No Link Between Thimerosal, in Vaccines and Neuropsychological Harm

ATLANTA, Sept. 26 -- Children who were given thimerosal-containing vaccines or Rh globulins a decade ago showed no causal decline in neuropsychological outcomes by ages seven to 10, CDC researchers here found.

These findings suggested that the early exposure to thimerosal, an ethylmercury-containing preservative in vaccines, does not reduce neuropsychological functioning, William W. Thompson, Ph.D., of the CDC, and colleagues, reported in the Sept. 27 issue of the New England Journal of Medicine.

Among 42 neuropsychological tests assessed, only a few significant associations of any kind were identified, none important, the investigators found. The associations were small. Some were positive and some negative.

The findings came from a study of 1,047 children, seven to 10 years old, from four HMOs that participate in the CDC's Vaccine Safety Datalink.

Birthdates ranged from January 1993 through March 1997. The children were given standardized tests assessing 42 neuropsychological outcomes. However, autism-spectrum disorders were not assessed.

Exposure to mercury from thimerosal was determined from computerized immunization records, medical records, personal immunization records, and parent interviews.

The researchers assessed the association between current neuropsychological performance and exposure to mercury during the prenatal period, the neonatal period (birth to 28 days), and the first seven months of life.

The sources of prenatal exposure were flu vaccine, tetanus toxoid, hepatitis B vaccine, and thimerosal-containing Rh globulins.

Among the 42 neuropsychological outcomes, only a few significant associations with exposure to mercury-containing thimerosal were detected. These were small and almost equally divided between positive and negative effects, the researchers said.

For example, higher prenatal mercury exposure was associated with better performance on one measure of language and poorer performance on one measure of attention and executive functioning.

Increasing levels of mercury exposure from birth to seven months were associated with better performance on one measure of fine motor coordination and on one measure of attention and executive functioning.

Increasing mercury exposure from birth to 28 days was associated with poorer performance on one measure of speech articulation and better performance on one measure of fine motor coordination.

Tests of the interactions of mercury exposure from antibiotic use in the first seven months of life showed no consistent results, while tests of an interaction between prenatal and postnatal exposure also revealed no important differences.

Several studies of the effects of prenatal exposure to methyl mercury from fish consumption have shown certain negative associations, the researchers said.

However, they said that using methyl mercury as a referent for assessment of exposure to ethyl mercury from thimerosal is questionable, because the half-life of ethyl mercury in the blood is half that of methyl mercury.

Study limitations included the fact that a majority of the selected families declined to participate or could not be located so that the findings may have been influenced by selection bias.

In addition, they said, they were unable to control for interventions, such as speech therapy. Furthermore, information available for some potential confounding factors, such as family income, was imprecise.

Finally, the researchers wrote that the study did not examine the possible association between autism and exposure to mercury from vaccines and immune globulins.

The overall pattern of this study suggests that any significant associations may have been chance findings stemming from the large number of statistical tests performed, they concluded.

In an accompanying Perspective, Paul A. Offit, M.D., of Children's Hospital in Philadelphia, wrote that by choosing not to vaccinate children, parents elevate a now disproved risk above the real risk of being hospitalized or dying of influenza or other infection.

In recounting earlier thimerosal issues, he wrote that after much wrangling, on July 9, 1999, the CDC and the American Academy of Pediatrics asked pharmaceutical companies to remove thimerosal from vaccines as soon as possible and in the interim asked physicians to delay the birth dose of hepatitis B vaccine for children not at risk.

"The current levels of thimerosal will not hurt children," the Academy said, but "reducing these levels will make safe vaccines even safer." Critics wondered, Dr. Offit said, how removing something that had not been found unsafe could make vaccines safer, while many parents reasoned that thimerosal was targeted because it was harmful.

Clinicians were also confused, and some unprotected children died as a result of overwhelming infection.

Then beginning in 2000, parents founded several advocacy groups based on the belief that thimerosal had caused their children's autism, and a "cottage industry of charlatans offering false hope, partly in the form of mercury-chelating agents, was born," Dr. Offit said.

Despite several years of reassuring studies finding no association with autism or other neuropsychological outcomes, the thimerosal controversy continues to be emotionally charged. Thimerosal will probably be removed from flu vaccines and the controversy will settle down, Dr. Offit wrote.

"But the thimerosal controversy should stand as a cautionary tale of how not to communicate theoretical risks to the public," he wrote. Otherwise, he said, "the lesson inherent in the collateral damage caused by its precipitous removal will remain unlearned."

In a second Perspective, Stephen D. Sugarman, J.D., of the University of California at Berkeley, reviewed the legal battles now being waged over vaccines and autism and did not see an end to the litigation.

Although most experts have concluded that there is no proof of a causal tie between autism and thimerosal or the MMR vaccine, he wrote, some doctors and scientists, some groups representing families with autistic children, and many parents fervently believe there is a connection.

Not only do these families have support groups and organized lawyers behind them, but they also have the backing of several prominent senators and congressional representatives.

Whatever the outcome of the current lawsuits in the U.S. and Britain, it is unlikely that the battles over vaccines and autism will end, he concluded.

Dr. Thompson reported being a former employee of Merck. Co-authors reported receiving consulting fees, lecture fees, and other forms or remuneration from Merck, Sanofi Pasteur, GlaxoSmithKline, MedImmune, Wyeth, Novartis, Abbott, and Aventis.

Co-author Lisa A. Jackson, M.D., reported serving as a consultant to the FDA Vaccines and Related Biological Products Advisory Committee; Tracy A. Lieu, M.D., reported serving as a consultant to the CDC Advisory Committee on Immunization Practices.

Dr. Offit, author of an accompanying Perspective, reported serving on the scientific advisory board of Merck and being the co-inventor of the bovine-human reassortant rotavirus vaccine RotaTeq, on which he holds a patent.

Mr. Sugarman, author of the other Perspective, reported no financial conflicts.