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

TY - JOUR

T1 - Lack of a Negative Effect of BCG-Vaccination on Child Psychomotor Development

T2 - Results from the Danish Calmette Study - A Randomised Clinical Trial

AU - Kjærgaard, Jesper

AU - Stensballe, Lone Graff

AU - Birk, Nina Marie

AU - Nissen, Thomas Norrelykke

AU - Foss, Kim Thestrup

AU - Thøstesen, Lisbeth Marianne

AU - Pihl, Gitte Thybo

AU - Andersen, Andreas

AU - Kofoed, Poul-Erik

AU - Pryds, Ole

AU - Greisen, Gorm

PY - 2016/4

Y1 - 2016/4

N2 - 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.

AB - 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.

KW - Adult

KW - BCG Vaccine

KW - Denmark

KW - Female

KW - Humans

KW - Infant

KW - Infant, Newborn

KW - Infant, Premature

KW - Mycobacterium bovis

KW - Psychomotor Performance

KW - Surveys and Questionnaires

KW - Tuberculosis, Pulmonary

KW - Vaccination

KW - Journal Article

KW - Randomized Controlled Trial

KW - Research Support, Non-U.S. Gov't

U2 - 10.1371/journal.pone.0154541

DO - 10.1371/journal.pone.0154541

M3 - Journal article

C2 - 27123570

SN - 1932-6203

VL - 11

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 4

M1 - e0154541

ER -