PEDIATRICS Vol. 114 No. 3 September 2004, pp. 793-804 (doi:10.1542/peds.2004-0434)
Thimerosal-Containing Vaccines and Autistic Spectrum Disorder: A Critical Review of Published Original Data
* Department of Pediatrics, Children's Hospital and University of Colorado Health Sciences Center, Denver, Colorado
National Immunization Program, Centers for Disease Control and Prevention, Atlanta, Georgia
Objective. The issue of thimerosal-containing vaccines as a possible cause of autistic spectrum disorders (ASD) and neurodevelopmental disorders (NDDs) has been a controversial topic since 1999. Although most practitioners are familiar with the controversy, many are not familiar with the type or quality of evidence in published articles that have addressed this issue. To assess the quality of evidence assessing a potential association between thimerosal-containing vaccines and autism and evaluate whether that evidence suggests accepting or rejecting the hypothesis, we systematically reviewed published articles that report original data pertinent to the potential association between thimerosal-containing vaccines and ASD/NDDs.
Methods. Articles for analysis were identified in the National Library of Medicine's Medline database using a PubMed search of the English-language literature for articles published between 1966 and 2004, using keywords thimerosal, thiomersal, mercury, methylmercury, or ethylmercury alone and combined with keywords autistic disorder, autistic spectrum disorder, and neurodevelopment. In addition, we used the "related links" option in PubMed and reviewed the reference sections in the identified articles. All original articles that evaluated an association between thimerosal-containing vaccines and ASD/NDDs or pharmacokinetics of ethylmercury in vaccines were included.
Results. Twelve publications that met the selection criteria were identified by the literature search: 10 epidemiologic studies and 2 pharmacokinetic studies of ethylmercury. The design and quality of the studies showed significant variation. The preponderance of epidemiologic evidence does not support an association between thimerosal-containing vaccines and ASD. Epidemiologic studies that support an association are of poor quality and cannot be interpreted. Pharmacokinetic studies suggest that the half-life of ethylmercury is significantly shorter when compared with methylmercury.
Conclusions. Studies do not demonstrate a link between thimerosal-containing vaccines and ASD, and the pharmacokinetics of ethylmercury make such an association less likely. Epidemiologic studies that support a link demonstrated significant design flaws that invalidate their conclusions. Evidence does not support a change in the standard of practice with regard to administration of thimerosal-containing vaccines in areas of the world where they are used.
Key Words: thimerosal • thiomersal • mercury • vaccine • methylmercury • ethylmercury • autism • autistic disorder • autistic spectrum disorder • developmental disorder • neurodevelopmental disorder
Abbreviations: ASD, autistic spectrum disorders • MMR, measles, mumps, rubella • EPA, Environmental Protection Agency • FDA, Food and Drug Administration • NDD, neurodevelopmental disorder • VAERS, Vaccine Adverse Events Reporting System • AE, adverse event • DTaP, diphtheria, tetanus, acellular pertussis • CI, confidence interval • CDC, Centers for Disease Control and Prevention • DTP, diphtheria, tetanus, whole-cell pertussis • HMO, health maintenance organization • RR, relative risk • ADD, attention-deficit disorder • GPRD, General Practice Research Database • DT, diphtheria, tetanus
Accepted May 19, 2004.
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