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AGE OF AUTISM: OUR STORY SO FAR

DR. ANDREW WAKEFIELD'S RESPONSE TO BAIRD G. ET AL

Dr_wakefield_2Thank you to Dr. Andrew Wakefield, of Thoughtful House Center for Children for sending us this important piece:

Response to Baird G. et al. Measles vaccination and antibody response in autism spectrum disorders. Archives of Disease in Childhood. Published 5th February 2008.

In a case-control study of 10 to 12-year-old children with either autism, special-educational needs, or normal development, the authors examined measles-antibody responses (plaque reduction neutralization assay) and the presence of measles virus in peripheral blood mononuclear cells (reverse transcriptase polymerase chain reaction). The study apparently sought to identify autistic children relevant to the original MMR/autism hypothesis, i.e., those who regressed and those with bowel symptoms.

The study is severely limited by case definition in the context of the crucial ‘possible enterocolitis’ group. For inclusion in this group they required the presence of two or more of the following five current gastrointestinal symptoms:

• current persistent diarrhea (defined as watery/loose stools three or more times per day >14 days),
• current persistent vomiting (occurring at least once per day, or more than five times per week),
• current weight loss,
• current persistent abdominal pain (3 or more episodes [frequency not specified by authors] severe enough to interfere with activity);
• current blood in stool;
plus:
• past persistent diarrhea >14 days’ duration, and excluding current constipation.

We have over the last 10 years evaluated several thousand children on the autistic spectrum who have significant gastrointestinal symptoms. Upper and lower endoscopy and surgical histology have identified mucosal inflammation in excess of 80% of these children. Almost none of these children with biopsy-proven enterocolitis would fit the criteria set out above. Firstly, these children rarely have vomiting, current weight loss (as opposed to failure to gain weight in an age-appropriate manner), or passage of blood per rectum. The requirement is thus narrowed to a child having two of two relevant symptoms – current persistent diarrhea and current abdominal pain according to their criteria, plus a past history of persistent diarrhea excluding current constipation. 

The requirement for the current presence of these symptoms, for 14 or more days continuously, shows a singular lack of understanding of the episodic, fluctuating, and alternating (e.g. diarrhea/constipation) symptom profile experienced by these children. In our experience, ASD children with histologic enterocolitis typically have 1 to 2 unformed stools per day that are very malodorous and usually contain a variety of undigested foodstuffs. This pattern alternates with that of “constipation” in which the unformed stool is passed after many days of no bowel movements at all, and with excessive straining. This group is entirely overlooked by the arbitrary criteria set forth in their paper. With respect to diarrhea and constipation, a detailed discussion of stool pattern in these children is available1 which further highlights the shortcomings of the above criteria. Moreover, the interpretation of pain as a symptom in non-verbal children, as it often manifests as self injury, aggressive outbursts, sleep disturbances, and abnormal posturing, is notoriously difficult. This interpretation requires an insight based upon the correlation of symptoms, histological findings, and response of symptoms to anti-inflammatory treatment. There is no evidence in the Baird et al. paper that these crucial factors were taken into account. This study’s inappropriate symptom criteria would explain the discordance with other reports that have revealed a high prevalence of significant gastrointestinal symptoms in general autism populations2,3.

It is surprising that Dr Peter Sullivan, a co-author on the paper, who presumably provided the above gastroenterological criteria, was not aware of the aforementioned limitations. In his role as a Defendant’s expert in the UK MMR litigation, he will have had access to the clinical records of autistic children with the relevant intestinal symptoms and biopsy-proven intestinal inflammation.

We suggest that the authors might wish to reflect on the ethical implications of setting the bar too high for the investigation of such children by ileo-colonoscopy, with the attendant risk of missing symptomatic, treatable inflammation.

Since the relevant MMR/autism children are considered to be those with regression and significant gastrointestinal symptoms, the appropriate stratification for between-group analyses of measles virus antibody levels has not been conducted; therefore the paper is difficult to interpret, adding little if anything to the issue of causation. Moreover, it is a major error to have presumed that peripheral blood mononuclear cells are a valid ‘proxy’ for gut mucosal lymphoid tissues when searching for persistent viral genetic material.

A further major problem in this study is the number of children who dropped out or who were unable to provide adequate blood samples. We know nothing about either the 735 children who were lost at stage two, or the 100 children for whom blood samples were not available. At the very least, we should be told whether the children who dropped out were likely to be representative of those who stayed in, with regard to the key issues of interest.

For reasons that will emerge in the near future, it would be of interest to know whether siblings of autistic children were included in either of the two control groups. This information is not provided.

