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Neonatal BCG vaccination has no effect on recurrent wheeze in the first year of life: A randomized clinical trial
Lisbeth Marianne Thøstesen1, Lone Graff Stensballe2, Gitte Thybo Pihl1
1Department of Pediatrics, Kolding Hospital, and the Institute of Regional Health Research, University of Southern Denmark, Kolding, Denmark.
Insights
Neonatal BCG vaccination did not reduce recurrent wheeze (RW) in infants. This study found no significant difference in RW incidence between infants who received the BCG vaccine at birth and those who did not.
Area of Science:
- Immunology
- Pediatrics
- Public Health
Background:
- Recurrent wheeze (RW) is a common childhood condition.
- Bacillus Calmette-Guérin (BCG) vaccination may offer non-specific benefits, potentially reducing respiratory infections and atopic diseases.
- The immunomodulatory mechanisms of BCG, possibly involving a shift from TH2 to TH1 responses, are not fully elucidated.
Purpose of the Study:
- To investigate the hypothesis that BCG vaccination at birth reduces the cumulative incidence of recurrent wheeze (RW) within the first year of life.
Main Methods:
- A multicenter randomized controlled trial involving 4262 newborns randomized to BCG vaccination or a control group.
- Participants were assessed at 3 and 13 months of age via telephone interviews and clinical examinations.
- Recurrent wheeze was defined as physician-diagnosed and medically treated RW up to 13 months of age.
Main Results:
- By 13 months of age, 10.0% of the BCG group and 9.4% of the control group experienced recurrent wheeze.
- The relative risk of developing RW in the BCG group compared to the control group was 1.07 (95% CI, 0.89-1.28).
- No statistically significant difference in RW incidence was observed between the two groups.
Conclusions:
- Neonatal BCG vaccination demonstrated no effect on the development of recurrent wheeze before 13 months of age.
- Further research may be needed to explore other potential non-specific effects of BCG vaccination in early childhood.
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.
