MMR Vaccine and Autism: A new study in the British Medical Journal
Go right to Abstract
The February 17, 2001 issue of the British Medical Journal
contains another study that also fails to show a link between MMR vaccine and autism.
The article will be published in the print edition of an upcoming issue
(see the Abstract below).
The United Kingdom (U.K.) General Practice Research Database (UKGPRD) has complete
data on immunization for essentially the entire childhood population. Universal
MMR vaccination in the U.K. began in 1988. Between 1988 and 1993 vaccine coverage
was 97%. These authors did a time trend analysis of the database to discern a
possible link between MMR vaccine and autism. It was not possible to do a case-control
study since there were so few unvaccinated children.
The trend over time (1988-1999) in 305 children, aged 12 years or less, showed a
seven-fold increase in the incidence of autism (from 0.3 per 10,000 person-years
(1988 birth cohort) to 2.1 per 10,000 person-years (1999 birth cohort). Each
annual birth cohort, beginning with 1988, was analyzed for the first year of
recorded diagnosis of autism during a 4 year period between ages 2 and through
5 years. This is an estimate of the "four year cumulative incidence (risk)."
The peak ages of initial diagnosis were 3 and 4 years. The median age of
diagnosis was 4.6 years. The diagnosis of autism was submitted by the general
practitioner to the UKGPRD. It is not known if a specialist actually made a
diagnosis. Of course, the period of study also straddles the DSM-III-R and DSM-IV
The prevalence of MMR vaccine coverage was also calculated for each annual birth
cohort for children who had at least two years of recorded follow-up in the UKGPRD.
The possibility of a temporal association between MMR vaccination and
autism was studied in successive birth cohorts of 114 boys born between 1988
and 1993 in whom the diagnosis of autism was recorded during the four year risk
period (ages 2 through 5 years). The authors do not explain why further
analysis was restricted to boys. (Of course, there were more boys which may
have enhanced the statistical power of the analysis.) Vaccine status could be
assessed in 110 of the boys with autism, of whom 109 received MMR. The cumulative
four year risk of autism increased from 8 per 10,000 for boys born in 1988
to 29 per 10,000 for boys born in in 1993. This trend occurred during the period
beginning in 1988 when the prevalence of MMR vaccination in the general population
was essentially constant at about 97%. The median age of vaccination was
14 months, with 95% of children having received vaccine by 20 months of age.
The vaccine coverage in the group diagnosed with autism was 99%, slightly
higher than in the general population.
Since the incidence of autism continued to rise during the period when MMR
vaccine coverage was constant and nearly universal, these data fail to confirm
a link between the vaccine and autism. Since the level of risk, if MMR is
to be implicated, was the same for each of the birth cohort years, 1988-93,
the incidence of autism should have been flat, paralleling the flat line
(at 97%) of vaccine coverage. The fact that the trend was one of a progressive
increase supports other factors, such as "increased awareness of the
condition, changing diagnostic criteria, or environmental factors not
yet identified." The authors conclude that "these results provide
evidence against a causal relation between MMR vaccination and the risk
Full text of the article,
including a PDF version
Mumps, measles, and rubella vaccine and the incidence of autism recorded
by general practitioners: a time trend analysis
James A Kaye, Maria del Mar Melero-Montes, Hershel Jick
Boston Collaborative Drug Surveillance Program, Boston University School of
Medicine, 11 Muzzey Street, Lexington, MA 02421, USA
James A Kaye, epidemiologist
Maria del Mar Melero-Montes, epidemiologist
Hershel Jick, associate professor of medicine
Correspondence to: J A Kaye [email protected]
Objective: To estimate changes in the risk of autism and assess the relation
of autism to the mumps, measles, and rubella (MMR) vaccine.
Design: Time trend analysis of data from the UK general practice research database (GPRD).
Setting: General practices in the United Kingdom.
Subjects: Children aged 12 years or younger diagnosed with autism 1988-99,
with further analysis of boys age 2 to 5 years born 1988-93.
Main outcome measures: Annual and age specific incidence for first recorded
diagnoses of autism (that is, when autism was first recorded) in the children
aged 12 years or younger; annual, birth cohort specific risk of autism diagnosed
in the 2 to 5 year old boys; coverage (prevalence) of MMR vaccination in
the same birth cohorts.
Results: The incidence of newly diagnosed autism increased sevenfold, from
0.3 per 10 000 person years in 1988 to 2.1 per 10 000 person years in 1999.
The peak incidence was among 3 and 4 year olds, and 83% (254/305) of cases
were boys. In an annual birth cohort analysis of 114 boys born in 1988-93,
the risk of autism in 2 to 5 year old boys increased nearly fourfold over
time, 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. For the same annual
birth cohorts the prevalence of MMR vaccination was over 95%.
Conclusions: Because the incidence of autism among 2 to 5 year olds
increased markedly among boys born in each year separately from 1988 to
1993 while MMR vaccine coverage was over 95% for successive annual birth
cohorts, the data provide evidence that no correlation exists between the
prevalence of MMR vaccination and the rapid increase in the risk of autism
over time. The explanation for the marked increase in risk of the diagnosis
of autism in the past decade remains uncertain.
Abstract © 2001, British Medical Journal