No link found between thimerosal, neurodevelopmental disorders

November 2001

WASHINGTON, D.C. — An advisory committee of the Institute of Medicine (IOM) has concluded that there is no evidence to support a link between thimerosal-containing vaccines and neurodevelopmental disorders. However, a biological plausibility could not be ruled out.

In 1999, the FDA called for removal of the preservative thimerosal from Haemophilus influenzae type b (Hib), diphtheria-tetanus-acellular pertussis (DTaP) and hepatitis B (HepB) vaccines for children to reduce childhood exposure to mercury. Since children who adhered to the complete immunization schedule may have been exposed to levels of mercury above some federal breakpoints, an IOM committee was convened to examine the causal link and biological plausibility of neurodevelopmental disorders as a result of thimerosal exposure.

The FDA decision in 1999, however, was not an admission that thimerosal is dangerous. Rather, it was intended to reduce overall mercury exposure in children.

“Neither at that time, nor today, does any data exist to prove that thimerosal is dangerous at the levels present in vaccines,” said Marie McCormick, MD, ScD, chair of the IOM review panel, during a recent press conference.

Thimerosal is still used in some biological products to prevent bacterial growth, most notably influenza vaccine and some nasal sprays. Still, the advisory committee did not recommend removing the preservative from these products because of limited data on thimerosal’s contribution to neurodevelopmental disorders, a minute biological plausibility and the benefits these products provide.

No proven link

The IOM review looked at available epidemiological, biological and clinical evidence relating to thimerosal and its active ingredient, ethylmercury. The panel also looked at analogous evidence from studies on methylmercury, a close chemical relative of ethylmercury found largely in foods such as fish.

There was only one study directly examining the link between thimerosal and neurodevelopmental disorders. A review of unpublished data from the Vaccine Safety Datalink revealed a small but significant risk for speech delay, language disorders and attention-deficit/hyperactivity disorder (ADHD). However, the report found no clear evidence that thimerosal in trace amounts can cause neurodevelopmental disorders including autism.

“The hypothesis that thimerosal exposure through the recommended childhood immunization schedule causes neurodevelopmental disorders is not supported by clinical or experimental evidence,” said McCormick, who is a professor of maternal and child health at Harvard School of Public Health.

Data were extremely limited regarding the possible link. Available case reports could not definitively define causality, there were no epidemiological studies regarding the link between thimerosal and neurodevelopmental disorders and available studies provided only weak and inconclusive evidence, according to the report. As well, the data did not show a consistent dose relationship.

“Existing epidemiologic evidence is inadequate to either support or reject the causal relationship between thimerosal from vaccines and the neurodevelopmental disorders of autism, ADHD and speech or language delay,” said McCormick.

Biological plausibility

However, a biological plausibility could not be ruled out after a review of the data. Toxicological evidence relating to methylmercury showed that it is toxic to developing nerve systems and ethylmercury in high doses is known to cause renal damage. As well, some children may be predisposed to mercury sensitivity, either genetically or by other factors.

“Although the evidence is indirect and incomplete, and the relationship is not established, it is biologically plausible” that exposure to thimerosal could contribute to neurodevelopmental disorders, said the study.

The panel’s decision not to recommend removal of thimerosal from all products was based on several factors. For one, vaccines provide protection against serious diseases and infections. While the risk of neurodevelopmental disorders is possible, the benefit provided by immunologic products is real.

“The health effects of thimerosal are not known, but the greater risk from diseases is known. The risk of having a vaccine-preventable disease is very real, but the risk of an adverse effect is only a possibility,” said McCormick.

Vaccine manufacturers have already switched to single-dose vials to eliminate the need for thimerosal in developed countries. However, multidose vials are still in use in many poorer nations, and the benefits they provide are significant. If the IOM had mandated removal of all thimerosal from vaccines, it could have a dramatic economic and public health impact for developing nations.

Vaccination

The IOM panel recommended that if thimerosal-free vaccines are available, they are preferred, but if not, thimerosal-containing vaccines are better than no vaccines. As well, the IOM panel said more studies are needed to both see if any children may have been affected by the thimerosal exposure and also to further delineate the risk of neurodevelopmental disorders after thimerosal exposure.

For more information:

• The Institute of Medicine report, “Immunization safety review: thimerosal-containing vaccines and neurodevelopmental disorders” can be obtained from the IOM Web site: www.iom.edu.