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Danish Autism Studies: Conflicted Data

 

F. Edward Yazbak MD

 

Several Danish autism studies were published over the last eleven years. Some examined the autism-vaccine angles and some were funded or otherwise supported by the Centers for Disease Control and Prevention (CDC).

At its February 9, 2004 meeting, the Immunization Safety Review Committee of the Institute of Medicine (IOM) reviewed the available evidence related to vaccinations and autism, including certain Danish studies conveniently published in 2002 and 2003. The Committee issued its report on May 14, 2004[i] and concluded that the “body of epidemiological evidence” favored rejection of a causal relationship between MMR vaccination and autism and between thimerosal-containing vaccines and autism.

The committee also recommended “that available funding for autism research be channeled to the most promising areas.” My protest 8 years ago to the President of the Institute of Medicine[ii] has yet to be answered.

In this review, I will simply try to compare the autism and ASD counts listed in 3 of the Danish vaccine-related studies that were published in 2002 – 2003 (and considered at the February 9, 2004 meeting discussed above) with reciprocal autism or ASD counts from two non-vaccine-related Danish studies published in 2004 and 2013.

All autism/ASD counts in Danish studies reportedly originate from the same source.

 

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The selected three vaccine–autism reports will be referred to as Madsen-2002, Hviid-2003 and Madsen-2003. The two non-vaccine-related reports will be referred to as Lauritsen-2004 and Grønborg 2013.

Author affiliation, funding /support, pediatric population examined and number of affected children were all obtained from the respective studies.

Madsen-2002 [MMR]

Madsen KM, Hviid A, Vestergaard M, Schendel D, Wohlfahrt J, Thorsen P, Olsen J, Melbye M. 

A population-based study of measles, mumps, and rubella vaccination and autism. N Engl J Med. 2002 Nov 7;347(19):1477-82.

Author Affiliation: From the Danish Epidemiology Science Center, Department of Epidemiology and Social Medicine, Århus, Denmark (K.M.M., M.V., P.T., J.O.); the Danish Epidemiology Science Center, Department of Epidemiology Research, Statens Serum Institute, Copenhagen, Denmark (A.H., J.W., M.M.); and the National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta (D.S.).

Funding / Support: “Supported by grants from the Danish National Research Foundation; the National Vaccine Program Office and National Immunization Program, Centers for Disease Control and Prevention; and the National Alliance for Autism Research.”

Pediatric population examined: “We conducted a retrospective cohort study of all children born in Denmark from January 1991 through December 1998.”

Affected children: 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.”

 

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Hviid-2003

Hviid A, Stellfeld M, Wohlfahrt J, Melbye M.

Association between thimerosal-containing vaccine and autism. JAMA. 2003 Oct 1;290(13):1763-6.

Author Affiliation: Danish Epidemiology Science Center, Department of Epidemiology Research

(A.H., J.W., M.M.) and Medical Department (M.S.), Statens Serum Institut, Copenhagen.

Funding / Support: “Study was supported by grant 11 from the Danish National Research Foundation and grant 22-02-0293 from the Danish Medical research Council.”

Pediatric population examined: “Population-based cohort study of all children born in Denmark from January 1, 1990 until December 32, 1996 (N=467450)…”

Affected children: “During 2986654 person-years we identified 440 autism cases and 787 cases of other autistic spectrum disorders. The risk of autism and other spectrum disorders did not differ significantly between children vaccinated with thimerosal-containing vaccines and children vaccinated with thimerosal-free vaccines…”

 

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Madsen-2003

Kreesten M. Madsen, MD*; Marlene B. Lauritsen, MD‡; Carsten B. Pedersen, Msc§; Poul Thorsen, MD, PhD*; Anne-Marie Plesner, MD, PhD¶; Peter H. Andersen, MD¶; and Preben B. Mortensen, MD, DMSc§

Thimerosal and the Occurrence of Autism: Negative Ecological Evidence From Danish Population-Based Data. Pediatrics 2003;112;604-606

Author Affiliation: From the *Danish Epidemiology Science Centre, Department of Epidemiology and Social Medicine, University of Aarhus, Denmark; ‡Institute for Basic Psychiatric Research, Department of Psychiatric Demography, Psychiatric Hospital in Aarhus, Risskov, Denmark; §National Centre for Register- Based Research, University of Aarhus, Aarhus, Denmark; and the ¶State Serum Institute, Department of Medicine, Copenhagen, Denmark.

