Chapter 27

Autism spectrum disorder (ASD) is a behaviorally defined neurologically-based developmental disorder with an onset before 3 years of age. ASD encompasses three diagnoses: autism, Asperger disorder (AD), and pervasive developmental disorders not otherwise specified (PDD-NOS). Autism is defined by abnormal development and/or regression in social interaction and communication along with repetitive and stereotyped interests and behaviors.1 Although the DSM-IV-TR also lists disintegrative and Rett disorder as subtypes of ASD, the former is rarely diagnosed and the latter is recognized as a distinct neurodegenerative disorder. Diagnosis of autism is usually made around the age of 18 to 24 months, although, upon reflection, parents typically report concerns in the first year of life. This gap between parents' early concerns and the relatively late diagnosis, along with the importance of early intervention, highlights the necessity to find reliable tools for early diagnosis. Recent studies have suggested that symptoms of autism may be detectable as early as 14 months of age using standardized assessments.2 ASD associated with developmental regression accounts for approximately one-third of the cases and usually occurs between the first and second years of life. Late-onset developmental regression, particularly after 3 years of age, highly suggests an underlying neurological disorder.

The prognosis of ASD is variable. It has been estimated that 40% to 70% of children with ASD will manifest subnormal intellectual function with higher early levels of intellectual, adaptive, language, and social function predictive of later autism symptoms and acquisition of cognitive skills.3-5 Data collected through the Autism and Developmental Disabilities Monitoring Network from 14 surveillance areas in the United States suggest that the average prevalence of ASD as 6.6 per 1000 children (approximately 1:150), with this prevalence ranging from 3.3 to 10.6 per 1000 children.6 These data also suggested that the previously noted increase in the prevalence of ASD has recently stabilized and confirmed previous reports that ASD is more prevalent in males than females with a ratio ranging from 3.4:1 to 6.5:1.6

The etiology of ASD is unknown, but it is becoming clear that ASD probably results from a genetically vulnerable individual being exposed to an environmental agent or endogenous stressor during a critical period in development. This so-called triple hit hypothesis attempts to account for both the complex nature of this disorder and lack of simple associations found between ASD and genetic markers.7 Investigation of environmental pollutants has been facilitated by modern information technology. Studies have linked clinical databases coordinated by the Centers for Disease Control and Prevention with monitoring databases from the Environmental Protection Agency.8,9 Such studies have suggested that environmental toxins, particularly mercury, may be related to an increased risk of ASD.8-10 The role of immunizations containing thimerosal, a mercury-containing preservative, is still unclear. While recent large-scale studies have demonstrated little influence of thimerosal on neuropsychological outcomes in childhood,11 meta-analysis of epidemiologic studies and a comparison of outcomes of children receiving vaccines containing different amounts of ...

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