Thimerosal-Autism Link Discounted in RhIg Study

COLUMBIA, Mo., May 16 -- Prenatal exposure to thimerosal in Rh immunoglobulin (RhIg) does not increase a child's risk for an autism spectrum disorder, said investigators here.

Compared with women in the general population, mothers of children with autism were no more likely to be Rh negative, to have received RhIg preserved with thimerosal during pregnancy, or to have had pregnancies complicated by Rh incompatibility, reported Judith Miles, M.D., Ph.D., and Nicole Takahashi, online in the American Journal of Medical Genetics.

"This study adds to the evidence that there is no casual association between thimerosal and childhood autism," said Dr. Miles, a professor of pediatrics and pathology at the University of Missouri, who also holds an endowed chair in autism. "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."

Thimerosal, which is 49.6% ethylmercury, was included as a preservative in RhIg and in pediatric vaccines manufactured in the United States until 2001.

Because an increase in autism spectrum diagnoses during the 1990s in the U.S. coincided with the introduction of five pediatric vaccines, some investigators and concerned parents have questioned whether the preservative could be to blame.

The vast majority of studies of the putative association have consistently failed to find evidence of a link between thimerosal-preserved vaccines and autism spectrum disorders, the authors noted.

"We hypothesized that if the increased prevalence of autism spectrum disorders were due to exposure of children to ethylmercury in doses received with childhood immunizations, exposure at 28 weeks gestation would pose an even greater risk based on increased neural vulnerability early in development;" they wrote, "and consequently mothers of children with autism would be more likely to be Rh negative and to have received RhIg with thimerosal during pregnancy."

To determine whether prenatal exposure to thimerosal -- via RhIg delivered to prevent erythroblastosis fetalis or other Rh incompatibility syndromes -- could be linked to autism spectrum disorders, the researchers conducted a study of families of children with one of the disorders who were enrolled in their university's autism clinic.

A total of 305 mothers of children with either an autistic disorder, Asperger's syndrome, or pervasive developmental disorder were interviewed by telephone and asked a brief set of questions about their Rh status and whether they had received RhIg during their pregnancies. Positive responses were confirmed by record review.

The authors identified a total of 214 mothers of 230 children diagnosed with an autism spectrum disorder. Thirty-three of the mothers (15.4%) were Rh negative, which is identical to the reported occurrence rate among mothers of children with sporadic genetic disorders (P=0.99, odds ratio 1.000, 95% confidence interval 0.47-2.16). The rate of Rh negativity was also similar to that of the general population of University of Missouri Hospital patients and regional blood donors, the authors noted.

Of the 33 Rh negative mothers, 29 (88%) had received RhIg during their pregnancy. Of the four who did not receive it, one had no prenatal care and two were not offered RhIg, In the fourth mother's case, the father was known to be Rh negative too.

The authors found that prenatal exposure to RhIg was no higher for children with autism than for other children, and that their mothers were no more likely than the general population to have Rh incompatibility during their pregnancies.

When the authors considered whether Rh status or prenatal exposure to thimerosal might be associated with a specific subset of patients with an autism spectrum disorder, they found no statistically significant differences for any of the variables in association with either a specific diagnosis, IQ, gender, essential versus complex phenotype, dysmorphology status, head size, regressive versus early onset autism spectrum disorder, multiplex versus singleton births, or birth order (because of the higher risk for Rh sensitization in subsequent pregnancies).

"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," Dr. Miles said.

The authors noted that the primary limitation of the study is the relatively small number of subjects, especially those who were Rh negative and received ante partum RhIg that contained thimerosal. "It is however the largest study reported and demonstrates how ascertainment biases and recall reports can mislead," they said.

An additional constraint, they acknowledged, is the small age matched control population without autism spectrum disorder.