Sep 13 2010

The Long Awaited CDC Trial on Thimerosal and Autism

We can add one more study to the pile of evidence showing no association between exposure to thimerosal (a mercury-based vaccine preservative) and autism. The article: Prenatal and Infant Exposure to Thimerosal From Vaccines and Immunoglobulins and Risk of Autism, is published in the latest issue of Pediatrics, and shows no association between prenatal and infant exposure to thimerosal and three forms of autism – autism, autism spectrum disorder, and regressive autism.

No one study can ever be definitive, but now we have a large body of evidence from multiple studies showing a lack of association between thimerosal and autism. This won’t stop the dedicated anti-vaccinationists and mercury militia from continuing their anti-vaccine propaganda, but hopefully it will further reassure those who actually care about the science.

Background

This has been a long and complex story, so let me review some of the background. Diagnosis rates of ASD have been climbing for the last 20 years, prompting some to search for an environmental cause. The existing anti-vaccine community, not surprisingly, blamed vaccines. This was given a tremendous boost by the now-discredited study by Andrew Wakefield concerning MMR (which never contained thimerosal) and autism. When the evidence was going against MMR as a cause, attention turned to thimerosal in some vaccines. This notion was popularized by journalist David Kirby in his book, Evidence of Harm.

However, this important premise of a correlation – rising ASD rates – is not as simple as the anti-vaccine crowd assumes. In fact there have been many studies of autism prevalence and the consensus at this time is that most of the increase in ASD is due to a broadened diagnosis, diagnostic substitution, and increased surveillance. There may be a small real increase, but most if not all of the increase is an artifact of diagnosis, not a real increase. (Side note – I have written about this topic many times before, and the links I will provide for background are to my previous reviews and summaries, not the original research. But of course, the links to the original research can be found in my prior articles.)

As further support of this a recent NHS study found a consistent prevalence of autism of about 1% in all age groups. If autism rates were truly increasing we would expect a lower prevalence in older age groups, but that is not what they found.

Another line of evidence is the younger and younger identification of signs of autism. Formal diagnosis is often made around 2-3 years old, after many vaccines are given. But numerous recent studies have documented signs of autism as young as 6 months of age. This makes it difficult to blame vaccines given after 6 months.

Holdouts for vaccines as an important contributor to autism rates have pointed to prenatal vaccines given to the mother, but a study finds no correlation there either.

Where the “mercury militia” gains their only support is from the fact that mercury is indeed a known toxin, and a neurotoxin. However, there are still problems with the notion that mercury toxicity from thimerosal causes any neurological damage or specifically contributes to autism rates. The first is that thimerosal contains ethylmercury, which is not nearly as toxic as methylmercury, the form that is found in fish and other environmental sources. Second, the doses given is vaccines is well  below safety limits. Anti-vaccinationists argue that the cumulative dose is high enough to cause damage, but there is no evidence for this. What there is evidence for is the fact that infants excrete mercury very efficiently, and therefore likely clear their mercury load after one vaccine and before the next, so it does not accumulate. And finally – mercury toxicity does not resemble autism (despite the false claims of the anti-vaccine crowd).

Another line of evidence that presents problems for the vaccine hypothesis of autism is the massive and growing evidence that autism is dominantly a genetic (not environmental) disorder. Of course, genes interact with the environment, and there may be environmental factors, but the dominant factor is genetic.

In addition to the multiple independent lines of evidence all arguing against a link between vaccines in general and thimerosal in particular to ASD, there is the ecological and epidemiological evidence which looks specifically at if there is any correlation between thimerosal exposure and risk of autism. Here the answer is a clear – no. There have been multiple such studies in multiple countries (summarized here) showing no correlation.

In addition, A recent Italian study showed no link between the amount of thimerosal exposure and autism risk. Another study showed no correlation between blood levels of mercury and risk of autism.

But the most compelling evidence against a link came from the removal of thimerosal from the routine childhood vaccine schedule in the US. By the end of 2002 all thimerosal, except for insignificant trace amounts, was removed from all vaccines given routinely to children. Only some flu vaccines still contained a small amount of thimerosal, but this is an optional vaccine with thimerosal-free options. The result was a dramatic plummet of thimerosal exposure in the US childhood population. If thimerosal were a significant contributor to autism incidence then we should have also seen a plummet in autism rates. David Kirby predicted this, and the anti-vaccine movement agreed. They gloated about the day they would be proven undeniably correct.

