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Studies that Count, Studies that Don’t
F. Edward
Yazbak, MD, FAAP
Parents
in England have a big choice: They can believe Andrew Wakefield or they can
believe Tony Blair, Liam Donaldson and Richard Horton. They can trust Andy or
they can trust the experts from the Committee on Safety of Medicines and the
Joint Committee on Vaccination and Immunization,
several of whom have ties with the drug company that distributes the MMR
in England.
We in the United States also have a
choice between on one side, clinical research, with real children and on the
other, one more epidemiological study by the CDC.
The following quotes from presentations on February 9, 2004 to the Vaccine
Safety Committee of the Institute of Medicine deserve attention:
“In light of encephalopathy, presenting in children as autistic regression
closely following MMR vaccination … The findings confirm a highly significant
statistical association between the presence of MV RNA in CSF and autistic
regression following MMR vaccination.” Jeff Bradstreet MD, Director,
International Child Development Resource Center, Melbourne, Florida.
“The current genetic research estimates that no more than 10% of all autistic
cases are genetic in origin. Simply put, the remainder 90% of autistic cases is
sporadic with a non-genetic etiology. I tend to think that the sporadic form is
by and large an “acquired” subset involving autoimmunity. This subset is likely
triggered by a virus, possibly measles virus or MMR vaccine...
Based upon our experimental
research, it is plausible to postulate that an atypical measles infection that
does not produce a typical measles rash but manifests neurological symptoms
might be etiologically linked to autoimmunity in autism. The source of measles
virus could potentially be MMR vaccine or a mutant measles strain, but more
research is necessary to establish either of these two possibilities…Fundamentally,
I tend to think that autistic children have a problem of their immune system,
which is the “faulty immune regulation.” Hence they have abnormal immune
reactions to measles virus and/or MMR vaccine” Vijendra K. Singh, Ph.D.,
Research Associate Professor of Neuroimmunology, Utah State University, an
international expert in the autoimmune causes of autism:
US Representative Dave Weldon, a physician, commenting on the on-going
clinical research said: “Mind you, half of Dr. Wakefield’s theory has
been proven correct and accepted in the medical community. Hundreds of children
with regressive autism and GI dysfunction have been scoped and clinicians are
seeing the inflammatory bowel disease he first described. The NIH is finally
funding an attempt to repeat Dr. O’Leary’s findings of measles RNA in
Wakefield’s biopsy specimens, though I am disappointed it has taken this long..A
clinician in New York was poised to repeat Wakefield’s work two years ago, but
he ultimately was refused by his IRB and then subsequently had his clinical
privileges withdrawn.”
Instead of telling parents why they are suddenly losing their children, the CDC
just published another long, pedantic and rather useless MMR “damage-control”
epidemiological study: Age at First Measles-Mumps-Rubella Vaccination in
Children with Autism and School-Matched Control Subjects: A Population-Based
Study in Metropolitan Atlanta by Dr. Frank DeStefano and others [Pediatrics
Vol. 113 No. 2 February 2004, 259-266].
The authors did not discuss the causes of the present epidemic now affecting the
United States (1) and the world (2), but simply stated that the MMR was unlikely
to be the cause of regressive autism because children diagnosed with autistic
disorders in Atlanta, Georgia received their first MMR vaccine at about the same
age as unaffected children.
The CDC had previously published two local epidemiological studies, in which
serious increases in autism were documented (3, 4). It also funded a third study
in Denmark (5) that, though much publicized, was flawed and irrelevant to the
situation in the United States. That study also seemed to have been primarily
intended to exonerate the MMR vaccine and it will be discussed in some detail
later.
The CDC has never proposed, designed, funded or carried out a single clinical
study on autism.
The only credible way to prove that the MMR vaccination does or does not
precipitate autistic symptoms in children, who are genetically predisposed and
have been previously exposed to Thimerosal-containing vaccines, is to compare
affected children who have received the MMR vaccine with children who have not.
This is obviously practically impossible because most children in Atlanta have
received the MMR vaccine. The theoretical question is therefore: “How many
children in Atlanta would have developed autism if they had not received the MMR
vaccine_”
A relatively easy study would be to compare the age of onset of autistic
symptoms in children vaccinated at 15 months and those vaccinated at 30 months
in Atlanta.
