Lack of a Negative Effect of BCG-Vaccination on Child Psychomotor Development: Results from the Danish Calmette Study - A Randomised Clinical Trial

Jesper Kjærgaard, Lone Graff Stensballe, Nina Marie Birk, Thomas Nørrelykke Nissen, Kim Thestrup Foss, Lisbeth Marianne Thøstesen, Gitte Thybo Pihl, Andreas Andersen, Poul-Erik Kofoed, Ole Pryds, Gorm Greisen, Jesper Kjærgaard, Lone Graff Stensballe, Nina Marie Birk, Thomas Nørrelykke Nissen, Kim Thestrup Foss, Lisbeth Marianne Thøstesen, Gitte Thybo Pihl, Andreas Andersen, Poul-Erik Kofoed, Ole Pryds, Gorm Greisen

Abstract

Objectives: To assess the non-specific effect of Bacillus Calmette-Guérin (BCG) vaccination at birth on psychomotor development.

Design: This is a pre-specified secondary outcome from a randomised, clinical trial.

Setting: Maternity units and paediatric wards at three university hospitals in Denmark.

Participants: Children born at gestational age (GA) 32 weeks and above. All women planning to give birth at the three sites were invited during the recruitment period. Out of 4262 randomised children, 144 were premature (GA < 37 weeks). There were 2129 children (71 premature) randomised to BCG and 2133 randomised (73 premature) to the control group.

Interventions: BCG vaccination 0.05 ml was given intradermally in the upper left arm at the hospital within seven days of birth. Children in the control group did not receive any intervention. Parents were not blinded to allocation.

Main outcome measures: Psychomotor development measured using Ages and Stages Questionnaire (ASQ) completed by the parents at 12 months. Additionally, parents of premature children (gestational age < 37 weeks) completed an ASQ at 6 and 22 months. Developmental assessment was available for 3453/4262 (81%).

Results: The mean difference in ASQ score at 12 months adjusted for age and prematurity was -0.7 points (BCG vs. control, 95% confidence interval; -3.7 to 2.4), p = 0.67, corresponding to an effect size of Cohen's d = -0.015 (-0.082 to 0.052). The mean difference in ASQ score for premature children at 22 months was -7.8 points (-20.6 to 5.0, p = 0.23), d = -0.23 (-0.62 to 0.15).

Conclusions: A negative non-specific effect of BCG vaccination at birth on psychomotor development was excluded in term children.

Trial registration: ClinicalTrials.gov NCT01694108.

Conflict of interest statement

Competing Interests: Andreas Andersen, statistician, is associated with the Statens Serum Institut (SSI). SSI produces the BCG vaccine used in the authors' study. The vaccines used in this study were bought at standard prices and SSI had no role in designing, conducting, analyzing or funding the study.

Figures

Fig 1. Participant flowchart.
Fig 1. Participant flowchart.
Fig 2. Box-plots of ASQ sub-domain and…
Fig 2. Box-plots of ASQ sub-domain and total scores at 6, 12, 22 months for premature children.
ASQ: Ages and stages questionnaire. Coms: Communication score. Fms: Fine motor score. Gms: Gross motor score. Pss: Problem solving score. Psds: Personal and social development score. BCG: Bacillus Calmette-Guèrin vaccine.

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