Lack of association between Rh status, Rh immune globulin in pregnancy and autism

The increase in the number of diagnosed cases of autism in recent years has sparked concern that environmental toxins may cause this complex disorder.

However, a new University of Missouri-Columbia study concludes that exposure to Rh immune globulin preserved with mercury-containing thimerosal before birth was no higher for children with autism.

"This study adds to the evidence that there is no casual association between thimerosal and childhood autism," said Judith Miles, who is the William S. Thomson Endowed Chair of Autism and professor of pediatrics and pathology in the MU School of Medicine. "We conclude that there is no indication that pregnancies resulting in children with autism were more likely to be complicated by Rh immune globulin/thimerosal exposure."

The study investigated thimerosal exposure during pregnancies that resulted in the birth of a child subsequently diagnosed with autism. Although experts anticipate that autism will be the first behavioral/psychiatric disorder for which major genes will be identified, there is still fierce debate that thimerosal, a preservative commonly used in vaccines and is almost 50 percent ethylmercury, is responsible for the rise in the disorder. Rh negative women are routinely treated with Rh immune globulin (RhIg) during the third trimester to prevent hemolytic disease, in which the mother's immune system attacks fetal blood cells. Like many vaccines, RhIg manufactured in the United States contained thimerosal prior to 2001. Since young fetal brains are more susceptible to neurotoxic effects, researchers led by Miles, of the MU Thompson Center for Autism and Neurodevelopmental Disorders, assessed Rh status and thimerosal exposure of mothers of children with autism.

The study included 214 mothers of 230 children diagnosed with an autism spectrum disorder. Rh status, RhIg with thimerosal exposure and Rh incompatibility (in which the mother's Rh status is different than the fetus's) were established by reviewing medical records. The results showed that in children with autism, Rh negative status was no higher in their mothers than in the general population, that exposure to RhIg (preserved with thimerosal) before birth was no higher and that pregnancies were not more likely to be Rh incompatible.

"We hope this report of no association between autism, Rh negativity and thimerosal exposure during pregnancy will offset some of the decreased compliance with immunization recommendations which is known to increase morbidity and mortality from childhood infectious diseases," Miles said.

Autism diagnoses have increased significantly during the past two decades, which coincides temporally with the addition of five pediatric vaccines to the immunization schedule, exposing children to increasing doses of ethylmercury, a known toxin. Though the vast majority of studies indicate no association between vaccines and autism, the FDA, CDC and American Academy of Pediatrics recommended that thimerosal be removed from all routinely recommended early childhood vaccines; this was accomplished by 2002.

Miles points out that even though RhIg and childhood vaccines are now free of thimerosal in the United States, it is important to analyze questions of safety since thimerosal continues to be used in many places around the world to preserve vaccines to help make them affordable.

Miles said that few studies have focused on pregnancies of Rh negative mothers who received RhIg during pregnancy, probably because the thimerosal is diluted before reaching the fetus and has been assumed to be innocuous. Nevertheless, there is a concern that even very small doses delivered when the brain is especially sensitive can be toxic. Numerous Internet sites and one research study assert that RhIg causes autism and that a high percentage of mothers of children with autism are Rh negative, neither of which was shown to be true in the current study. In addition, a recent study hypothesized that Rh incompatibility itself could disrupt fetal neurodevelopment, thus playing a role in autism, but the current study found no increase in the proportion of Rh incompatibility in mothers of autistic children. In response to the claim that only certain groups of children are at risk, the authors also analyzed specific autism spectrum disorder subgroups and found that none had significant increases in either Rh negativity or thimerosal exposure during pregnancy.

The study "Lack of Association Between Rh Status, Rh Immune Globulin in Pregnancy and Autism" was published in the May 2007 issue of the American Journal of Medical Genetics.