The etiology of autism is not yet clear and the debate continues about whether the increase in prevalence noted in the past few decades is actual or is because of better diagnosis. However, the evidence for a genetic link is accumulating, as is evidence that mercury in vaccines is not behind the increased prevalence.
Because the disease appears in the second or third year of life, the potential association with early childhood vaccines has been the subject of many studies over the past 15–20 years. Children receive many vaccines during the first few years of their lives; until 2002, thimerosal, a preservative that contains ethylmercury, was used as a preservative in routine early childhood vaccines. To a lesser degree, prenatal exposure to Rh immune globulin—which, until 2001 in the United States, contained thimerosal—has also elicited concern. Because organic mercury is a proven developmental neurotoxin, exposure to it in utero or in early childhood has raised concerns.
In utero exposure to mercury in environmental accidents, especially organic mercury, has been associated with brain damage and pediatric diagnoses such as cerebral palsy—but not autism. Some of the most compelling evidence indicating that vaccines containing thimerosal are not a cause of autism was provided in studies that looked at population-based databases of children in Denmark, Sweden, and California.
Although the prevalence of autism increased in all three places from 1985 through the 1990s, the average exposure to vaccines containing mercury increased only in the United States. In Sweden and Denmark, where the use of mercury-containing vaccines began to decrease in the late 1980s and was eliminated by the early 1990s, there was still an increase in the diagnosis of autism.
An important study published last month provides compelling evidence that prenatal exposure to thimerosal in Rh immune globulin is not a likely cause of the increase in autism, either. These results should help allay lingering concerns about exposure to ethylmercury via thimerosal in vaccines and Rh immune globulin.
The new study analyzed records of families that have children with an autism spectrum disorder (ASD), who had been seen at the Thompson Center for Autism and Neurodevelopmental Disorders at the University of Missouri-Columbia, between 2004 and 2006. Of 214 mothers with 230 children diagnosed with ASD between 1995 and 2005, 33 (15.4%) were Rh negative, which was similar to the rates among mothers in control groups. Of these 33 women, 29 (88%) had received Rh immune globulin that contained thimerosal while pregnant.
Based on comparisons with families of children with Down syndrome and other de novo chromosome disorders who came to the university for care, and two other populations—patients blood typed at the hospital in 2005 and 2006, and a population who had donated blood during 2005—the investigators determined that Rh-negative status was not higher among the mothers of children with autism. In addition, the mothers of children with autism were not more likely to have been exposed to antepartum Rh immune globulin containing thimerosal, and were not more likely to have an Rh-negative incompatible pregnancy. These findings were also true for autism subtypes.
The authors concluded that the results “support the consensus that exposure to ethylmercury in thimerosal is not the cause of the increased prevalence of autism” (Am. J. Med. Genet. Part A 2007;143A:1397–407).
Therefore, based on the information currently available, it is fair to say there is no compelling evidence indicating that exposure of the developing brain to mercury, either in the fetus or the developing child, is a cause of autism. And as the authors point out, these findings also have implications for other countries, where multidose vials that contain thimerosal continue to be used.
As for other potential prenatal causes of autism, there have been more case reports of autism in children exposed in utero to valproic acid, isotretinoin, or alcohol than one would expect. But I emphasize that these are case reports and merely associations at this point, not proven causes.
Efforts are underway to further investigate the possible association between prenatal exposure to valproic acid and autism. At the Motherisk Program, a teratogen information service at the Hospital for Sick Children in Toronto, we are following the long-term development of children exposed in utero to valproic acid, which we hope will pick up an association with autism, if such a link exists.