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

Lisbeth Marianne Thøstesen, Lone Graff Stensballe, Gitte Thybo Pihl, Jesper Kjærgaard, Nina Marie Birk, Thomas Nørrelykke Nissen, Aksel Karl Georg Jensen, Peter Aaby, Annette Wind Olesen, Dorthe Lisbeth Jeppesen, Christine Stabell Benn, Poul Erik Kofoed

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Background: Recurrent wheeze (RW) is frequent in childhood. Studies have suggested that BCG vaccination can have nonspecific effects, reducing general nontuberculosis morbidity, including respiratory tract infections and atopic diseases. The mechanisms behind these nonspecific effects of BCG are not fully understood, but a shift from a TH2 to a TH1 response has been suggested as a possible explanation. Objective: We hypothesized that BCG at birth would reduce the cumulative incidence of RW during the first year of life. Methods: The Danish Calmette Study is a multicenter randomized trial conducted from 2012-2015 at 3 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 of less than 32 weeks, birth weight of less than 1000 g, known immunodeficiency, or no Danish-speaking parent. Information was collected through telephone interviews and clinical examinations at 3 and 13 months of age; data collectors were blind to randomization group. RW was defined in several ways, with the main definition being physician-diagnosed and medically treated RW up to 13 months of age. Results: By 13 months, 211 (10.0%) of 2100 children in the BCG group and 195 (9.4%) of 2071 children in the control group had received a diagnosis of RW from a medical doctor and received antiasthma treatment (relative risk, 1.07; 95% CI, 0.89-1.28). Supplementary analyses were made, including an analysis of baseline risk factors for development of RW. Conclusion: Neonatal BCG had no effect on the development of RW before 13 months of age.

TidsskriftJournal of Allergy and Clinical Immunology
Udgave nummer6
Sider (fra-til)1616-1621.e3
StatusUdgivet - dec. 2017
Udgivet eksterntJa