Background: Respiratory tract infections (RTI) are among the leading causes of hospitalisation and death for children under 5 years. We aimed to determine if neonatal BCG vaccination reduces early life hospitalisations for lower RTI (LRTI) in a low-tuberculosis endemic setting.

Methods: Neonates were randomised 1:1 to receive BCG-Denmark vaccination (BCG group) or no intervention (Control) in a phase 3 randomised controlled trial in Australia (NCT01906853). Hospitalisation for infection was determined by parent-reported questionnaires. The effect of BCG vaccination on the incidence of hospitalisation for LRTI in the first five years was analysed by intention-to-treat with multiple imputation.

Results: Complete case data to five years was available for 711 (56 %) of the 1272 participants. In the time-to-event analysis of the 1272 infants randomised, 14.2 % had one or more hospitalisations due to infection by five years. The predominant cause of hospitalisation for infection was LRTI in the first year of life (37 % of first hospitalisations), and upper RTI (33 %) by five years. In the multiple imputation analysis of the 1272 participants, the adjusted incidence of hospitalisation for LRTI in the first five years was 9.6 % in the BCG group compared to 12.4 % in the Control group (adjusted risk difference [aRD] -2.8 percentage points; 95 % CI -7.8 to 2.3). Secondary outcomes of hospitalisation for any infection and any respiratory illness were also lower in the BCG group. No interaction was observed between the effect of BCG vaccination on hospitalisation for LRTI and maternal BCG vaccination, sex or delivery mode.

Conclusions: In a low-mortality setting, there was not clear evidence that neonatal BCG vaccination significantly reduces the incidence of early life hospitalisation for LRTI, infections or respiratory illness. The ability to detect any effect of BCG may have been limited by the increasing missing data over the course of follow-up.