But now it has been 8 years – and autism rates continue to rise at the same rate, without so much as a blip. They tried to move the goalposts for a while, and make some desperate arguments to rescue their failed predictions, but there is no hope. There is no rational conclusion remaining except that thimerosal in vaccines is not a measurable contributor to autism rates.

The CDC Studies

Three years ago I wrote about a CDC study that looked at thimerosal exposure and 42 different neurological outcomes (but not autism). What they found was that there were a few scores that were worse among those exposed to more thimerosal, but there were also a few scores that were better. There was a random distribution of slight positive and negative effects that essentially average out to no net effect. It’s all just noise.

The bottom line is that this study showed no correlation between thimerosal exposure and adverse neurological outcomes.

At the time we were promised a follow up study of similar design that looked specifically at autism – and now, after a three year wait, we finally have those results. This is a case-control observational study that looked at managed care organization (MCO) members for their history of vaccination, including pre-natal vaccination, as well as exposure to thimerosal through immunoglobulins. They correlated thimerosal exposure from these sources to later diagnosis with autism, autism spectrum disorder, and regressive autism. They found:

RESULTS: There were no findings of increased risk for any of the 3 ASD outcomes. The adjusted odds ratios (95% confidence intervals) for ASD associated with a 2-SD increase in ethylmercury exposure were 1.12 (0.83–1.51) for prenatal exposure, 0.88 (0.62–1.26) for exposure from birth to 1 month, 0.60 (0.36–0.99) for exposure from birth to 7 months, and 0.60 (0.32– 0.97) for exposure from birth to 20 months.
CONCLUSIONS: In our study of MCO members, prenatal and early-life exposure to ethylmercury from thimerosal-containing vaccines and immunoglobulin preparations was not related to increased risk of ASDs.

The strengths of this study are the large numbers, the thorough assessment of ethylmercury exposure, and the confirmation of diagnosis. However, this is not a perfect study – it suffers from the limitations of observations studies, as the authors point out in their discussion. The primary weakness was the fact that of 771 potential case-children and 2760 controls they ended up with 246 cases-children and 752 controls. Around 12% were not eligible for various reasons, and the rest were not able to participate for various reasons (because they could not be located, for example), but most of the drop out was simply because potential subjects did not wish to participate.

This high percentage not participating in the study opens the door wide for bias in the final results. The authors were fairly thorough in exploring possible sources of bias from this fact. They found that study participants did not differ significantly from those not participating in various key aspects – such as having an older sibling with autism. Also most case-children were diagnosed with autism after their infant vaccines, so this unlikely to have affected vaccination rate.

But of course it is always possible for there to be unknown confounding factors biasing the results.  A protective effect from thimerosal is biologically implausible, so these results are due to either random chance or some bias in reporting or participation that is not apparent.

Even still, if there were a significant causal effect from thimerosal it should be apparent in this type of study, and it wasn’t.

Conclusion

No one study, especially an observational study, is ever very compelling. I don’t think this one new study changes the scientific picture of vaccines or thimerosal and autism. But it is one more study that fails to show any correlation between thimerosal exposure and risk of developing autism or ASD. This comes on top of multiple independent lines of evidence all pointing away from the notion that vaccines or thimerosal are a significant cause of autism.

The scientific community is likely to see this as further confirmation of a lack of association between vaccines and autism – just one more piece of the big picture. The anti-vaccine community is likely to dismiss it as either hopelessly flawed or as part of the conspiracy. In other words – this study is unlikely to change anyone’s mind on this issue.

Share

28 responses so far

28 Responses to “The Long Awaited CDC Trial on Thimerosal and Autism”

  1. Turkish01on 13 Sep 2010 at 10:06 am

    Study after study confirms the lack of a connection between vaccines and autism, and yet some judge still gives 1.5 million and 500K per year to the family of Hannah Poling.

    Five hundred thousand dollars per year… Are they planning to start their own space program?

