Mumps, measles, and rubella vaccine and the incidence of autism recorded by general practitioners: a time trend analysis

British Medical Journal, Feb 24, 2001 by James A. Kaye, Maria del Mar Melero-Montes, Hershel Jick

Subsequent analyses were restricted to 114 boys born in 1988-93 who had a first recorded diagnosis of autism at age 2 to 5 years (24-71 months)--that is, during 1990-9. Annual birth cohorts were analysed separately. For each annual birth cohort, we estimated the four year cumulative incidence (risk) of diagnosed autism with the exponential formula: cumulative incidence = 1 - exp(- [Sigma][I.sub.k][Delta]t), where [I.sub.k] represents the estimated age specific annual incidences for the individual birth cohort and [Delta]t is one year. The prevalence of MMR vaccination among children registered in the general practice research database within 60 days of birth who had at least two years of recorded follow up was also calculated separately for each annual birth cohort. Statistical analyses were performed using STATA, version 7.0 (Stata Corporation, College Station, Texas).

Results

The estimated yearly incidence of diagnosed autism among children aged 12 years or younger (305 cases) increased sevenfold, from 0.3 per 10 000 person years in 1988 to 2.1 per 10 000 person years in 1999. The median age at first recorded diagnosis of autism was 4.6 years and did not vary substantially over time (table). The peak ages at first recorded diagnosis were 3 years and 4 years (fig 1). Two hundred and fifty four of the cases were male. About 81% (248/305) of the cases were referred to a specialist for evaluation of the diagnosis.

[Figure 1 ILLUSTRATION OMITTED]

Number of cases, person years at risk, and mean age of cases, according to year of diagnosis of autism in 305 children aged 12 years or younger.

                                      Estimated
                                    incidence per   Median age
Year of     No of   No of person    10 000 person    of cases
diagnosis   cases   years at risk       years        (years)

1988           7        255 771          0.3           6.0
1989           8        276 644          0.3           5.6
1990          16        295 901          0.5           5.0
1991          14        309 682          0.5           4.4
1992          20        316 457          0.6           4.0
1993          35        316 802          1.1           5.8
1994          29        318 305          0.9           4.6
1995          46        303 544          1.5           4.3
1996          36        260 644          1.4           4.7
1997          47        216 826          2.2           4.3
1998          34        161 664          2.1           5.4
1999          13         60 502          2.1           5.9
Total        305      3 092 742          1.0           4.6

To assess more precisely the possibility of a temporal association between MMR vaccination and the risk of autism, we analysed data for consecutive annual birth cohorts of boys born during 1988-93. For each annual birth cohort, we estimated the four year cumulative incidence (risk) of a first recorded diagnosis of autism at age 2-5 years. One hundred and fourteen boys were included in this analysis. The four year risk of diagnosed autism increased nearly fourfold, from 8 (95% confidence interval 4 to 14) per 10 000 for boys born in 1988 to 29 (20 to 43) per 10 000 for boys born in 1993 (P [is less than] 0.0001 by score test for trend in odds (fig 2)). In contrast, the prevalence of MMR vaccination among children registered in the general practice research database with at least two years of follow up was virtually constant (about 97%) for each successive annual birth cohort and was similar among males and females (data not shown).