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Vaccinationer og autisme

Kreesten Meldgaard Madsen  


  Download file   (1128 KB) (The PhD dissertation is in Danish language)

Accepted by: Sundhedsvidenskabeligt Fakultet Aarhus Universitet
Defended on: May 19, 2004
Official opponents: Johan Giesecke, professor , Kåre Mølbak, overlæge , Bo Christensen, institutleder
Tutors: Jørn Olsen, professor , Mads Melbye, professor

Published in the PhD Database: May 18, 2004


English abstract
Vaccines and autism ¿ Kreesten Meldgaard Madsen
The PhD thesis examines two hypotheses. It has been suggested that different vaccines cause autism. The wide-scale use of childhood vaccines has been reported to coincide with an apparent increase in the incidence of autism.
The first hypothesis relates the measles-mumps-rubella (MMR) vaccination to the development of autism. The second hypothesis connects the use of thimerosal-containing vaccines to the development of neuro-developmental disorders such as autism, attention deficit/hyperactivity disorder, and speech or language delay.
The hypothesis that MMR vaccination causes autism was proposed by Wakefield and co-workers who reported on children with signs of both developmental regression and gastrointestinal symptoms shortly after MMR vaccination. We conducted a follow-up study including all children born in Denmark from January 1991 through December 1998 ¿ altogether 537,303 children - and them followed through 1999. We found no difference in the risk for autism in vaccinated and unvaccinated children, even when other factors were taken into account, such as age at vaccination. The risk was similar in vaccinated and unvaccinated children both with respect to the narrow definition of autistic disorder and other autistic-spectrum disorders. Finally, there was no clustering of autism diagnoses in the time after vaccination, by age of the child at vaccination, or by date of vaccination. When reviewing the literature no convincing scientific evidence exists to support a causal relationship between the MMR vaccine and the subsequent development of autism. The biological plausibility rests on tenuous grounds and there is a sound body of epidemiological evidence to refute the hypothesis.
Thimerosal has been used as an antimicrobial agent in vaccines since the 1930s. It is metabolized into organic mercury compounds, which are well established as nephro- and neurotoxicants. However, mercury poisoning and autism do not affect the same sites or cells of the brain. Furthermore, there is no evidence of harm caused by the level of exposure experienced by children following the routine vaccination schedules in the US or Europe. By now, thimerosal has been phased out in most countries. If thimerosal was a common cause of autism; we would expect a drop in the incidence of autism following cessation of use. This decline was not observed in Denmark where thimerosal has not been used since 1992. Whether a decline will take place in countries that phased thimerosal out at a later stage than Denmark, time will tell.
It is concluded that nothing in the existing mass of data supports the hypothesis that vaccination causes autism and at present there is little scientific support to revisit the hypothesis. It is time to direct resources into other areas of vaccine research.

Bedømmere: Johan Giesecke, Sverige, Kåre Mølbak, Danmark og Bo Christensen, Danmark
Vejledere: Jørn Olsen, Danmark og Mads Melbye, Danmark







Danish abstract
Læge Kreesten Meldgaard Madsen
Vaccinationer og autisme
Ph.d.-afhandling udgår fra Center for Epidemiologisk Grundforskning, Aarhus Universitet og Statens Serum Institut.
Grundlaget for projektet er to hypoteser, som de senere år har skabt bekymring for, at der skulle være en sammenhæng mellem brugen af forskellige typer vacciner og den stigende forekomst af autisme. Formålet med ph.d.-projektet var ved anvendelsen af forskellige danske registre at undersøge to specifikke hypoteser, som omhandler børnevacciner og senere udvikling af autisme:
For det første undersøgte, hvorvidt MFR-vaccination er associeret med udviklingen af autisme. Vi undersøgte hypotesen i et historisk followupstudie af alle børn født i Danmark fra 1991 til 1998. Der har været mistanke om, at MFR-vaccinen kunne føre til udvikling af autisme hos vaccinerede børn. Studiet inkluderede 537.303 børn, hvoraf 738 blev diagnosticeret med autisme eller gennemgribende udviklingsforstyrrelser i løbet af opfølgningsperioden. Vi fandt ingen sammenhæng mellem MFR-vaccination og udviklingen af autisme.
For det andet undersøgte vi i et registerbaseret økologisk design, hvorvidt udfasningen af thimerosal fra børnevaccinationsprogrammet førte til et fald i incidensen af autisme. Thimerosal er et kviksølvholdigt konserveringsmiddel, som anvendes i vacciner. Det har i de senere år været debatteret, hvorvidt thimerosalholdige vacciner er en risikofaktor for udviklingen af autisme. Vi fandt at udfasningen af thimerosalholdige vacciner i Danmark i 1992 blev efterfulgt af en stigning i incidensen af autisme.
Konklusionen er, at undersøgelserne ikke støtter hypoteserne om at MFR-vaccinen og de thimerosalholdige vacciner er kausalt forbundet med autisme.

E-mail: kmm@dadlnet.dk
Forsvaret finder sted den 19. maj 2004, kl. 1400, Det Samfundsmedicinske Auditorium, Bygning 262, Vennelyst Boulevard 6, Aarhus Universitet.
Bedømmere: Johan Giesecke, Sverige, Kåre Mølbak og Bo Christensen
Vejledere: Jørn Olsen og Mads Melbye