  2. Joshua DeWaldon 13 Sep 2010 at 12:09 pm

    If I’m reading it right, the part that the AoA folks are going to key in on is that there seems to be some slightly elevated risk for prenatal exposure.

    The obvious response being, that there actually seems to be some “benefit” to ethylmercury exposure. Can’t imagine a real reason for that, though this is the 2nd study I think that seems to find a reverse correlation to thimerosal and autism.

  3. HHCon 13 Sep 2010 at 12:14 pm

    Popular children’s books and recent movies, Alice and Wonderland and Through the Looking Glass, have Mad Hatter characters which show off mecury poisoning as an art form. The neurological effects, confused speech and distorted vision from mercury poisoning were a hatter’s hazard.

    Danbury, Connecticut in the 19th century, was the hat making capital of the world. Mercury contaminants continue to be found in the soil and river sediments. Scarey bedtime stories and environment hazards lead to much public fear.

  4. ChrisHon 13 Sep 2010 at 12:15 pm

    Turkish01, Hannah Poling does not have autism. She has a mitochondrial disorder and did get encephalopathy from a fever a few days after catch-up vaccines. Because encephalopathy is a table injury for vaccines the family was awarded funds for her care. Don’t believe everything you read in the news.

  5. Ufoon 13 Sep 2010 at 12:53 pm

    Regarding vaccines and autism, this is a big one:

    http://www.cbsnews.com/8301-31727_162-20015982-10391695.html

    “Family to Receive $1.5M+ in First-Ever Vaccine-Autism Court Award”

    “In acknowledging Hannah’s injuries, the government said vaccines aggravated an unknown mitochondrial disorder Hannah had which didn’t “cause” her autism, but “resulted” in it. It’s unknown how many other children have similar undiagnosed mitochondrial disorder.”

    I’d like to understand this case much better.

    Best,

    Ufo

  6. Ufoon 13 Sep 2010 at 12:55 pm

    How clever of me not to read the other comments before posting. Anyways, I’d still like to understand the case better.

    Best,

    Ufo

  7. HHCon 13 Sep 2010 at 1:52 pm

    Ufo, Good link. Based on the federal legal document, the case has a reimbursement of the Medicaid lien of $7,821.81, a lump sum payment to petitioners of $140,109.67, and a lump sum lifecare plan through insurance annuity contracts of $1,507,284.67, payable to the legal guardians or conservators of the child’s estate.

  8. lizditzon 13 Sep 2010 at 2:25 pm

    Ufo, on the Poling case, see which has a link to the full decision:

    http://blogs.nature.com/news/thegreatbeyond/2010/09/us_vaccine_payout_provokes_con.html

    As is my habit, I’m keeping a list of blog & news reactions to the Price et al. paper:

    http://lizditz.typepad.com/i_speak_of_dreams/2010/09/important-new-paper-again-maybe-finally-no-link-between-vaccination-and-thimerosal-in-vaccines-not-c.html

    Finally, Sullivan has posted some questions and answers from the study author:

    http://leftbrainrightbrain.co.uk/2010/09/questions-and-answers-with-the-thimerosal-autism-study-author/

  9. halincohon 13 Sep 2010 at 2:30 pm

    Upon revieweing mitochondrial disease and autism in Pub Med, there seems to be an increase in prevelance in patients with mitochondrial diseases. Thus how does one know if the vaccines played any role in this case or not without a double blind randomize study?

    The article:

    Autism and mitochondrial disease.
    Haas RH.

    Department of Neurosciences, UCSD Mitochondrial and Metabolic Disease Center, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA. rhaas@ucsd.edu

    Abstract
    Autism spectrum disorder (ASD) as defined by the revised Diagnostic and Statistical Manual of Mental Disorders: DSM IVTR criteria (American Psychiatric Association [2000] Washington, DC: American Psychiatric Publishing) as impairment before the age of 3 in language development and socialization with the development of repetitive behaviors, appears to be increased in incidence and prevalence. Similarly, mitochondrial disorders are increasingly recognized. Although overlap between these disorders is to be expected, accumulating clinical, genetic, and biochemical evidence suggests that mitochondrial dysfunction in ASD is more commonly seen than expected. Some patients with ASD phenotypes clearly have genetic-based primary mitochondrial disease. This review will examine the data linking autism and mitochondria.

