A new study published yesterday (Monday) in the journal Pediatrics provides more evidence against any link between thimerosal (a mercury-based preservative in some vaccines) and autism or other neurological disorders. This study adds to the large and growing body of scientific evidence for the safety of vaccines, and contradicting the claims of the anti-vaccine movement that vaccines cause autism.

The study is a bit fortuitous in that it was not originally designed to probe this question. Rather, this was a safety and efficacy study of the acellular pertussis vaccine conducted in Italy between 1992 and 1993. But it created a cohort of children who were carefully screened and monitored, and randomized to different exposures to thimerosal. This allowed the researchers to go back 10 years later to survey and examine the children for neurological disorders.

Here are the methods:

Children who were enrolled in an efficacy trial of pertussis vaccines in 1992–1993 were contacted in 2003. Two groups of children were identified, according to thimerosal content in vaccines assigned randomly in the first year of life (cumulative ethylmercury intake of 62.5 or 137.5 µg), and were compared with respect to neuropsychological outcomes. Eleven standardized neuropsychological tests, for a total of 24 outcomes, were administered to children during school hours. Mean scores of neuropsychological tests in the domains of memory and learning, attention, executive functions, visuospatial functions, language, and motor skills were compared according to thimerosal exposure and gender. Standard regression coefficients obtained through multivariate linear regression analyses were used as a measure of effect.

The results – there was only one case of autism in the entire study, and that was in the group that received the lower dose of thimerosal. Of the 24 neuropsychological tests, only two were significantly worse in the higher dose thimerosal group:

Girls with higher thimerosal intake had lower mean scores in the finger-tapping test with the dominant hand and in the Boston Naming Test.

The differences were clinically small, even though they were statistically significant. However, by chance alone (with the statistics used) 4 outcomes on average should have varied significantly, therefore the fact that 2 outcomes were significant is almost certainly due to chance alone. Further, these same measures were not different for boys or the groups as a whole, only when girls are considered seperately, which further suggests it is statistical chance.

And finally, a previous study by the CDC that also looked at a large number of neurological measures also found a few statistical outliers – but they were different outcomes. For example, the previous CDC study showed that motor tics were increased in the thimerosal exposure group, while this study shows no difference in motor tics but does show a decrease in finger tapping. This is all consistent with statistical noise – not a real effect.

The study authors conclude:

No study conducted to date has been able to provide conclusive evidence of an effect of thimerosal on neuropsychological development. Final judgments regarding this association must rely on the entire body of results from studies conducted in different settings and with different levels of validity and on the coherence of results. The lack of consistency among the results of our study and other available studies suggests that an association between thimerosal exposure through vaccination in infancy and neuropsychological deficits is unlikely or clinically negligible. Additional data from populations with wider ranges of exposure to thimerosal and additional neuropsychological assessments at older ages may help to clarify the issue of potential associations between thimerosal and neurodevelopmental outcomes.

This is appropriately conservative prose for a technical paper, but even so the conclusion is solid – any association between thimerosal and neurological disorders is “unlikely or clinically negligible.”

Of course, no one study by itself is definitive, especially in establishing the absence of a correlation. But this new study adds to an already large body of evidence, and therefore raises our confidence further that thimerosal in vaccines did not cause autism or other neurological disorders.

The authors are also candid about the strengths and weaknesses of the study. Anti-vaccinationists have been calling for years for a randomized study with and without vaccines – because that is the one type of data that was not available. It is unethical to randomize a patient not to receive a standard therapy.

This study, however, is close because subjects were randomized to two very different doses of thimerosal.

Another likely source of criticism is that the total cumulative dose of ethylmercury in the higher exposure group was 137.5 µg and that this might be below the threshold of toxicity, and therefore says nothing about the risks of higher exposures. This is true, but not likely to be relevant to the thimerosal question. In the US thimerosal exposure was about 75 µg in 1989 and peaked in 1997 at 187.5 µg cumulative exposure through the routine childhood schedule.

It does not seem plausible that the increase in µg of ethylmercury from 75 to 187.5 resulted in a dramatic increase in autism, but the difference between 62.5 and 137.5 in this study was sub-threshold. Also, I have to point out that since 2000 the use of thimersal in the US has decreased and now there are less than 3 µg in the childhood schedule and the rate of increase in autism diagnoses has not decreased even six years later.

Conclusion

This study adds to the consensus of existing evidence for a lack of association between thimerosal in vaccines and autism or other neurological disorders. However, since the anti-vaccination movement is largely ideological and disconnected from the scientific evidence I do not anticipate that this will end the controversy.