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Circumcision and Autism: A Recent Danish Study

F. Edward Yazbak M.D.

 

For a period of time, the Centers for Disease Control and Prevention (CDC) had a love-fest with Danish Researchers who agreed to produce needed evidence that in spite of parental reports, MMR vaccination and Thimerosal containing vaccines played no role whatsoever in the increased prevalence in autism and autistic spectral disorders (ASD).

In 2005, I published “The CDC finances, writes and helps publish Danish research”, a discussion of five Danish studies. http://www.vaccinationnews.org/sites/default/files/DanishStudy2005.pdf

Those five Danish studies (DS) were:

DS 1: 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 PMID: 12421889

DS 2: Madsen KM, Lauritsen MB, Pedersen CB, Thorsen P, Plesner AM, Andersen PH, Mortensen PB. Thimerosal and the occurrence of autism: negative ecological evidence from Danish population-based data. Pediatrics. 2003 Sep;112(3 Pt 1):604-6. PMID: 12949291

DS 3: Hviid A, Stellfeld M, Wohlfahrt J, Melbye M. Association between thimerosal-containing vaccine and autism. JAMA. 2003 Oct 1;290(13):1763-6. PMID: 14519711

DS 4: Lauritsen MB, Pedersen CB, Mortensen PB. The incidence and prevalence of pervasive developmental disorders: a Danish population-based study. Psychol Med. 2004 Oct;34(7):1339-46.PMID 15697060

DS5: Larsson HJ, Eaton WW, Madsen KM, Vestergaard M, Olesen AV, Agerbo E, Schendel D, Thorsen P, Mortensen PB. Risk factors for autism: perinatal factors, parental psychiatric history, and socioeconomic status. Am J Epidemiol. 2005 May 15;161(10):916-25; discussion 926-8. PMID:15870155

Studies 1 and 5 were funded by the CDC and co-authored by Diana Schendel PhD, at the time a CDC (NCBDDD) epidemiologist.

Poul Thorsen MD, PhD co-authored DS1, DS2 and DS5.

Thorsen did very well for himself as a CDC Principal Investigator and Liaison between the United States and Denmark in autism-related matters for years. He served on the Faculties of two US universities and incredibly, even on the DSM-V Committee.

Dr. Thorsen’s most notable achievement was the embezzlement of a couple of million dollars from the research funds he had access to. His multiple Federal indictments and the fact that he was featured for a long while on the Most Wanted Fugitives List of the Office of the Inspector General, HHS did not seem to affect his serene post-CDC life or his continued employment in Denmark.

At the hospital where he is presently employed, Dr. Thorsen has resumed his research activities and his regular publications thanks to continued and generous funding from the CDC and the National Institutes of Health.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4575046/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3619127/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3215787/

The fact that Dr. Thorsen is supposedly “awaiting extradition to the United States” has not prevented him from enjoying his new beach house. In fact, had he been able to ship his Harley over, his “new life” would have truly been fantastisk.

To the relief of many, a pervasive feeling that Dr. Thorsen will never be returning to the US, seems to have descended over the greater Atlanta region.

The amazing “ThorsenSaga” has even just been reported in exquisite detail in “MASTER MANIPULATOR. The Explosive True Story of Fraud, Embezzlement And Government Betrayal at the CDC” By James Ottar Grundvig [Skyhorse Publishing Inc].

A movie cannot possibly be too far in the future!

Had Philip Seymour Hoffman been alive, he could have been the perfect Thorsen. 

***

The Statens Serum Institut

Statens Serum Institut (SSI) is an institute under the (Danish) Ministry of Health whose purpose is to prevent and control infectious diseases, congenital disorders and biological threats.

SSI’s tasks include:

  • Surveillance and research of congenital disorders
  • Advanced detection and control of infectious diseases and biological threats.
  • Providing Reference Laboratory Services for infectious, autoimmune, congenital and genetic disorders.
  • Ensuring the uninterrupted supply of vaccines, other biological products and diagnostic services through production and procurement.
  • Preparedness against any form of biological terrorism.
  • Research and Development in the Institute’s areas of activity at an international level.

Indeed, the Institute also strives to be a highly regarded and recognized national and international research, production and service enterprise. http://www.ssi.dk/english/service/aboutssi.aspx

Several authors who contributed to the above-listed vaccine-autism studies were employed at SSI.

***

For reasons I have not been able to ascertain, there seems to have been some cooling in relations between the CDC and Denmark including its Statens Serum Institut.

The hierarchy at the National Center for Birth Defects and Developmental Disabilities (NCBDDD) seems satisfied to state that:

A: It has been proved that neither MMR vaccination nor the Thimerosal in other pediatric vaccines had anything whatsoever to do with any of the autistic spectrum disorders. 

B: No one yet knows what causes autism.

From time to time, minor laboratory findings have been exploited to suggest that the autism epidemic may have been due to some genetic etiology. The only reliable fact is that to date, we have spent millions and millions of dollars on genetic research and there is little evidence that as a Nation, we got our money’s worth.