I believe, from my own research, that such a study will show that:
1. Autistic behavior follows MMR
vaccination and
2. That fewer cases and less
severe manifestations are noticed among the cohort vaccinated at 30 months,
since vaccination at a younger age appears most damaging.
Another easy study would be to compare Measles, MMR and Myelin Basic
Protein antibody titers of children who developed autism shortly after MMR
vaccination in Atlanta to an equal sample of normal children similarly
vaccinated.
Dr. DeStefano states [under conclusions, page 259] “Similar
proportions of case and control children were vaccinated by the recommended age
or shortly after (ie, before 18 months) and before the age by which
atypical development is usually recognized in children with autism (i.e. 24
months).” The CDC, certain pediatricians and the MMR lobby have
consistently argued that autism is not due to the triple vaccine because
autistic symptoms are “usually first noted” around the time the MMR is
administered and that therefore the relationship between the two events is
casual and not causal; in other words just a coincidence. Historically, this is
not so.
Kanner’s autism was known as Infantile Autism because affected children
exhibited symptoms in early infancy. The more recent form of the disease,
Regressive Autism, occurs at a older age with symptoms usually starting at
18 to 24 months or later: A child,
most often a boy who is developmentally, socially and verbally on par for his
age, suddenly stops acquiring new words and skills in the second year of life
and then actually regresses, losing speech, cognitive abilities and social
dexterity. Many parents have reported and documented such regression in their
children after MMR vaccination.
Bernard Rimland, Ph.D., Founder and President of the Autism Research Institute
(ARI), a full-time professional research scientist in the field of autism
for 45 years, stated after a thorough analysis of the extensive ARI database:
“Late onset autism, (starting in the 2nd year), was almost unheard of
in the ‘50s, ‘60s, and ‘70s; today such cases outnumber early onset cases 5 to
1, the increase paralleling the increase in required vaccines.” (6)
The study by DeStefano, though dazzling with figures and tables proves little,
just like the epidemiological studies by Taylor, Kaye and Dales that were
supposed to have previously “convincingly proven that there is no
relationship between MMR vaccination and autism”. Interestingly, Kreesten
Meldgaard Madsen, author of “A Population-Based Study of Measles, Mumps and
Rubella vaccination and Autism”, (5) the study funded by the CDC stated
“Studies designed to evaluate the suggested link between MMR vaccination and
autism do not support an association, but the evidence is weak and based on
case-series, cross-sectional, and ecologic studies; No studies have had
sufficient statistical power to detect an association, and none has a
population-based cohort design” (References 10-16).” In the Madsen
bibliography, reference 10 is the first Taylor study (The Lancet); reference 11
is the one by Kaye (BMJ) and reference 12 is the study by Dales (JAMA). For
reasons known only to him, Dr. DeStefano still mentioned the Taylor, Kaye and
Dales studies as reliable and listed them as references 23, 22 and 19
respectively.
Dr. DeStefano and Associates describe the Madsen MMR study as “particularly
persuasive”. In fact, that study, because of an integral flaw in its
design, could not have shown, that indeed there had been an increase in autism
after routine MMR vaccination was initiated in Denmark.
The following is part of the analysis by Dr. Gary Goldman and myself of data
from the Danish Psychiatric Central Register, the same data that Madsen used.
It clearly shows that there has been a serious increase in autism in
children under 14 in Denmark in the last few years. (Graph I)
Graph I Incidence of
Autism in Denmark by Age Group
Source: The Danish Psychiatric Central Register
The MMR vaccine was introduced in Denmark in 1987. It
has been estimated that only 70% of the 15-month old children received the
triple vaccine in 1987-1988. The percentage of vaccinated toddlers then reached
and remained at 80 to 88% for several years. It is estimated that in the last
three years about 95% of the 15-month old children in Denmark received the MMR
vaccine.
The present rise in autism in Denmark has clearly started 4 to 5
years after the introduction of the MMR vaccine and it appears to correspond
with the percentage of children who received the MMR.
The mean age at the time of diagnosis in Denmark is probably around 4.7 years
(“The mean age at diagnosis for
autism was 4 years, 3 months, and for autistic spectrum disorders 5 years, 3
months.”) Approximately 25% of autism
cases in Denmark are reported in children under the age of 5 with the remainder
75% of affected children being reported when they are 5 to 19 years old.
