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

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.