    PMID: 20818729 [PubMed - in process]

    Steve, is there even meta-analysis evidence for an increase in occurence between those with mitochondrial disease who have been vaccinated and those who have not? I imagine this sample size would be pretty small to begin with. Is there ANY plausable cause that would increase the risk?

  10. SquirrelEliteon 13 Sep 2010 at 4:05 pm

    For a little background on the Hannah Poling case, I responded to halincoh by posting links to other blog articles on the Organic Food thread.

    Check here:

    http://www.theness.com/neurologicablog/?p=2285&cpage=3#comment-25982

  11. daedalus2uon 14 Sep 2010 at 8:12 am

    The mitochondrial disorder that Hannah Poling has (it isn’t clear if it is a disorder or just a variation) she got from her mother who has the exact same mitochondiral DNA difference.

    It is not possible for a vaccine or any environmental effect to cause a mitochondrial DNA change in a multi-cellular organism because daughter cells inherit their mitochondria from their parent cells. Each cell has hundreds or thousands of mitochondria.

    A disruption to mitochondrial DNA happens at a specific site on a single strand of DNA. DNA strands that descended from that parent DNA strand will have the same DNA difference.

    The chances that another DNA strand will acquire the same DNA change in the same location via a mutagenic effect is approximately 1/(number of places in the DNA strand a mutation could occur). There are about 15,000 base pairs in, so the chances of a new mutation happening in the same place in a second DNA strand are 1/(15,000) or 0.000007. Each cell has hundreds to thousands of mitochondria, so for all the mitochondria in a cell to get the same DNA change would be (0.000007)^100 (for a small cell) or (0.000007)^10000 for a large cell. For every cell in an individual to get the same DNA change due to a mutation would be ((0.000007)^1000)^1,000,000,000,000.

    There isn’t enough paper in the universe to write out that number not using scientific notation.

  12. Science Momon 14 Sep 2010 at 11:45 am

    Having a conversation with an anti-vaxxer elsewhere, this appears to be their rebuttal to the Price et al. Thimerosal Autism study: http://www.vaccinationcouncil.org/vaccination/articles/the-avalanche-of-new-mercury-autism-studies.html

  13. wfron 14 Sep 2010 at 1:40 pm

    I’d like to know the actual harm that is caused by vaccines. I’m talking about the one-in-a-zillion chance that a vaccination will cause a real ill effect. There must be science on this. Where can I read about it?

  14. halincohon 14 Sep 2010 at 2:45 pm

    @ daedalus

    Yes, of course the vaccine can’t CAUSE a mitochondrial disorder. My question is in a population of those with mitochondrial disorders ( a population as noted above seem to have a higher incidence of autism ) does getting vaccinated specifically increase the risk for THIS population? My immediate thinking is no. I can’t think of a plausible interaction, but without studies being done, then how can anyone scientifically think that the vaccine caused autism in this unfortunate little girl? Without studies in this population one can’t say anything confirmatory. Legal decisions should be based on science. Alas, they are usually not.

  15. ChrisHon 14 Sep 2010 at 3:33 pm

    My question is in a population of those with mitochondrial disorders ( a population as noted above seem to have a higher incidence of autism ) does getting vaccinated specifically increase the risk for THIS population?

    No.

    Some extra reading:
    Mitochondrial Disorders and Autism
    and
    Vaccines and Autism Revisited — The Hannah Poling Case

    From the latter:

    First, whereas it is clear that natural infections can exacerbate symptoms of encephalopathy in patients with mitochondrial enzyme deficiencies, no clear evidence exists that vaccines cause similar exacerbations. Indeed, because children with such deficiencies are particularly susceptible to infections, it is recommended that they receive all vaccines.

  16. daedalus2uon 14 Sep 2010 at 6:34 pm

    halincoh, the most characteristic physical feature of autistic individuals is a larger number of minicolumns. That number if fixed during the first trimester in utero. A vaccine sometime later can’t change that number.

    There are known teratogens that do cause autism, valproate and thalidomide. They only cause autism during narrow widows of time during the first trimester in utero.