Given these percentages, any inferences
about disease in the under-5 group, in which the disease has not yet become
manifest, are potentially flawed.
The 2,129,864 person-years reported in the
Madsen study divided by the number of children 537,303 indicates that the
average age of the children in the study is less than 4 years (range 1 to
7 years). Those children would be 5 to 12 years old in 2003. Because the mean
age at diagnosis is 4.7 years in Denmark, the Madsen study could NOT have
detected many of the cases of autism that were subsequently diagnosed when
these children were older, thereby missing the temporal connection
between MMR vaccination and autism.
The 0-4 year old group of children (Graph I, black) remains the lowest from 1980
to 1991, because autism was/is rarely diagnosed under the age of 4 in Denmark.
The prevalence of autism in that age group starts climbing after 1991, 4
years after the introduction of the MMR vaccine, to become the second highest by
1993.
The 5 – 9 age group is the earliest cohort that received the MMR vaccine after
coverage has improved and is also old enough to be diagnosed. There are
consistently more and more affected children in this age grouping.
The 10 –14 age group (dark green) represents
the earlier cohort that first received the MMR vaccine,
but at
lower
coverage rates. Those affected children
aged 10 to 14 in 2003 were aged 1 to 5 in 1994. They reflect the startup of
the autism increase associated with the startup and progression of the MMR
vaccination program.
The 15 –19 age group (light green) were aged 1 to 5 in 1989; their number
increases but at a much slower rate than in the younger age groups.
Lastly, the 20 – 24 age group (brown) shows only a slight increase
starting in 1994 possibly because few if any of this cohort, received the MMR
vaccine at a vulnerable age.
Even when one takes into account the classification change that took place in
1993/1994 and the addition of outpatients to the database in 1995, it is evident,
when five additional years are considered, that the conclusions of the Madsen
group are invalidated and that the data appears to support the hypothesis
that increases in autism in Denmark, may be correlated with increases in
percentage coverage and number of children receiving MMR vaccination.
It is likely that in Graph I, the 0 – 4 year group of affected children
represents those who were not generally diagnosed earlier, that the 5 – 9 age
group represents the highest increase that occurred after wide-spread coverage
of the MMR vaccine and that the 10 – 14 age group represents the earlier cohort
that first received the MMR vaccine, but at a low coverage rate.
It is possible that the rate of autism will now level off at the higher rate
since children receiving MMR immunization have now saturated the age groups and
replaced individuals in the age groups that were previously unvaccinated.
Approximately 65,000 babies are born every year in Denmark. Graph I shows the
early slow ramp-up period due to low vaccination rates. When MMR vaccination
coverage improved beyond a certain level, from 1993 to 2001, there was a steady
and increasing trend in autism every year. That gradual rise leveled out after
the entire cohort aged <10 was almost “completely” vaccinated (vaccine coverage
at >95%). It is entirely possible that many of the children of the most affected
5 to 9 group, could have started with symptoms as early as the second year of
life.
The prevalence rate of autism in Danish children under the age of 14 has
increased by 729% from 17.67 per 100,000 Population in 1980 to 146.42 in
2002. (Graph II)
Graph II Children with Autism under Age 14 In Denmark per 100,000
Population.
Source:
The Danish Psychiatric Central Register.
The prevalence of autism in children and teens under the age of 14 in Denmark,
which was 131.42/100000 in the 7 years before the MMR vaccine, increased by
542% to 843.73/100000 in the last 7 years. Indeed, the prevalence of autism
in that group was 11% higher (146.42/131.42) in 2002 alone than in the combined
7 years before the introduction of the MMR vaccine.
Two doses of MMR are administered
in Denmark, one at age 15 months, and one at age 12 years. The data suggest that
the main concern is the vaccination given at age 15 months.
The prevalence of autism in Denmark in the 0 to 14 year-olds leveled off in the
last 3 years, when toddler MMR coverage reached the 95 – 98% level. The reason
why this did not take place in the United States in the 90’s was probably
because pediatric vaccines in the US contained Thimerosal, further supporting
the argument that the study was flawed in principle because countries with
strikingly different vaccination practices cannot and must not be compared.
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