Neonatal Bacille Calmette-Guérin Vaccination and Infections in the First Year of Life: The MIS BAIR Randomized Controlled Trial

Nicole L Messina; Laure F Pittet; Kaya Gardiner; Bridget Freyne; Kate L Francis; Christel Zufferey; Veronica Abruzzo; Clare Morrison; Katrina J Allen; Katie L Flanagan; Anne-Louise Ponsonby; Roy Robins-Browne; Frank Shann; Mike South; Peter Vuillermin; Susan Donath; Dan Casalaz; Nigel Curtis

doi:10.1093/infdis/jiab306

Neonatal Bacille Calmette-Guérin Vaccination and Infections in the First Year of Life: The MIS BAIR Randomized Controlled Trial

J Infect Dis. 2021 Oct 13;224(7):1115-1127. doi: 10.1093/infdis/jiab306.

Authors

Nicole L Messina^{1

2}, Laure F Pittet^{1

3}, Kaya Gardiner^{1

3}, Bridget Freyne^{1

2

4}, Kate L Francis¹, Christel Zufferey¹, Veronica Abruzzo¹, Clare Morrison¹, Katrina J Allen⁵, Katie L Flanagan^{6

7

8}, Anne-Louise Ponsonby^{1

2}, Roy Robins-Browne^{1

2}, Frank Shann², Mike South^{1

2

3}, Peter Vuillermin^{1

9

10}, Susan Donath^{1

2}, Dan Casalaz¹¹, Nigel Curtis^{1

2

3}

Affiliations

¹ Infectious Diseases; Clinical Epidemiology and Biostatistics Unit; Population Allergy, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
² Departments of Paediatrics; Microbiology and Immunology, The University of Melbourne, Parkville, Victoria, Australia.
³ Infection Diseases Unit; Department of General Medicine; Department of Research Operations, The Royal Children's Hospital, Parkville, Victoria, Australia.
⁴ Institute of Infection and Global Health University of Liverpool and Malawi-Liverpool Wellcome Trust Research Programme, Liverpool, United Kingdom.
⁵ Formerly of Centre for Food and Allergy Research, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
⁶ School of Health Sciences, University of Tasmania, Launceston, Tasmania, Australia.
⁷ School of Health and Biomedical Science, RMIT University, Melbourne, Victoria, Australia.
⁸ Department of Immunology and Pathology, Monash University, Melbourne, Victoria, Australia.
⁹ School of Medicine, Deakin University, Geelong, Victoria, Australia.
¹⁰ Child Health Research Unit, Barwon Health, Geelong, Victoria, Australia.
¹¹ Neonatal Intensive Care Unit, Mercy Hospital for Women, Heidelberg, Victoria, Australia.

PMID: 34146093
DOI: 10.1093/infdis/jiab306

Abstract

Background: Bacille Calmette-Guérin (BCG) vaccination has beneficial off-target effects that may include protecting against non-mycobacterial infectious diseases. We aimed to determine whether neonatal BCG vaccination reduces lower respiratory tract infections (LRTI) in infants in the Melbourne Infant Study: BCG for Allergy and Infection Reduction (MIS BAIR) trial.

Methods: In this investigator-blinded trial, neonates in Australia were randomized to receive BCG-Denmark vaccination or no BCG at birth. Episodes of LRTI were determined by symptoms reported in parent-completed, 3-month questionnaires over the first year of life. Data were analyzed by intention-to-treat using binary regression.

Results: A total of 1272 neonates were randomized to the BCG vaccination (n = 637) or control (n = 635) group. The proportion of participants with an episode of LRTI in the first year of life among BCG-vaccinated infants was 54.8% compared to 58.0% in the control group, resulting in a risk difference of -3.2 (95% confidence interval, -9.0 to 2.6) after multiple imputation. There was no interaction observed between the primary outcome and sex, maternal BCG, or the other prespecified effect modifiers.

Conclusions: Based on the findings of this trial, there is insufficient evidence to support the use of neonatal BCG vaccination to prevent LRTI in the first year of life in high-income settings.

Keywords: BCG; infant; infection; nonspecific; off-target.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Australia / epidemiology
BCG Vaccine / administration & dosage*
Female
Fever / epidemiology
Humans
Infant
Infant, Newborn
Infections / epidemiology
Male
Pregnancy
Respiratory Tract Infections / epidemiology*
Respiratory Tract Infections / prevention & control
Vaccination

Substances

BCG Vaccine