As a general observation, this paper contributes nothing to the issue of causation, one way or another. Case definition alone is likely to have obscured the relevant group of autistic children. The study tells us nothing about what actually happened to the children at the time of exposure. We are increasingly persuaded that measuring things in blood many years down the line tells us very little about the initiating events in what is, in effect, a static (non-progressive) encephalopathy unlike, for example, subacute sclerosing panencephalitis, which is a progressive measles encephalopathy. The gut is a different matter, and analysis of mucosal tissues has been very informative, since here, in the relevant children, active ongoing, possibly progressive4, inflammation has been identified.

References.

1. Wakefield AJ. Autistic enterocolitis: is it a histopathological entity? Histopathology 2006;50:380-384.
2.  Valicenti-McDermott M, et al. Frequency of Gastrointestinal Symptoms in Children with Autistic Spectrum Disorders and Association with Family History of Autoimmune Disease. Developmental and Behavioral Pediatrics. 2006;27:128-136.
3. Horvath K, and Perman JA. Autistic disorder and gastrointestinal disease. Current Opinion in Pediatrics.  2002;14:583–587.
4. Balzola F et al. Autistic Enterocolitis in childhood: the early evidence of the later Crohn’s disease in autistic adulthood? Gastroenterology 2007;132:suppl 2, A 660. 

Competing interests
Dr Wakefield, Dr Krigsman, and Dr. Stott acted as Claimant experts in the UK MMR litigation

Comments

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Suzanne Applegate

Dr. Wakefield:
Spoke to you in 1999 (I think) when the first news broke about the autism cluster in Brick, NJ. My son Drew will be 13 in April 08. Since 2 years of age, he has had a limited gluten and casein diet - pasta and Ovaltime make up the mainstay of his nutrition. Thankfully, he has grown strong and continues to be verbal and very social. By the grace of God he is beautiful my situation is manageable. In some ways he continues to make progress. I just wanted to thank you for taking my phone call at your UK location that morning in 1999. I think about your needed determination whenever I see your articles and work on posted on the internet. Fight the good fight....we all know that you are right...thank you for helping me along my autism journey. Drew is almost 13 and I have not done any gastoenterological interventions, I just want to know...is it too late? Maybe someone can email if you have a similar situation. My son eats a steady diet of gluten and casein and of complains of stomach aches a few times per week (of course).

Suzanne Applegate - NJ Autism Mother - Don't tell me childhood vaccines don't cause Autism - Where's the science?

Raymond Gallup

Thank you very much Dr. Wakefield and Age of Autism.

These people like Baird G et al are paid by the PharmaNazis to put out their pro-vaccine propaganda.
Hired Hessians!!!!!!

Raymond Gallup

Teresa Conrick

Yes, thank you Dr. Wakefield!

Your years of real research, pertinent data, and targeted treatments have been a blessing for the autism community. Much gratitude for your continual scrutiny of these "bullshit" studies and your passion in helping our sick children.

Teresa Conrick

Sandra

Yes, thank you Dr. Wakefield and Age of Autism! I am so thankful that my child is on the road to recovery as well. Also, for the record, I don't think Age of Autism is "sensational" or "negative" whatsoever despite what some commenters say. People who write things such as this contribute nothing. Thanks you again Age of Autism and all the wonderful people who do contribute so much to help the children.

Lisa

Dear Dr. Wakefield,

Thank you for your courage. Thank you for looking for answers to a serious problem that hurts many. Thank you for not walking away from our families - no matter HOW MANY AND BIG the pressure became. Thank you for listening to parents. Thank you for finding answers.

Andy - you are a hero. You are courageous. Thank you.

Lisa - Jeffs mom and hundreds of thousands of kids like him

Mark

As always, Andy, thanks for your thoughtful commentary and all the work you do on behalf of our children.

As Andy's commentary shows yet again, this paper from Baird et al is another part of a disinformation campaign designed to confuse and obscure the issues in autism and to undermine (with hostile rather than scientific intent) some serious and troubling evidence regarding the biology and caus of autism. If someone really wanted to test the evidence on what Andy has called "autistic enterocolits", does it really make sense to design an experiment like this? And when a sloppy study design yields a negative results, does it really deserve any kind of press attention? Does this new press flurry contribute anything more than another bit propaganda to add to the "information cascade" designed to defend potentially unsafe products? And does this pattern of misinformation and propaganda does anything to promote confidence among parents in the integrity of the broader scientific entreprise?

The answer to all these questions, of course, is a resounding no.

Which leads one to ask, why is it Andy who is on trial defending his license to practice medicine?

Gatogorra

If it hadn't been for Dr. Wakefield's work, our kids wouldn't be recovering. I always think of him, the price he's paying for truth and for the sakes of all our children when I hear the Indigo Girl's song "Galileo".

Theresa Cedillo

Thank you Dr. Wakefield and Age of Autism!

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