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Epidemiology:
doi: 10.1097/01.ede.0000190553.72757.15
Letters: Letters to the Editor

Incidence of Autism Over Time

Jick, Hershel; Beach, Kathleen J.; Kaye, James A.

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Boston Collaborative Drug; Surveillance Program; Boston University School of Medicine; Lexington, Massachusetts; School of Public Health; University of Massachusetts; Amherst, Massachusetts

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To the Editor:

A dramatic rise of 4-fold or more in the incidence of “diagnosed” autism during the decade from the late 1980s to the late 1990s is well documented in Britain, parts of the United States, and Denmark. The evidence for this conclusion is reviewed in an article that also provides a credible explanation for this increase.1 Here, we extend the estimates of incidence of diagnosed autism based on the General Practice Research Database (GPRD) to include calendar years through 2004 to determine whether the incidence has continued to increase or has leveled off. Our data source was the UK population-based resource GPRD.2 GPRD computer-recorded diagnoses of autism have been shown to be valid in 80% or more of cases.3,4

Criteria for inclusion in this analysis were very similar to those used in our previous studies on incidence of autism.1 The base population consisted of males age 24 to 59 months who had been registered by a practice by 18 months of age. Cases of autism were required to have a first recorded diagnosis from 24 through 59 months (age 2–4 years).1 Person-time of follow-up for each child began accumulating at age 24 months and continued until the day before the child turned 60 months of age. We calculated annual autism incidence rates among children in this 3-year age range for each year from 1992 through 2004. Confidence intervals were calculated using modified Byar's formula.5 Trend analysis was conducted using Poisson regression model.

There were 308 incident cases of autism identified from 1992 to 2004 (440,332 person-years in the base population). We excluded 6 potential cases with evidence of severe organic brain disease before the diagnosis of autism. Before 1996 there was a steady increase in the annual incidence of autism of approximately 20% (incidence rate ratio = 1.17; 95% confidence interval = 1.06–1.30; Fig. 1). The incidence rate ratio estimates the annual relative increase in antism incidence using the first year of interest as the reference. After a peak incidence in 1999, the incidence rate remained stable from 2000 through 2004 (0.99; 0.88–1.10).

Figure 1
Figure 1
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Wakefield et al.6 in 1998 published a small series of case reports that suggested a causal connection between measles-mumps-rubella (MMR) vaccine and the risk of autism. This report was followed by Taylor et al.7 in 1999, who reported a progressive increase in the incidence of “diagnosed” autism as high as 33-fold in cohorts of children 0 to 5 years of age born in a region of England during the years 1979 through 1992. Taylor and colleagues concluded that exposure to MMR vaccine did not explain this dramatic rise.

A series of subsequent results based on the GPRD published in 20018 and 20031,9 documented that the apparent progressive increase in incidence of diagnosed autism in boys age 2–4 in the early 1990s continued until 1999.1,9 These articles also provided fully convincing evidence that neither MMR nor indeed any vaccines were responsible for the dramatic rise in diagnosed autism over the course of time.1,8 The results1 provided evidence that the rise in diagnosed autism was the result of a change in criteria for the diagnosis at the clinical level.

In the current study, we have extended our previous findings of an increasing cumulative risk of diagnosed autism of 20% per year in Britain in the 1990 birth cohort to the 1996 birth cohort9 and have found the increase in incidence has indeed leveled off in the years 2000 to 2004 (incidence rate ratio = 0.99). We also note that a major increase in the incidence of diagnosed autism occurred among 2- to 4-year-old boys, from approximately 5/10,000 person-years in 1998 to more than 10/10,000 person-years in 1999—1 year after the published article of Wakefield6 that received extremely heavy media attention. This finding provides further credence to the proposition that the diagnosis of autism is influenced by clinical perception and awareness of the symptoms, as well as by the public pressure that characterizes the tendency to make this diagnosis.

Hershel Jick

Kathleen J. Beach

James A. Kaye

Boston Collaborative Drug

Surveillance Program

Boston University School of Medicine

Lexington, Massachusetts

School of Public Health

University of Massachusetts

Amherst, Massachusetts

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REFERENCES

1. Jick H, Kaye JA. Epidemiology and possible causes of autism. Pharmacotherapy. 2003;23:1524–1530.

2. GRPD. Full Feature GPRD - The General Practice Research Database. Available at: www.GPRD.com/home. Accessed October 12, 2005.

3. Black C, Kaye JA, Jick H. The relation of childhood gastrointestinal disorders to autism: a nested case-control study using the UK General Practice Research Database. BMJ. 2002;325:419–421.

4. Smeeth L, Cook C, Frombonne E, et al. MMR vaccination and pervasive developmental disorders: a case-control study. Lancet. 2004;364:963–968.

5. Rothman KJ, Boice JD Jr. Epidemiologic Analysis With a Programmable Calculator (NIH Publication 79–1649). Washington DC: US Government Printing Office; 1979.

6. Wakefield AJ, Murch SH, Anthony A, et al. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorders in children. Lancet. 1998;351:637–641.

7. Taylor B, Miller E, Farrington CP, et al. Autism and measles, mumps, and rubella vaccine; no epidemiological evidence for a causal association. Lancet. 1999;353:2026–2029.

8. Kaye JA, Melero-Montes MM, Jick H. Mumps, measles, and rubella vaccine and the incidence of autism recorded by general practitioners: a time trend analysis. BMJ. 2001;322:460–463.

9. Jick H, Kaye JA, Black C. Changes in risk of autism in the U.K. for birth cohorts 1990–1998. Epidemiology. 2003;14:630–632.

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© 2006 Lippincott Williams & Wilkins, Inc.

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