Neonatal BCG-vaccination has no effect on recurrent wheeze in the first year of life. A randomized clinical trial

BACKGROUND: Recurrent wheeze is frequent in childhood. Studies have suggested that Bacillus Calmette-Guérin (BCG) vaccination may have non-specific effects, reducing general non-tuberculosis morbidity, including respiratory infections and atopic diseases. The mechanisms behind these non-specific effects of BCG are not fully understood, but a shift from Th2 to Th1-response has been suggested as a possible explanation.

OBJECTIVE: We hypothesized that BCG at birth would reduce the cumulative incidence of recurrent wheeze during the first year of life.

METHODS: The Danish Calmette Study is a multicenter randomized trial conducted from 2012-2015 at three Danish hospitals. The 4262 newborns of 4184 included mothers were randomized 1:1 to BCG (SSI strain 1331) or to a no-intervention control group within 7 days of birth; siblings were randomized together as one randomization unit. Exclusion criteria were gestational age <32 weeks, birth weight <1000g, known immunodeficiency, or no Danish-speaking parent. Information was collected through telephone interviews and clinical examinations at 3 and 13 months of age; the data collectors were blinded to randomization group. Recurrent wheeze was defined in several ways, the main definition being: "physician-diagnosed and medically treated recurrent wheeze up to 13 months of age".

RESULTS: By 13 months 211/2100 (10.0%) children in the BCG group and 195/2071 (9.4%) children in the control group had been diagnosed by a medical doctor with recurrent wheeze and received anti-asthmatic treatment (relative risk 1.07 (95% confidence intervals 0.89-1.28)). Supplementary analyses were made, including an analysis of baseline risk factors for developing RW.

CONCLUSION: Neonatal BCG had no effect on the development of recurrent wheeze before 13 months of age.