Feature Article

Prevalence and Risk Factors for Autism Spectrum Disorder

by Dr. Angelina Duggan and Jordana Schmier

Background

Autism Spectrum Disorder (ASD) is a descriptive term for a complex array of neurological diseases that includes infantile autism as first identified by Kanner in 1943 (Kanner 1943), atypical autism, and Asperger’s Syndrome (Asperger 1944). Autism is currently considered incurable, but research into causes and possible cures is ongoing. The increased diagnosis of ASD (Jick and Kaye 2003) and the lack of definitive information about what causes ASD has become an emotional societal issue, especially for parents searching for answers as to why their children are autistic. Explanations about the increased incidence, prevalence, and risk factors (associations and causes) of ASD remain either doubtful, unproven hypotheses, contentious, or still under investigation. There is intense debate about whether the recent apparent increased prevalence of ASD is a true increase or whether there are sources of bias influencing the diagnosis or inconsistencies in the temporal methodology/data.

Factors Influencing Prevalence

ChildPrior to 1985, the prevalence of autism was reported to be 25 per 10,000 children (Fombonne 1999). The Centers for Disease Control and Prevention (CDC) currently estimates a wide range of ASD prevalence rates, between 2 and 6 per 1,000. On a yearly basis, 24,000 children may be diagnosed with ASD (CDC 2005) in the United States.

Although it has not been established unequivocally, some scientists believe that the recent reported rise in the incidence and prevalence of ASD does not reflect a true increase in autism or ASD (e.g., Croen et al. 2002; Croen and Grether 2003; Fombonne 2002; Wing and Potter 2002; Yeargin-Allsopp et al. 2003). The determination of whether autism and/or ASD rates are increasing may be complicated by several issues:

Methodological differences:
Study design differences complicate comparing rates from newer studies with older studies (Fombonne 2002).
Changes in diagnostic criteria:
Variable diagnostic criteria have added to the difficulty in comparing rates over time.
Reporting errors:
Prevalence rates for infantile autism and ASD, although very different, may be incorrectly combined or delineated, resulting in under- or overreporting that has also made it difficult to evaluate actual temporal increases (Kwok 2003).
Misclassification:
Early epidemiology studies may have misclassified autism as mental retardation; some forms of mental retardation may be misclassified and confused with more extreme ASD that may also involve retardation (Croen et al. 2002).
Misdiagnosis:
Similarity of symptoms of ASD to other pervasive developmental disorders or learning disabilities could result in misdiagnosis and over-reporting of ASD.
Reproductive risk factors:
Older maternal age and lower birth weight have been associated with ASD; national trends suggest these concerns are becoming more significant.
Socioeconomic factors:
Affluent school systems may have increased awareness of developmental disorders and may have more resources available to assist these children if they are diagnosed.

ASD and Environmental Exposures

ChildCertain environmental substances (e.g., pesticides, chemicals, vaccines) have been proposed to cause ASD, but cause and effect exposure relationships have not been established. The potential involvement of the MMR vaccine and thimerosal (ethylmercury vaccine preservative) is extremely controversial despite an expert National Academy of Sciences Institute of Medicine report and other expert medical opinions that state neither is associated with increased autism (NAS IOM 2004; Parker et al. 2004; Kwok 2003).

The identification of gestational and postnatal environmental exposure is still under intense investigation. Neural tube closure disturbance on days 20–24 of gestation has been hypothesized as causing autism. Retinoids, a family of chemicals that includes vitamin A and other drugs for skin disorders, and thalidomide may disrupt development neural tube closure. A study of children exposed to thalidomide found that almost 25% of those exposed in utero during a specific, short time period had developed autism (Rodier et al. 1997).

Treatment and Government Sponsored Research

ChildCurrently, there is no cure for autism. Some social aspects of the condition can be treated and improved through intense and early individual behavioral interventions (NIMH/NIH 2005). Various agents, including psychotropic and anti-convulsion/ seizure medications, are being tried, but no one medication has been found to be entirely effective (Hellings 2000). Chelation therapy is dangerous and not approved by the U.S. Food and Drug Administration to treat ASD.

