http://content.nejm.org/cgi/content/abstract/347/19/1477?ijkey=p4J.EJxP2/wIk

A Population-Based Study of Measles, Mumps, and Rubella Vaccination and Autism
Kreesten Meldgaard Madsen, M.D., Anders Hviid, M.Sc., Mogens Vestergaard, M.D., Diana Schendel, Ph.D., Jan Wohlfahrt, M.Sc., Poul Thorsen, M.D., Jørn Olsen, M.D., and Mads Melbye, M.D.

ABSTRACT

Background It has been suggested that vaccination against measles, mumps, and rubella (MMR) is a cause of autism.

Methods We conducted a retrospective cohort study of all children born in Denmark from January 1991 through December 1998. The cohort was selected on the basis of data from the Danish Civil Registration System, which assigns a unique identification number to every live-born infant and new resident in Denmark. MMR-vaccination status was obtained from the Danish National Board of Health. Information on the children's autism status was obtained from the Danish Psychiatric Central Register, which contains information on all diagnoses received by patients in psychiatric hospitals and outpatient clinics in Denmark. We obtained information on potential confounders from the Danish Medical Birth Registry, the National Hospital Registry, and Statistics Denmark.

Results Of the 537,303 children in the cohort (representing 2,129,864 person-years), 440,655 (82.0 percent) had received the MMR vaccine. We identified 316 children with a diagnosis of autistic disorder and 422 with a diagnosis of other autistic-spectrum disorders. After adjustment for potential confounders, the relative risk of autistic disorder in the group of vaccinated children, as compared with the unvaccinated group, was 0.92 (95 percent confidence interval, 0.68 to 1.24), and the relative risk of another autistic-spectrum disorder was 0.83 (95 percent confidence interval, 0.65 to 1.07). There was no association between the age at the time of vaccination, the time since vaccination, or the date of vaccination and the development of autistic disorder.

Conclusions This study provides strong evidence against the hypothesis that MMR vaccination causes autism.
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BMJ 2002;325:1134 ( 16 November )

News

MMR vaccine is not linked with autism, says Danish study

Janice Hopkins Tanne, New York

A Danish study of more than half a million children showed no link between measles, mumps, and rubella (MMR) vaccination and autism.

In a commentary accompanying the study, which was published in the New England Journal of Medicine (2002;347:1477-82)[Abstract/Free Full Text], Dr Edward Campion, senior deputy editor, wrote, "This careful and convincing study shows that there is no association between autism and MMR vaccination."

Lead author Dr Kreesten Meldgaard Madsen, an epidemiologist and expert on infectious diseases at the Danish Epidemiology Science Centre in Aarhus, told the BMJ that the study showed that the risk of autism was similar in children who were vaccinated and children who were not.

The study reviewed records of 537303 children born in Denmark between January 1991 and December 1998, representing almost 100% of children born in that period. Of these children 440655 had been vaccinated. Records were retrieved from three sources: the unique identification number assigned to each child at birth; MMR vaccination data reported to the National Board of Health by general practitioners, who give all MMR vaccinations and are reimbursed for their reports; and diagnoses of autism recorded in the Danish Psychiatric Central Registry. Only specialists in child psychiatry diagnose autism and related conditions.

The study considered the children's sex, weight and gestational age at birth, and age at diagnosis of autism or of a related disorder; the socioeconomic status of the parents; and the mother's education.

The authors found that "There was no increase in the risk of autistic disorder or other autistic-spectrum disorders among vaccinated children as compared with unvaccinated children (adjusted relative risk of autistic disorder, 0.92; 95% confidence interval, 0.68 to 1.24; adjusted relative risk of other autistic-spectrum disorders, 0.83; 95% confidence interval, 0.65 to 1.07)."

In addition, the authors found no association between the development of autistic disorder and the age at vaccination, the interval since vaccination, or the calendar period at the time of vaccination.

Children were vaccinated at 15 to 17 months, and catch up vaccination was given to older children when the vaccine was introduced in 1987. Almost all children were vaccinated before the age of 3 years. The mean age at diagnosis for autism was 4 years, 3 months, and for autistic spectrum disorders 5 years, 3 months.

Although MMR vaccination was introduced in Denmark in 1987, the rise in autism began only in the mid-1990s. "If it [MMR vaccination] caused autism, we would see a greater risk [soon] after its introduction," Dr Madsen said, but the study did not show that. Autism is increasing, perhaps because of better diagnosis, but there is no link to MMR vaccination, he said.

The retrospective nature of the study may be its strength, Dr Madsen told the BMJ. Recall bias, such as when parents whose children are given a diagnosis of autism recall events that occurred around the time of the diagnosis, was absent. In this study, data on vaccination were recorded separately from data on diagnosis.

