A cross-sectional study of the relationship between infant Thimerosal-containing hepatitis B vaccine exposure and attention-deficit/hyperactivity disorder

J Trace Elem Med Biol. 2018 Mar;46:1-9. doi: 10.1016/j.jtemb.2017.11.001. Epub 2017 Nov 8.


Attention-deficit/hyperactivity disorder (ADHD) is characterized by a marked pattern of inattention and/or hyperactivity-impulsivity that is inconsistent with developmental level and interferes with normal functioning in at least two settings. This study evaluated the hypothesis that infant Thimerosal-containing hepatitis B vaccine (T-HepB) exposure would increase the risk of an ADHD diagnosis. This cross-sectional study examined 4393 persons between 13 and 19 years of age from the combined 1999-2004 National Health and Nutritional Examination Survey (NHANES) by analyzing demographic, immunization, socioeconomic, and health-related variables using the SAS system. Three doses of T-HepB exposure in comparison to no exposure significantly increased the risk of an ADHD diagnosis using logistic regression (adjusted odds ratio=1.980), linear regression (adjusted beta-coefficient=0.04747), Spearman's rank (Rho=0.04807), and 2×2 contingency table (rate ratio=1.8353) statistical modeling even when considering other covariates such as gender, race, and socioeconomic status. Current health status outcomes selected on an a priori basis to not be biologically plausibly linked to T-HepB exposure showed no relationship with T-HepB. The observed study results are biologically plausible and supported by numerous previous epidemiological studies, but because the NHANES data is collected on a cross-sectional basis, it is not possible to ascribe a direct cause-effect relationship between exposure to T-HepB and an ADHD diagnosis. During the decade from 1991 to 2001 that infants were routinely exposed to T-HepB in the United States (US), an estimated 1.3-2.5 million children were diagnosed with ADHD with excess lifetime costs estimated at US $350-$660 billion as a consequence of T-HepB. Although Thimerosal use in the HepB in the US has been discontinued, Thimerosal remains in the HepB in developing countries. Routine vaccination is an important public health tool to prevent infectious diseases, but every effort should be made to eliminate Thimerosal exposure.

Keywords: ADD; Attention deficit disorder; Ethylmercury; Mercury; Merthiolate; NHANES; Thiomersal.

MeSH terms

  • Adolescent
  • Attention Deficit Disorder with Hyperactivity / etiology*
  • Cross-Sectional Studies
  • Female
  • Hepatitis B Vaccines / adverse effects*
  • Humans
  • Infant
  • Male
  • Models, Statistical
  • Nutrition Surveys
  • Preservatives, Pharmaceutical / adverse effects*
  • Risk Factors
  • Thimerosal / adverse effects*
  • United States
  • Vaccination
  • Young Adult


  • Hepatitis B Vaccines
  • Preservatives, Pharmaceutical
  • Thimerosal