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.


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


  • BCG Vaccine