In utero genetic screening coupled with the determination of environmental risk factors may ultimately provide the basis for successful pre- and postnatal ASD interventions.

  • U.S. federal and state government agencies are providing significant funding for CDC monitoring and National Institutes of Health (NIH) research to elucidate ASD environmental and genetic causes and risk factors.
  • A joint project between the U.S. Environmental Protection Agency (EPA) and the National Institute of Environmental Health Sciences (NIEHS) has established centers at the University of California at Davis and University of Medicine and Dentistry in New Jersey to focus on possible environmental aspects of autism and related disorders (NIMH/NIH 2005).
  • The National Institutes on Deafness and Other Communications Disorders and National Institute of Child Health and Human Development, under NIH auspices, are funding a network of 10 Collaborative Programs of Excellence in Autism to conduct research on possible genetic, immunologic, and environmental factors.
  • Initiated in 2005, the Childhood Autism Risks from Genetics and the Environment (CHARGE) study is a 5-year collaborative study between the MIND Institute at the University of California, Davis, and NIH, to evaluate chemical and genetic factors in persons diagnosed with autism. The study will also have the capability to access and compare data to client-specific information in the California Department of Developmental Services databases.

Conclusion

While some social aspects of ASD can be treated and improved through behavioral interventions, the condition is currently considered incurable. Several types of pharmacological agents have been tried, but none is entirely effective. Chelation therapy, while used for treatment of lead poisoning, has not been approved for treating ASD in the U.S. State governments, CDC, NIH, EPA, and NIEHS, as well as academic centers, are funding multiple research projects to evaluate the role and interplay of environmental exposures, genetics, and immunological deficits as ASD risk factors.

References

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CDC. Autism Information Center. CDC, DHHS, Washington, DC. 2005. Accessed January 2006. www.cdc.gov/ncbddd/autism.htm.

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Fombonne E. The epidemiology of autism: A review. Psychol Med 1999;29:769–786.

Fombonne E. Epidemiological trends in rates of autism. Mol Psych 2002;7:S4–S6.

Hellings, J.A. 2000. Treatment of comorbid disorders in autism: Which regimens are effective and for whom? Available at: www.medscape.com. Accessed January 2000. MedGenMed 2(1). Medscape from WebMD.

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NAS IOM. Immunization safety review: Vaccines and autism. National Academy of Sciences, Institute of Medicine. National Academies Press, Washington, DC; 2004.

NIMH/NIH. HHS Report to Congress on autism activities. NIMH and NIH, DHHS, Washington, DC. 2005. Accessed January 2006. www.nimh.nih.gov/healthinformation/ autismmenu.cfm

Parker K, et al. Thimerosal-containing vaccines and autistic spectrum disorder: A critical review of published original data. Pediatrics 2004; 114:793–804.

Rodier PM, et al. Linking etiologies in humans and animal models: Studies of autism. Reprod Toxicol 1997;11:417–422.

Wing L, Potter D. The epidemiology of autistic spectrum disorders: Is the prevalence rising? Ment Retard Develop Dis Res Rev 2002;8:151–161.

Yeargin-Allsopp M, et al. Prevalence of autism in a US metropolitan area. JAMA 2003;289:49–55.

FOR MORE INFORMATION CONTACT:

Dr. Angelina Duggan is a Managing Scientist in Exponent’s Health Sciences practice, with more than 25 years of pharmaceutical and agrochemical industry experience in global regulatory affairs, product development of chemicals, and genetically engineered agrochemicals. She can be reached at 212-895-8110, or aduggan@exponent.com.

Ms. Jordana Kate Schmier is a Managing Scientist in Exponent’s Health Sciences practice. She has substantial expertise in quality of life assessment and instrument validation, outcomes research, modeling, and health economics. She can be reached at 571-227-7241, or jschmier@exponent.com.