Neonatal BCG vaccination and infections in the first year of life: the MIS BAIR randomised controlled trial.

Background Bacille Calmette-Guerin (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 MIS BAIR trial. Methods In this investigator-blinded trial, neonates in Australia were randomised to receive BCG-Denmark vaccination or no BCG at birth. Episodes of LRTI were determined by symptoms reported in parent-completed 3-monthly questionnaires over the first year of life. Data were analysed by intention-to-treat using binary regression. Clinicaltrials.gov (NCT01906853). Results From August 2013 to September 2016, 1272 neonates were randomised 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% CI -9.0 to 2.6) after multiple imputation. There was no interaction observed between the primary outcome and sex, maternal BCG or the other pre-specified 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.