For those that are interersted; Wakefield's response to the paper hope it's cut and pasted ok:
"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 progressive[AV1] 4, 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.