Elsevier

Contemporary Clinical Trials

Volume 42, May 2015, Pages 213-218
Contemporary Clinical Trials

Bacillus Calmette-Guérin immunisation at birth and morbidity among Danish children: A prospective, randomised, clinical trial

https://doi.org/10.1016/j.cct.2015.04.006Get rights and content
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Abstract

Background

Studies from low-income countries report positive non-specific effects of early Bacillus Calmette-Guérin (BCG) immunisation on childhood health and survival. Neonatal immunisation with BCG may prime the immune system and offer partial protection against other infectious and possibly allergic diseases. The potential clinical value of these non-specific effects has not yet been examined in a large randomised trial in high-income countries.

Methods

The Danish Calmette Study is a multicentre randomised clinical trial conducted between October 2012 and November 2015. Within the first 7 days of life, infants were randomly assigned to intra-dermal vaccination with BCG or no intervention. At 3 and 13 months of age structured telephone interviews and clinical examinations of the children were conducted. In a subgroup of children blood samples were drawn and stool samples collected at age 4 days, 3 and 13 months. Thymus index was assessed by ultrasound in a subgroup at randomisation and at 3 months. The primary study outcome is hospitalisation within the first 15 months of life as assessed in Danish health registers. Secondary outcomes include infectious disease hospitalisations, wheezing, eczema, use of prescribed medication, growth, development, thymus index, T- and B-cell subpopulations assessed by flow cytometry, in vitro cytokine responses and specific antibody responses to other vaccines. Adverse reactions were registered.

Discussion

With participation of 4184 families and more than 93% adherence to clinical follow-up at 3 and 13 months, this randomised clinical trial has the potential to create evidence regarding non-specific effects of BCG vaccination in a high-income setting.

Abbreviations

ASQ
Ages and Stages Questionnaire
BCG
Bacillus Calmette-Guérin
C. alb
Candida albicans
cm
centimetre
CPR
Central Person Register
DSMB
Data Safety and Monitoring Board
E. coli
Escherichia coli
e-crf
electronic case report form
g
grams
IgE
immunoglobulin E
IFN-γ
interferon gamma
IL
interleukin
LPS
lipopolysaccharide
MMR
measles, mumps, rubella
Pentavalent vaccine
vaccine against diphtheria, tetanus, Bordetella pertussis, polio and Haemophilus influenza type B
PHA
phytohaemagglutanin
Pneumococcal conjugate vaccine
13-valent vaccine against Streptococcus pneumoniae
SCORAD
scoring atopic dermatitis
SSI
Statens Serum Institut
S. pneu
Streptococcus pneumoniae
Tc
T-cytotoxic cells
Th
T-helper-cell
TNF-α
tumor necrosis factor alpha

Keywords

Bacillus Calmette-Guérin
BCG vaccination
Children
Heterologous immunity
Non-specific effects of vaccines
Randomised clinical trial

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