Heading the National Institute of Mental Health (NIMH) and ultimately responsible for Autism Research from 2002 to November 2015 was Director Thomas R. Insel MD, a psychiatrist and a former Psychiatry Professor at Emory University. As they were being reported, Dr. Insell usually described and explained every newly proposed autism–related genetic theory and or discovery.

On September 16, 2013, Dr. Insell published “In Vitro Veritas” where he intimated that some solid and believable genetic discovery had been found in the laboratory.http://www.nimh.nih.gov/about/director/2013/in-vitro-veritas.shtml

The Director’s post started “Over the past 6 months we have turned a corner in our studies of the genetic basis of schizophrenia and autism. For years the field of psychiatric genetics has struggled: family and twin studies demonstrated that these disorders were heritable, but findings from small studies reporting specific risk genes could not be replicated. With larger samples and better tools, we have gone from famine to feast, with almost too many genetic findings to follow up. A new report has just described 13 new genetic findings associated with schizophrenia, resulting in over 100 common variants now identified as risk factors.” [End of quote]

I commented on Dr. Insell’s claims by publishing a month later: “An Autism-Gene in a Dish v In Vivo Veritas’.

http://www.vaccinationnews.org/2013-10-15-Autism-Gene-in-a-Dish-v-In-Vivo-Veritas-YazbakFE

Apparently, the magic genetic “feast” that Dr. Insell celebrated seemed to have turned back into famine, quietly.

***           

The folks at NCBDDD and CDC, possibly distracted by echoes from a whistle blower, completely missed a very important All-Danish autism study that was published in July 2015 and that, for a welcome change, had cost us nothing. Like in previous Danish autism-related reports, this most recent investigation examined a “National Cohort” for several years. For the purpose of a perspective, the population of Denmark was 5,690,750 in 2015 and the population of Maryland during the 2010 census was 5,773,552.

I must confess that in spite of several hours spent daily reading anything related to autism and associated issues, I also missed this most recent Danish study when it was published.

“Ritual circumcision and risk of autism spectrum disorder in 0- to 9-year-old boys: national cohort study in Denmark” by Morten Frisch and Jacob Simonsen was published in the prestigious Journal of the Royal Society of Medicine. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4530408/

Professor Morten Frisch, MD, PhD, DSc is a Consultant and Senior Investigator, Statens Serum Institut and Adjunct Professor of Sexual Health Epidemiology at Aalborg University. Professor Frisch published several studies. In 2013, he was the lead author of  Marriage, cohabitation and mortality in Denmark: national cohort study of 6.5 million persons followed for up to three decades (1982-2011)”. (Int J Epidemiol 2013; 42:559-578). In 2014, Professor Frisch was the lead author of “Same-sex marriage, autoimmune thyroid gland dysfunction and other autoimmune diseases in Denmark 1989-2008”  [Eur J Epidemiol 2014:29:63-71]

Co-Author Jacob Simonsen is a statistician, Department of Epidemiology Research, Division of National Health Surveillance and Research at the Statens Serum Institute. Mr. Simonsen was the lead author of Socioeconomic risk factors for bacterial gastrointestinal infections.”(Epidemiology 2008;19:282-290). He also co-authored several other studies.

***

I would like to state very clearly that I have the greatest respect for all religions and traditions mentioned in this report. To my knowledge, this may be the first time that circumcision and autism are discussed together in a US publication.

A Pub-Med search of “Circumcision” and “Autism” on May 2, 2016 revealed the presence of seven (7) publications. The presently discussed article is listed as #4.

Listed as #2 is 'Circumcision pain' unlikely to cause autism by Morris BJ, Wiswell TE.

https://www.ncbi.nlm.nih.gov/pubmed/26268916

Listed as #1 (most recent) is Circumcision-autism link needs thorough evaluation: Response to Morris and Wiswell. Frisch M, Simonsen J.

https://www.ncbi.nlm.nih.gov/pubmed/26268917

***

In their July 2015 publication, Frisch and Simonsen stated that:

  • Their Study was a Danish National Register-based “Cohort Study” of 342,877 boys born between 1994 and 2003 and followed from birth to age 9 years between calendar years 1994 - 2013.
  •  “Information about cohort members’ ritual circumcisions, confounders and ASD outcomes, as well as two supplementary outcomes, hyperkinetic disorder and asthma, was obtained from national registers. Hazard ratios (HRs) with 95% confidence intervals (CIs) associated with foreskin status were obtained using Cox proportional hazards regression analyses.”

