of an association with immunization with MMR and is not clear about immunization with other vaccines.

Autism

The initial literature search identified 32 papers on the relationship between immunizations or vaccines and pervasive developmental disorder (PDD), which includes the diagnoses autistic spectrum disorder, autism, and Asperger’s syndrome. After an initial review, a team of two IOM committee members determined that 12 papers focused on some aspect of the immunization schedule. Three of the papers either addressed only one vaccine or had methodological limitations. The other nine studies examined the association between thimerosal and autism and other neurodevelopmental problems (Andrews et al., 2004; Fombonne et al., 2006; Geier and Geier, 2003, 2004a,b, 2006; Hviid et al., 2003; Madsen et al., 2003; Young et al., 2008). Five of the studies had serious methodological limitations and were not helpful with examination of the association between thimerosal and vaccines. Each of the other four papers might help with a study of the schedule.

Fombonne et al. (2006) examined the prevalence of PDD in relation to two aspects of the immunization schedule in Canada: cumulative thimerosal dose and a change in the MMR schedule from one to two doses in birth cohorts from 1987 to 1998. Thimerosal was eliminated in 1996, and a second MMR (administered at age 18 months) was added to the schedule in 1996. Data on autism were from school records. Vaccine data were in part from a registry and in part from provider records. The dose of thimerosal was calculated from the recommended immunization schedule by year (not the dose received by individual children). A continuous increase in the incidence of PDD occurred over time, despite the elimination of thimerosal, and a decrease in MMR coverage was also detected. The increased rate of PDD was the same before and after the addition of a second required dose of MMR. The study was limited by reliance on administrative codes for the diagnosis of PDD. The study was also conducted in one school board (district), and some PDD cases may have moved into that board, which would have inflated the numbers. This was an ecological study, but the data were interpreted carefully and the differences in appropriate trends were noted.

Andrews et al. (2004) used the United Kingdom GPRD to evaluate the risk of a variety of neurodevelopmental disorders, including autism, tics, speech and language delay, attention deficit disorder, and other developmental delays, in association with the calculated cumulative exposure to thimerosal to up to 4 months of age in more than 100,000 children born between 1988 and 1997. The retrospective cohort study found no evidence for an increased risk of neurodevelopmental disorders, with the possible



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