Studies that Count, Studies that Don’t

[Guest guest]

Studies that Count, Studies that Don’t

F. Edward Yazbak, MD, FAAP

_http://www.vacinfo.org/studies.htm_ (http://www.vacinfo.org/studies.htm)

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.â€

 

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?â€

 

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 autismâ€. Interestingly, Kreesten

Meldgaard

Madsen, author of “A Population-Based Study of Measles, Mumps and Rubella

vaccination and Autismâ€, (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

designâ€

(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

persuasiveâ€. 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)

GRAHP HERE

 

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.â€) 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 HERE

 

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.

 

Conclusions

 

Autism has increased in Denmark after the introduction of the MMR vaccine as

evidenced by the fact that the rate ratio i.e. the incidence of autism after

vs. before MMR vaccination is 8.8 (95% C.I., 6.3 to 12.1) among 5 to 9 year

old Danish children.

 

The Madsen study did not reveal this statistically significant increase.

 

Dr. DeStefano and his colleagues at the CDC should research the causes of

Regressive Autism rather than defend a vaccine in trouble.

 

Parents are more likely to forgive errors than cover-ups.

 

References:

 

1. Yazbak FE. Autism in the United States: a Perspective. J Am Phys Surg

2003;

8:103-107

Available at _http://www.jpands.org/vol8no4/yazbak.pdf_

(http://www.jpands.org/vol8no4/yazbak.pdf) .

(accessed February 10, 2004)

2. Yazbak F E. Autism seems to be increasing worldwide, if not in London.

BMJ 2003;328:226227.

Available at _http://bmj.bmjjournals.com/cgi/content/full/328/7433/226-c _

(http://bmj.bmjjournals.com/cgi/content/full/328/7433/226-c%20(accessed)

_(accessed_

(http://bmj.bmjjournals.com/cgi/content/full/328/7433/226-c%20(accessed)

February 10, 2004)

3. Prevalence of Autism in Brick Township, New Jersey, 1998: Community

Report.

Available at _www.cdc.gov/ncbddd/pub/BrickReport.pdf_

(http://www.cdc.gov/ncbddd/pub/BrickReport.pdf) .

(accessed February 10, 2004)

 

4. Yeargin-Allsopp M, Rice C, Karapurkar T, Doernberg N, Boyle C, Murphy

C.

Prevalence of autism in a US metropolitan area. JAMA 2003;49-55.

 

5. Madsen MK, et. al. A population-based study of measles mumps rubella

vaccination and

autism. NEJM 2002;347:1478-1482

 

6. The Autism Epidemic is Real and Excessive Vaccinations Are the Cause

A Statement: Bernard Rimland, PH.D.July 14, 2003

Available at: _http://autismautoimmunityproject.org/Rimland.htm_

(http://autismautoimmunityproject.org/Rimland.htm)

(accessed February 10, 2004)

F. Edward Yazbak, MD, FAAP

TL Autism Research, Falmouth, Massachusetts

E-mail: _tlautstudy_ (tlautstudy)

February 25, 2004