Lone Graff Stensballe1, Henrik Ravn2,3, Nina Marie Birk4, Jesper Kjærgaard5, Thomas Nørrelykke Nissen4, Gitte Thybo Pihl6, Lisbeth Marianne Thøstesen6, Gorm Greisen7, Dorthe Lisbeth Jeppesen4, Poul-Erik Kofoed6, Ole Pryds4, Signe Sørup2, Peter Aaby8, Christine Stabell Benn3,9. 1. Child and Adolescent Clinic, Juliane Marie Centret, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej, Copenhagen Ø, Denmark. 2. Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Artillerivej, Copenhagen S, Denmark. 3. OPEN, Odense Patient Data Explorative Network, Odense University Hospital/Department of Clinical Research, University of Southern Denmark. 4. Department of Pediatrics, Copenhagen University Hospital, Hvidovre, Kettegaard Allé, Hvidovre, Denmark. 5. Research Unit Womens' and Childrens' Health, Child and Adolescent Clinic, Juliane Marie Centret, Rigshospitalet, Copenhagen University Hospital, Copenhagen Ø, Denmark. 6. Department of Pediatrics, Kolding Hospital, Skovvangen, Kolding and Institute of Regional Health Research, University of Southern Denmark. 7. Neonatal Department, Juliane Marie Centret, Rigshospitalet, Copenhagen University Hospital, Copenhagen Ø, Denmark. 8. Bandim Health Project, Statens Serum Institut, Copenhagen S, Denmark. 9. Research Center for Vitamins and Vaccines (CVIVA), Statens Serum Institut, Copenhagen S, Denmark.
Abstract
BACKGROUND: The bacillus Calmette-Guérin (BCG) vaccine against tuberculosis might reduce the non-tuberculosis-related child mortality rate in low-income settings. We tested the hypothesis that BCG vaccination at birth would reduce early childhood hospitalization for infection in Denmark, a high-income setting. Hospitalization for infection was a secondary outcome in a randomized trial with the primary aim to estimate the potential non-specific effects of BCG vaccination at birth on all-cause hospitalization. METHODS: A total of 4262 children included in the Danish Calmette Study were assigned randomly to either receive the BCG vaccine or not and were followed through the Danish National Patient Register. The outcome was number of hospitalizations for infection until the age of 15 months. Data were analyzed by Cox regression in intention-to-treat (ITT) and per-protocol (PP) analyses. RESULTS: In the ITT analysis, we observed 588 hospitalizations for infection (mean, 0.28 hospitalization per child) among the 2129 children allocated to receive the BCG vaccine and 595 hospitalizations for infection (mean, 0.28 hospitalization per child) among the 2133 children allocated to the control group (hazard ratio [HR], 0.99 [95% confidence interval (CI), 0.85-1.15]). The PP analysis yielded an HR of 1.00 (95% CI, 0.86-1.16).Predefined interaction ITT analyses showed that among 740 children with a BCG-vaccinated mother, the HR for BCG-vaccinated children was 0.65 (95% CI, 0.45-0.94); the HR for children who had a non-BCG-vaccinated mother was 1.10 (95% CI, 0.93-1.29) (P = .01, test of no interaction). Cesarean delivery modified the effect of BCG vaccination (HRs, 0.73 [95% CI, 0.54-0.99] in children born by cesarean section vs 1.10 [95% CI, 0.92-1.30] in other children; P = .02). When the outcome was defined as time to first hospitalization, the HR for premature children after BCG vaccination was 1.81 (95% CI, 0.95-3.43), whereas the HR was 0.94 (95% CI, 0.82-1.08) for children born at term (P = .05). CONCLUSION:BCG vaccination did not affect the rate of hospitalization for infection up to the age of 15 months in Danish children. In future studies, the role of maternal BCG-vaccination, premature birth, and cesarean delivery needs further exploration.
RCT Entities:
BACKGROUND: The bacillus Calmette-Guérin (BCG) vaccine against tuberculosis might reduce the non-tuberculosis-related child mortality rate in low-income settings. We tested the hypothesis that BCG vaccination at birth would reduce early childhood hospitalization for infection in Denmark, a high-income setting. Hospitalization for infection was a secondary outcome in a randomized trial with the primary aim to estimate the potential non-specific effects of BCG vaccination at birth on all-cause hospitalization. METHODS: A total of 4262 children included in the Danish Calmette Study were assigned randomly to either receive the BCG vaccine or not and were followed through the Danish National Patient Register. The outcome was number of hospitalizations for infection until the age of 15 months. Data were analyzed by Cox regression in intention-to-treat (ITT) and per-protocol (PP) analyses. RESULTS: In the ITT analysis, we observed 588 hospitalizations for infection (mean, 0.28 hospitalization per child) among the 2129 children allocated to receive the BCG vaccine and 595 hospitalizations for infection (mean, 0.28 hospitalization per child) among the 2133 children allocated to the control group (hazard ratio [HR], 0.99 [95% confidence interval (CI), 0.85-1.15]). The PP analysis yielded an HR of 1.00 (95% CI, 0.86-1.16).Predefined interaction ITT analyses showed that among 740 children with a BCG-vaccinated mother, the HR for BCG-vaccinated children was 0.65 (95% CI, 0.45-0.94); the HR for children who had a non-BCG-vaccinated mother was 1.10 (95% CI, 0.93-1.29) (P = .01, test of no interaction). Cesarean delivery modified the effect of BCG vaccination (HRs, 0.73 [95% CI, 0.54-0.99] in children born by cesarean section vs 1.10 [95% CI, 0.92-1.30] in other children; P = .02). When the outcome was defined as time to first hospitalization, the HR for premature children after BCG vaccination was 1.81 (95% CI, 0.95-3.43), whereas the HR was 0.94 (95% CI, 0.82-1.08) for children born at term (P = .05). CONCLUSION:BCG vaccination did not affect the rate of hospitalization for infection up to the age of 15 months in Danish children. In future studies, the role of maternal BCG-vaccination, premature birth, and cesarean delivery needs further exploration.
Authors: Valerie Acm Koeken; L Charlotte J de Bree; Vera P Mourits; Simone Jcfm Moorlag; Jona Walk; Branko Cirovic; Rob Jw Arts; Martin Jaeger; Helga Dijkstra; Heidi Lemmers; Leo Ab Joosten; Christine S Benn; Reinout van Crevel; Mihai G Netea Journal: J Clin Invest Date: 2020-10-01 Impact factor: 14.808
Authors: Bridget Freyne; Nicole L Messina; Susan Donath; Susie Germano; Rhian Bonnici; Kaya Gardiner; Dan Casalaz; Roy M Robins-Browne; Mihai G Netea; Katie L Flanagan; Toby Kollmann; Nigel Curtis Journal: J Infect Dis Date: 2020-06-11 Impact factor: 5.226
Authors: Wei-Ju Su; Chia-Hsuin Chang; Jiun-Ling Wang; Shu-Fong Chen; Chin-Hui Yang Journal: Int J Environ Res Public Health Date: 2021-04-18 Impact factor: 3.390