    There is no plausible mechanism by which a vaccine could change the brain and produce more minicolumns other than magic.

    No one does think “scientifically” that vaccines caused autism in Hannah Poling. The court ruling was not a scientific finding and the court didn’t rule that she has autism (she doesn’t), or that a vaccine caused her to have the autism she doesn’t have.

    Dr Poling’s co-authors in the study that described his daughter were quite upset that they were not told of his conflict of interest in the case. They didn’t realize the paper would be used as “evidence” in the lawsuit in front of the vaccine court. The editor of the journal was quite upset too. People who read the article and relied on the author’s non-disclosure of conflicts of interest were upset too.

    I am still upset about it because it damages the scientific literature and makes autism research more difficult by throwing up red herrings. I see it as using the scientific literature to “game” the legal system to get a lot of money. One is certainly free to take that impression given how Dr Poling went in front of TV and generated PR for the anti-vaccine movement.

  17. halincohon 15 Sep 2010 at 1:40 am

    Like I said – NO plausibility.

    But law has nothing to do with evidence. It has to do with how one tells a story and how well the characters are portrayed.

    I have been involved in one malpractice case over my 19 year career. There was no case. I did nothing wrong. The family, who never met me wanted to settle for money. Sadly, it was simply about money. Our experts were excellent. Their experts had to be uncovered from rocks. Ours: physicians in their prime, excellent communicators. Their’s: retired ,very old, bumbling. The bailiff came over to me as the jury broke for lunch before coming to a decision and said, ” you didn’t do anything wrong, Honey.” And 30 minutes later, the jury, while still digesting their meal dismissed the case.

    But before I was found innocent of any wrong doing, the lawyer, after the bailiff spoke to me said, ” don’t get too high if we win or too low if we lose.” I said incredulously, ” lose?” I said ,” but I did nothing wrong and we presented an excellent case.” The lawyer said, ” it doesn’t matter … what matters is IF THEY LIKE YOU.”

    He was dead serious. I’ve spoken to other lawyers since this was said to me. And all agree. What matters is if the jury likes you, your lawyer, and your experts.

    We, here, in science based medicine land, can discuss plausibility and evidence and it matters not, not to lawyers, and definitely not to a jury.

    And this is why the plaintiff won the case.

    Sad.

  18. Dawnon 15 Sep 2010 at 11:19 am

    @wfr: I don’t think there is one, unified place where you can find the actual harm that is caused by vaccines. I’m talking about the one-in-a-zillion chance that a vaccination will cause a real ill effect. There must be science on this.

    If you go to the CDC website you can search on vaccine side effects and possible injuries:

    http://www.cdc.gov/vaccinesafety/index.html

    and there is also a link there to the VAERS database where all vaccine injuries are supposed to be reported. Unfortunately, since the VAERS database is self-reporting and not really reviewed its accuracy is only fair (one person notoriously reported that a vaccine turned his daughter into Wonder Woman…the man and his daugher don’t even live in the US, nor was the report booted from the system as being improbable!).

    The Vaccine Court has a list of Table Injuries (a table of known injuries from vaccines) that, if you go to the court with one of these documented injuries, you will be reimbursed without issues. Hannah Poling was actually reimbursed based on the Table Injuries; encephalitis is on the table which is why her case was “settled” without going through the special masters. You can search for how many cases are in the files with specific issues and see if they were settled and what was paid.

    I don’t know if this answers your question. If anyone knows of a site that will give what wfr is looking for, please add on!

  19. daedalus2uon 15 Sep 2010 at 12:30 pm

    The Hannah Poling case was not before a jury but before special masters, who are judges with the technical expertise to understand the medical issues involved.

  20. SquirrelEliteon 15 Sep 2010 at 1:04 pm

    HRSA also keeps a regularly updated table of statistics on the National Vaccine Injury Compensation Program (NVICP).

    http://www.hrsa.gov/vaccinecompensation/statistics_report.htm#statistics_report

    Since this represents claims that have actually been filed and are somewhere in the process of being evaluated and either compensated or dismissed, it has somewhat more statistical and historical validity than the VAERS numbers.