*****

Reporting that the hazard ratios (HRs) with 95% confidence intervals (CIs) associated with foreskin status were obtained using Cox proportional hazards regression analyses, the authors list their results as follows:

“With a total of 4986 ASD cases, our study showed that regardless of cultural background circumcised boys were more likely than intact boys to develop ASD before age 10 years (HR = 1.46; 95% CI: 1.11–1.93). Risk was particularly high for infantile autism before age five years (HR = 2.06; 95% CI: 1.36–3.13). Circumcised boys in non-Muslim families were also more likely to develop hyperkinetic disorder (HR = 1.81; 95% CI: 1.11–2.96). Associations with asthma were consistently inconspicuous (HR = 0.96; 95% CI: 0.84–1.10).” (End of quote)

 The authors concluded in part:

“We confirmed our hypothesis that boys who undergo ritual circumcision may run a greater risk of developing ASD. This finding and the unexpected observation of an increased risk of hyperactivity disorder among circumcised boys in non-Muslim families, need attention, particularly because data limitations most likely rendered our HR estimates conservative. Considering the widespread practice of non-therapeutic circumcision in infancy and childhood around the world, confirmatory studies should be given priority.”

Important Note: Readers should read the complete publication to evaluate for themselves the careful research the authors undertook.

I will only list a few statements by the authors between quotation marks. Any comment I make will be clearly marked as such.

“Among children operated for a variety of conditions, Levy noted a strong association between the age at operation and the frequency and severity of emotional sequelae. Psychological problems were encountered in 42% of children aged <3 years at the time of operation, as compared with 10% among older children.1

http://archpedi.jamanetwork.com/article.aspx?articleid=1180027 (1945)

“Until recently, it was believed that newborns are incapable of interpreting noxious stimuli in a manner comparable to that of older children and adults. This idea has now been abandoned with almost universal consensus that newborns and infants perceive pain and stress very much like older children and adults.2  “

http://www.ncbi.nlm.nih.gov/pubmed/3317037  (1987)

“Regardless of surgical method, circumcision causes some level of pain and discomfort at the operation table and for several days after until wound healing has completed.10 “

http://www.ncbi.nlm.nih.gov/pubmed/22577918 (2012)

“The procedural pain associated with neonatal circumcision is plausibly more severe and the postoperative pain of longer duration than in older children and adults, because the foreskin of most neonates must be forcefully separated from the glans to which it is fused before it can be cut off.16  http://www.ncbi.nlm.nih.gov/pubmed/15408299  (1949) 

 “Neonatally circumcised boys in Canada exhibited significantly more signs of discomfort during routine vaccinations 4–6 months later than boys who were left intact, showing that early life trauma may alter a child’s future handling of pain.4 “  http://www.ncbi.nlm.nih.gov/pubmed/9057731  (1997)

“To our knowledge, no study has examined the possible association of circumcision-related pain and stress with boys’ subsequent risk of developing autism spectrum disorder (ASD).”

Comment: This is probably correct. After a thorough search, I could only find two statements that may have intimated some connection: 

In a study published in 2013 and devoted to the use of Tylenol and associated autism, the authors stated: “For studies including boys born after 1995, there was a strong correlation between country-level (n = 9) autism/ASD prevalence in males and a country's  circumcision rate (r = 0.98). A very similar pattern was seen among U.S. states and when comparing the 3 main racial/ethnic groups in the U.S. The country-level correlation between autism/ASD prevalence in males and paracetamol was considerably weaker before 1995 when the drug became widely used during   circumcision.” http://www.ncbi.nlm.nih.gov/pubmed/23656698

“The present investigation was prompted by the combination of recent animal findings linking a single painful injury to lifelong deficits in stress response25  http://www.ncbi.nlm.nih.gov/pubmed/23838073    (2012)

***

Under discussion, the authors stated “Ritual circumcision among Danish boys is linked to an overall 46–62% increase in ASD risk in the first 10 years of life, with the upper risk estimate obtained after restriction to the period with the most complete data. More strikingly, risk was 80–83% increased in the first 0–4 years of life, an increase that was restricted to infantile autism. Non-therapeutic circumcision is uncommon in Denmark outside Jewish and Muslim communities, but due to our study’s national coverage over two decades (1994–2013), findings were based on fairly solid numbers, and a series of robustness analyses confirmed the main findings. …” (End of quote) 

Again, as mentioned, the total publication is definitely well worth reading carefully.

Because I am unable to discuss and evaluate the statistical analysis in detail, I would like to invite any interested statistician to please help out.

I should however note that:

A: Circumcision preceded all forms of autism by several centuries

B. There does not seem to have been sudden worldwide increases in circumcision rates to explain the significant periodic increases in autism cases.

***

It is with appreciation that I note that the authors listed a single paragraph under “Strengths” and thirteen (13) paragraphs under “Weaknesses”.

Dr. Frisch fully disclosed his competing interests and Mr. Simonsen had none to declare.

The authors obtained approval for the study from the Danish Data Protection Agency.

The study was peer reviewed and the reviewers’ names were published.

  *****

In closing, no one has recently heard much about Autism/ASD from NCBDDD Director Boyle.

Her review and comments of this new and important research from a source the CDC has always trusted and quoted will certainly be appropriate and appreciated.

Dr. Boyle’s input is relatively more urgently needed now because the above-discussed recent Danish Autism publication has been just cited as Reference 19 in “Foreskin Morbidity in Uncircumcised Males”, a report in the May 2016 Issue of PEDIATRICS.

 

Falmouth, Massachusetts

May 5, 2016

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