Acknowledgements: “The activities of the Danish Epidemiology Science Centre and the National Centre for Register-Based Research are funded by a grant from the Danish National Research Foundation. This study was supported by the Stanley Medical Research Institute. No funding sources were involved in the study design.

We thank Coleen Boyle, Diana Schendel, and Jose F. Cordero for comments and advice during preparation of the manuscript.”

Pediatric population examined: “All children between 2 and 10 years old who were diagnosed with autism during the period from 1971–2000.”

Affected children: “A total of 956 children with a male-to-female ratio of 3.5:1 had been diagnosed with autism during the period from 1971–2000…”

 

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Lauritsen-2004

M B Lauritsen, C B Pedersen and P B Mortensen

The incidence and prevalence of pervasive developmental disorders: a Danish population-based study. Psychological Medicine, 2004, 34, 1–8. f 2004 Cambridge University Press DOI: 10.1017/S0033291704002387 Printed in the United Kingdom

Author Affiliation: Department of Psychiatric Demography, Psychiatric Hospital in Aarhus, Denmark; National Centre for Register-Based Research, University of Aarhus, Aarhus, Denmark

Acknowledgement: The National Centre for Register-Based Research is financially supported by the Danish National Research Foundation. The study was supported by the Stanley Medical Research Institute and grants from the Beatrice Surovell Haskell Fund for Child Mental Health Research of Copenhagen.

Pediatric population examined: “The annual and age-specific prevalence and incidence rates of childhood autism, atypical autism, Asperger’s disorder, and pervasive developmental disorder not otherwise specified (PDDNOS) in Denmark during the period 1971–2000 in children younger than 10 years were estimated using data from the Danish Psychiatric Central Register.”

Affected children: “2061 cases with the PDDs studied were identified.”

“A total of 2061 children younger than 10 years of age were identified as having childhood autism, atypical autism, Asperger’s disorder, or PDD-NOS. From 1971 to 2000, 759 children (78% males) were diagnosed with childhood autism, and 285 (73% males) were diagnosed with atypical autism… From 1994 to 2000, a total of 419 children (94% males) were diagnosed with Asperger’s disorder and 806 (82% males) with PDD-NOS. Among children with childhood autism, atypical autism, Asperger’s disorder and PDD-NOS a total of 135 (18%), 63 (22%), 60 (14%), and 153 (19%) respectively, were ever diagnosed with one of the other PDDs studied.”

 

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Grønborg-2013

Therese K. Grønborg, MSc; Diana E. Schendel, PhD; Erik T. Parner, MSc, PhD

Recurrence of Autism Spectrum Disorders in Full and Half-Siblings and Trends Over Time - A Population-Based Cohort Study.

JAMA Pediatr. 2013 Aug 19. doi: 10.1001/jamapediatrics.2013.2259.

Author Affiliation: Section of Biostatistics, Department of Public Health, Aarhus University, Aarhus, Denmark (Grønborg, Parner); Centers for Disease Control and Prevention, Atlanta, Georgia (Schendel)

Funding/Support: “This study is funded by Aarhus University.”

Affected Children: [Data extracted from Table 3 of the publication]

Birth Year

Autism

Cases

ASD

Cases

1980-1984

114

782

1985-1989

259

1765

1990-1991

213

1228

1992-1993

317

1515

1994-1995

436

1864

1996-1997

457

1681

1998-1999

525

1542

2000-2001

517

1386

2002-2004

656

1401

Overall

3494

13164

 

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Comparing Numbers

While autism and ASD figures in Madsen-2002, Hviid-2003 and Grønborg-2013 are related to birth year, figures in Madsen-2003 and Lauritsen-2004 are related to year of diagnosis.  

I was personally told in 2003 that in Denmark, most cases of autism and ASD were usually diagnosed between the ages of 4 and 5 years.

According to Madsen-2002, the first study reviewed here: “The mean age at diagnosis was four years and three months for autistic disorder and five years and three months for other autistic-spectrum disorders.”

In an attempt to appropriately compare the data from all 5 studies, the dates of autism diagnosis of the Grønborg-2013 study will be considered the birth years listed + 4 and the dates of ASD diagnosis will be listed as the birth years + 5. As an example, the 114 cases of autism that were born from 1980 to 1984 will be presumed to have been diagnosed from 1984 to 1988 and the 1,401 ASD cases born in 2002-2004 will be presumed to have actually been diagnosed in 2007-2009.