    Also, I noted that they have been working for two years on a project

    to review the epidemiological, clinical, and biological evidence regarding adverse health events associated with specific vaccines covered by the Vaccine Injury Compensation Program.

    The vaccines to be reviewed are

    * varicella vaccines,
    * influenza vaccines,
    * hepatitis B vaccine,
    * human papillomavirus virus vaccines,
    * hepatitis A vaccines,
    * meningococcal vaccines,
    * measles-mumps rubella vaccines, and
    * diphtheria, tetanus, pertussis vaccines

    The committee will author a consensus report with conclusions on the evidence bearing on causality and the evidence regarding the biological mechanisms that underlie specific theories for how a specific vaccine is related to a specific adverse event.

    Since the first meeting was in April 2009, perhaps the committee will finish the project and issue a report next year. That should be very interesting.

  21. Dawnon 15 Sep 2010 at 1:40 pm

    @daedalus2u: I was under the impression that since the Poling case was handled as a table injury it didn’t go before a special master? Or do they evaluate table injuries too? I’m not that up on the Vaccine court.

    @SquirrelElite: that’s very interesting. I’d never heard of that project. Thanks for the info. And thanks for the hrsa info. I didn’t know about that, either. That’s why I love these blogs; I learn so much!

  22. SquirrelEliteon 15 Sep 2010 at 2:53 pm

    @Dawn,

    The Hannah Poling case has been discussed several times on this and other blogs.

    I provided a link to some links in my Sept 13 comment.

    It may have gone to a special master because of the autism claim, but it was compensated instead because she developed encephalopathy and that is already a table injury.

  23. Dawnon 15 Sep 2010 at 3:23 pm

    @SquirrelElite: That’s what I was wondering. I knew she was compensated as a table injury due to the encephalitis, but what I don’t know (and guess I phrased it badly) is if it requires a special master’s review to determine a table injury or if someone else makes that decision based on the medical record. That is something I don’t recall reading anywhere. I know the decision is available, which would, I assume, let me know who made it – a special master or someone else – but I can’t seem to get my computer to access it….our IT people block the weirdest things.

  24. Dawnon 15 Sep 2010 at 3:27 pm

    And, guess I should clarify – what I am wondering is really 2 things:

    do special masters make the decision for all table injuries or does someone else – who determines whether something is a table injury or not?

    and

    due to the “autism-like” issues, was the Poling decision made by a special master who used the table for the appropriate encephalitis claim or did someone else make the decision because it was determined to be a table injury?

  25. ChrisHon 15 Sep 2010 at 3:35 pm

    This document shows that the Special Master made the judgment.

    The difference is that this was not part of the Autism Omnibus proceedings, as it is not listed here.

  26. SquirrelEliteon 15 Sep 2010 at 3:57 pm

    For more background on the Hannah Poling case, Dr Gorski’s article from 2008 in SBM is also a good source:

    http://www.sciencebasedmedicine.org/?p=66#more-66

    Originally, Hannah’s case was part of the Autism Omnibus proceedings. But, it was pulled out for a separate decision because of her diagnosed mitochondrial disorder.

  27. halincohon 16 Sep 2010 at 7:39 pm

    @ daedalus2u

    Then I’m completedly dumfounded.

  28. daedalus2uon 16 Sep 2010 at 9:35 pm

    The Hannah Poling settlement had nothing to do with autism. It was about encephalopathy which is sometimes caused by the immune system stimulation of vaccines, particularly in people who are especially sensitive to such things, such as people with mitochondrial disorders (which HP may or may not have, she does have the variation, but that may not be adverse, it is in one of the protein synthesizing molecules (as I remember), not one of the proteins in the respiration chain).

    The report the settlement was based on was illegally leaked to the media. I think that the people who wrote the report would never have used “autism-like” if they knew it was going to be latched onto by the media and the anti-vaccine people.

    I think the special masters have to sign off on the decision, but it is a pro forma decision if it is a table injury, which encephalopathy is. The only reason it took so long was because the Polings lawyer tried to use this encephalopathy as an autism test case (when it wasn’t). That is malpractice by the lawyers.

Trackback URI | Comments RSS

Leave a Reply

You must be logged in to post a comment.