MMR vaccination protects children against disease, Dr Madsen said. "Measles kills one in 3000 children, even in developed countries. It causes encephalitis in one in 2000 and pneumonia in one in 20. People tend to forget."
 

ENGLISH COMMENT BY SIEM

Approximate reconstruction of the data for the study, assuming that all cohorts are the same size: 537,304 children divided into 8 cohorts

stora, 537 304 barn i studien, 8 årskullar.
 

This reconstruction illustrates how the oldest cohort born in 1991, contributes 67,163 person-years during each and every one of the 8 calendar years. The youngest cohort, born in 1998, only contributes 67,163 person-years during one single year, however. The reconstruction gives a total of 2.4 million person-years, compared with the 2.1 million person-years stated in the study. The difference can be explained by minor variations of little significance in the cohorts from year to year.

The underlined figures indicate when vaccination normally takes place as part of the vaccination programme. The figures in italics indicate the point in time when autism is usually diagnosed in that age group: i.e. the fifth year of life - 1996 for children born in 1991 etc. This point is only reached by the three oldest cohorts. Children born in 1994 and later did not reach the age when autism is usually diagnosed before the study was concluded.

SOURCE OF ERROR # 1: Children did not have time to become autistic as a result of MMR vaccination before being excluded from the study

537,303 children multiplied by 12 years equals a total of 6.5 million person-years for children born between 1991 and 1998. Only 2.1 person-years have been taken into account, however. Younger children were only studied from the time of birth until the study was concluded. As a result, the oldest children contribute considerably more person-years to the study than the youngest children.

The average age for the entire population studied is 2.1/6.5 * 12 = approximately 4 person-years. As a result, observation of the subjects was discontinued long before the age when autism is normally diagnosed (4.25 - 5.25 years according to the study itself). Moreover, a second MMR vaccination is normally given during the fourth year of life.

The youngest cohorts have only just managed to get the MMR vaccine before they are discarded from the study. As a result, they contribute to the numbers of vaccinated children, but have little or no chance of being diagnosed with autism as a result of the vaccines they were given.

Children diagnosed with autism before they were old enough to be given the MMR vaccine may then have been included in the study as "unvaccinated autistic children".

This is a systematic and uncontrolled source of error. As a result, the possible role of the MMR vaccine as a cause of autism is consistently underestimated.

SOURCE OF ERROR #2: Cases of congenital autism and cases of autism as a result of previous vaccinations withother vaccines also obscure the issue and reduce the effect of those few cases of autism caused by the MMR vaccine that are nonetheless detected.

Many experts on autism believe that some cases of autism are not caused by vaccination, but are congenital. These cases are usually diagnosed in the first year of life and often before the first MMR vaccine is administered. Moreover, the Danish study also seems to presume that only the MMR vaccine may cause autism, whereas numerous studies have shown that any vaccine is in fact capable of doing so. Books such as Dr Viera Scheibner's "Behavioural Problems in Childhood - The Link to Vaccination", Greg Wilson's "Vaccination and Behavioural Disorders - A Review of the Controversy", Harris Coulter's "Vaccination: Social Violence and Criminality, The Assault on the American Brain" and Karen Seroussi's "Unravelling the Mystery of Autism" examine the subject in great detail. The first two of these books alone cite over 500 relevant medical papers between them. However, it does not seem to have occurred to the authors of the Danish study that cases of autism caused by the MMR vaccine can hardly be diagnosed before the vaccine has been administered. Not only that: any cases of autism caused by the second MMR vaccine, which is normally administered in the fourth year of life, are unlikely to be detected by this study, since most of the older children are no longer included in the study by this time. Indeed, children in the later age cohorts no longer form part of the study before the effects of even the first MMR vaccine can be detected.

Most cases of congenital autism and many cases of autism caused by other vaccines will be detected by this study, but very few cases of autism caused by the MMR vaccine will show up. As a result, the significance of any such cases that are in fact found will be obscured by the cases of congenital autism and autism caused by other vaccines. The statistical effect of this is that groups that have received the MMR vaccine and those that have not will tend to exhibit a similar incidence of autism

This is a systematic source of error that makes it practically impossible to detect any cases of autism caused by the MMR vaccine

SOURCE. OF ERROR #3: Autistic children may have systematically been classified as unvaccinated.

According to the study, 18% of the children were unvaccinated, while 82% were vaccinated. Only by the age of three were children deemed, with certainty, to have been vaccinated. The average age when the MMR vaccine was given can be estimated as 1.5 years.

It is not clear how the study categorised children who were diagnosed with autism before the age of three, but who were given the MMR vaccine after they were diagnosed. Similarly, it is unclear how children who were given the MMR vaccine for the first time after the age of three were classified.

