhood.

Main Methods

A phase 3 randomized controlled trial in Australia assigned neonates to receive BCG-Denmark vaccination or no intervention.
Hospitalizations for infection were recorded via parent-reported questionnaires.
Intention-to-treat analysis with multiple imputation was used to analyze LRTI hospitalization incidence over five years.

Main Results

Complete data to five years was available for 56% of participants (711/1272).
The adjusted incidence of LRTI hospitalization by five years was 9.6% in the BCG group versus 12.4% in the control group (aRD -2.8%; 95% CI -7.8 to 2.3).
Secondary outcomes for any infection and respiratory illness hospitalizations were also lower in the BCG group, though not statistically significant.

Conclusions

Neonatal BCG vaccination did not provide clear evidence of significantly reducing early-life hospitalizations for LRTI, infections, or respiratory illness in this low-mortality setting.
Increasing missing data over follow-up may have limited the study's ability to detect a significant effect of BCG vaccination.

Keywords:

BCG vaccine (Mycobacterium bovis) Hospitalisation LRTI Non-specific effects Off-target effects Prevention Vaccine

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