The autism and ASD data in the above Grønborg table will look as follows when listed relative to “Birth Year” and/or “Year of Diagnosis”:

Birth Year

Year of

Autism

Diagnosis

Autism

Cases

Year of

ASD

Diagnosis

ASD

Cases

1980-1984

1984-1988

114

1985-1989

782

1985-1989

1989-1993

259

1990-1994

1765

1990-1991

1994-1995

213

1995-1996

1228

1992-1993

1996-1997

317

1997-1998

1515

1994-1995

1998-1999

436

1999-2000

1864

1996-1997

2000-2001

457

2001-2002

1681

1998-1999

2002-2003

525

2003-2004

1542

2000-2001

2004-2005

517

2005-2006

1386

2002-2004

2006-2008

656

2007-2009

1401

Overall

 

3494

 

13164

Table I

 

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I have carefully recorded the information included in the following three comparative tables. To the best of my knowledge, such comparisons have never been previously published.   

 

Danish Autism-ASD cases

As reported in

Madsen-2002 (MMR) --- Hviid-2003 (Thimerosal)

& Grønborg-2013

Study

Birth Dates

Interval

 

Autism                    Cases

ASD Cases

Total Cases

Madsen-2002

1991-1999

8 yr.

316

422

738

Hviid-2003

1990 -1997

7 yr.

440

787

1227

Grønborg-2013

1992 -1999

7yr

1735 *

6602^

8337

Table II

 

* 317+436+457+525

^ 1515+1864+1681+1542

Comments:

  • Hviid, Wohlfahrt and Melbye collaborated in Madsen-2002 and Hviid-2003
  • Schendel (CDC) co-authored Madsen-2002 and Grønborg-2013
  • Madsen-2002 and Hviid-2003 were published 11 months apart yet Hviid reported more cases of autism and ASD in a 7 year-period than Madsen did in an 8-year period, a discrepancy that was apparently not noted by the IOM Immunization Safety Review Committee 
  • In Grønborg-2013, the authors reported more cases of autism and ASD than both Madsen in 2002 and Hviid in 2003 did in about the same period of time
  • If the Grønborg data are accurate, then members of the Immunization Safety Review Committee of the IOM may have based their conclusions on faulty statistics

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Danish Autism-ASD cases

As reported in

Madsen-2003 (Thimerosal),

Lauritsen-2004 & Grønborg-2013

Study

Diagnosis

Period

Autism

ASD

Total

Madsen-2003

1971-2000

29 yr.

956

 

 

Lauritsen-2004

1971-2000

29 yr.

759

285

1044

Grønborg-2013

1984 -2000

16 yr.

1339*

 

 

Grønborg-2013

1985-1999

14 yr.

 

5290^

 

                                                                     Table III

* 114+259+213+317+436

^ 782+1765+1228+1515

Comments

Lauritsen, Pedersen and Mortensen who were involved in both Madsen-2003 and Lauritsen-2004 studies reported different numbers of autism cases in the two publications during the same period of time

Grønborg reported more cases of autism in a 16 year-period than Madsen reported in 29 years in his 2003 Thimerosal-autism study.

The discrepancy between the average numbers of ASD cases/year reported in Grønborg-2013 and Lauritsen-2004 is also noted with concern.

Thorsen co-authored both Madsen-2002 and Madsen-2003. 

***

 

Danish ASD cases

As reported in

Lauritsen-2004 & Grønborg-2013

Study

Diagnosis

Interval

ASD Cases

Lauritsen 2004

1994-2000

6 yr.

1225

Grønborg 2013

1995-1999

4 yr.

2743*

Grønborg 2013

1995-1996

1 yr.

1228


Table IV

 

* 1228 + 1515

Comments:

Grønborg reported more diagnosed ASD cases in 1 yr than Lauritson reported during a 6-year period. She also reported twice as many diagnosed cases in 4 years than Lauritsen reported in 6.

Both studies were not related to vaccines

*****

Summary

If my calculations and interpretations are correct, then a comprehensive and unbiased review of all Danish Autism/ASD-related studies published since 2002, whether vaccine-related or not, is in order.    

Doing nothing would certainly be unacceptable.

 

F. Edward Yazbak MD, Falmouth, Massachusetts

10-1-13

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