As for the reason why 18% of the children did not receive the MMR vaccine, this is neither studied nor commented upon. Contraindications to vaccination include poor health, lowered immunity, immunological processes, neurological diseases and neurological disturbances: in other words the very conditions indicative of the gastro-intestinal autism syndrome.

It is obvious that such cases must have existed. The fact that they are not commented upon can only indicate that the authors of the report have either not realised what the statistical effect would be or are deliberately seeking to conceal the effects of the MMR vaccine.

If doctors or parents have refrained from vaccinating for health reasons, whether real or suspected, these children will have been classified as "unvaccinated" and the conclusions of the report will be completely misleading.

SOURCE OF ERROR #4: The effect of relevant data has been diluted by irrelevant data.

If the intention is to compare the effects of vaccines on children, it is appropriate to compare vaccinated with unvaccinated children only AFTER vaccination. Mixing such data with data concerning children prior to vaccination only serves to obscure the issue and make any effects much harder to detect. At the same time the impression is given that the study is based on far more observations than is in fact the case.

Of the 2.1 million person-years studied, 537,303 * 1.5 = 0.8 million years represent unvaccinated children below 1.5 years of age (whether or not they were subsequently vaccinated). Of the remaining years (2.1 - 0.8 = 1.3 million person-years), 82%, or approximately 1.1 million person-years represent children older than 1.5 years who received the MMR vaccine. Only approximately 0.2 million person-years represent children over the age of 1.5 years who did not receive the MMR vaccine. Only in this group would it be possible to find a relevant control group to compare with those who did receive the MMR vaccine. It is this limited group that must form the basis for statistical evaluations of safety and level of incidence.

According to the study, 738 cases of autism were found that could be assigned to the population studied. All cases of autism diagnosed before the age at which the MMR vaccine was administered must naturally be discarded in order for any comparison to be meaningful. Generally speaking this would be 0.8/2.1 = 38% of the 738 cases reported (i.e. 280 cases). Of the remaining 458 cases, assuming the risk is the same for both vaccinated and unvaccinated children, 18% (82 cases) will be unvaccinated children older than 1.5 years. This represents 10 cases per year for the whole of Denmark.

SOURCE OF ERROR #5: The design of the study makes it extremely sensitive to any changes that take place over time.

It is well known that vaccines are not stable: both their quality and their contents are continually changing. An analysis of the studies conducted by Kayes and Taylor in England, for example, show that the introduction of the Urabe vaccine in 1992 was followed by a sudden and rapid increase in the incidence of autism. It is reasonable to assume that in Denmark as well there were changes in the characteristics of the vaccines used. Such changes are neither mentioned nor accounted for.

The design of the study means that the older cohorts (1992-1995) contribute far more person-years to the study. This means that just as in the English studies, any increase in the risk of autism over time is practically impossible to detect.

In addition, no information is given about how the unvaccinated group is distributed over the years 1991-1998. This in itself can seriously affect or distort the study.

TO SUM UP: The data presented in the study provides no basis whatsoever for the conclusions drawn by the authors.

The study tries to give the appearance of an exhaustive investigation of all children born in Denmark from 1991 to 1998. In reality only one third of the person-years attributable to these groups of children have been studied. Many of the person-years that have been studied are of no relevance whatsoever. Most of the person-years that would have provided the most valuable information have been excluded from the study, perhaps due to lack of time or other reasons. However, a more detailed examination of the oldest cohorts, which might have compensated for this shortcoming, has not been provided.

Important questions remain unanswered, such as whether children diagnosed with autism at an early age were classified as vaccinated or not, and whether or not the original decision to vaccinate or not vaccinate children is in itself a source of systematic error.

In the final analysis, the conclusions drawn by the authors of the study are based on a mere 10 cases per year. Given the numerous sources of error and the unclear definitions of the concepts used, this is totally inadequate.

All the sources of error identified in the study distort it in the same direction: obscuring the role of the MMR vaccine and exonerating it from any suspicion that it may cause autism. This strongly indicates deliberate fraud. The reason is not hard to guess. Most of the authors of the report are medical doctors and it is safe to assume that they are - or have been - ardent pro-vaccinators. By now they should be well aware of the many scientific studies of the injuries caused by vaccines. They will know that there is now an autism epidemic, that only the vaccinated are affected and that autism always occurs after vaccination and not before. In other words the authors of this report are people with blood on their hands, who fear the retribution of parents, whose children they have killed, mutilated and rendered autistic. People who are prepared to kill and injure helpless children for money will hardly hesitate to lie and cheat if it will keep them out of jail and enable them to avoid paying compensation to their victims. This report is a desperate and despicable attempt by child abusers to remove the noose that is tightening around their necks. Their report (and this one) belongs in the hands of the prosecutor.

Ulf Brånell

Alan Rees +46 40 163930 rees <rees@pp.sbbs.se>