Teresa Binstock
Researcher in Developmental & Behavioral Neuroanatomy
January 31, 2010
In 2009, Samar H. Ibrahim and colleagues at Mayo Clinic published a
study summarizing the researchers' glimpse at gastrointestinal
pathologies in children with and without autism (1). Question arise:
Did the study's methodology have one or more major weaknesses? How
valid are the group's findings and interpretations? Is the researchers'
article generating misleading impressions?
The Ibrahim et al study was published online on July 27, 2009, in the
journal "Pediatrics". On July 28th, 2009, an initial critique was
shared by autism parent and physician Bryan Jepson, M.D., author of a
fully citationed but readable text Changing
the Course of Autism.
In regard to the Ibrahim et al study, Dr. Jepson wrote:
There are several
problems with the Mayo study.
First, it is retrospective which means that it relies on how well the
physicians record the symptoms (even if the access to records is
great). It has been shown in reviews of other studies in autism
comparing retrospective to prospective designs, that many physicians
simply ignore the GI symptoms in children with autism. There may be
many reasons for this, including that they don’t believe that their GI
symptoms are relevant to the presenting complaint, there is difficulty
getting a history from a non-verbal child (i.e. the kids may not
complain), the symptoms present differently from other kids (they don’t
describe heartburn for reflex; or the stools are only mushy, not watery
so they don’t consider it “diarrhea”; or their stools are infrequent
and hard to pass but they come out loose so they don’t consider this
constipation; or they don’t look at or measure the abdomen and since
the kids don’t complain, they don’t record abdominal bloating). When
studies have been done that look prospectively at GI symptoms in autism
with specific targeted questionnaires, they have always shown a
difference between kids with autism and controls.
Second and
more importantly, they [Ibrahim et al] measure a cumulative incidence.
That means that if any of the kids had diarrhea recorded in their
chart, even if only once, it would be counted. That is why they have
such high incidence in both kids with autism and normal kids. It is
very common to have one or two bouts with constipation or diarrhea over
your entire childhood. The important difference is how chronic it is,
not if you’ve ever had it. So having a viral illness with diarrhea
that last for a week or two was counted the same as children who may
have had chronic loose stools every day of their life. They do not
distinguish these issues in their study data.
The first and second concerns delineated by Dr. Jepson are very
important. Indeed, a Medscape reviewer, William T. Basco, Jr., MD,
FAAP, called attention to the weakness of tracking cumulative incidence
and doing so without evaluating duration or severity of a child's
gastrointestinal pathologies, writing "The authors admit that a
limitation of the study is the fact that the analyses do not account
for duration or severity of symptoms, both of which would have required
more extensive, primary data collection during each episode of
gastrointestinal symptoms compared with chart review." In other words,
in the Ibrahim study, a child who had diarrhea once for three days
would be counted the same as a child who had diarrhea for 6 months. As
physicians Jepson and Basco suggest, the child with a brief bout of
diarrhea or constipation may be physiologically very different from a
child whose intestinal pathology is prolonged.
In his review of July 28, 2009, Dr. Jepson presented three additional
concerns:
Third, they
[Ibrahim et al] did find differences in constipation and food
selectivity but they interpret this as a behavior consequence not a
physiological problem. That is their opinion. There is nothing in
their study design that would show if that is true or not true.
Fourth, they [Ibrahim et al] mentioned that very few of the autistic
children had documented Crohn’s disease, Celiac disease or enzyme
deficiency. But they don’t mention how many of the kids were worked up
for these things. If you don’t look, you won’t find it. Why not
report the number of scopes, biopsies or celiac panels? My guess is
that it is because very few of these kids were actually worked up
appropriately.
Fifth, assessing the prevalence of some of the GI symptoms in autism is
very challenging without a further workup because many of the symptoms
are subjective and require patient cooperation to get at the
diagnosis. For example, abdominal pain. If a child cannot tell you
that they are having abdominal pain, how are you going to identify it
or record it. Especially when many of the potential manifestations of
abdominal pain in autism (irritability, aggressiveness, self-injurious
behaviors, etc) are often and easily explained away as typical “autism”
behavior and a pain etiology is not further explored. How does a child
with autism who is having reflux describe that to a doctor. Unless it
is severe enough to be causing vomiting, asthma, etc , it will be
missed. Yet, neurotypical kids can describe heartburn or epigastric
discomfort and are more likely to have it diagnosed. So mild cases
will be diagnosed in neurotypical kids and only severe cased in
autistic children. This will change the prevalence numbers between the
cases and controls and it all comes down to how easy it is to obtain
the history, not the true prevalence. I suspect that if you took all
of those children, both neurotypical and controls, and scoped them,
that the level of pathology would be much, much higher in autism.
Oversights such as those inherent in the methodology, findings, and
interpretations offered by Ibrahim and colleagues - especially given
their Mayo Clinic affiliation - can be unintentionally presumed to be
authoritative and may have subserved a recent U.S. News & World
Report article, wherein obviously caring correspondent Judith Palfrey,
M.D., cited Harvard's William Barbaresi, M.D., and offered, "Recent
studies show that children with autism are at no higher risk of having
gastrointestinal problems than are children without autism." (5)
That's a major point in the critiques by doctors Jepson and Basco.
Studying incidence without including severity and duration as
co-factors can lead to misleading oversimplifications.
Dr. Palfrey also mentioned diets and autism, "I'm wondering about the
recent
news showing little evidence that special diets do any good." Here
it's important to offer a mild rebuttal. Evidence cited in reviews by
Timothy Buie, M.D., and colleagues (6-7) is consistent with at least
one other study (8) and with long-term data compiled by the Autism
Research Institute (9): according to parents of children with autism,
special diets help in ~60% of autistic children who were placed on a
restricted diet (reviewed in 10).
Conclusion: That gastrointestinal pathologies in children with autism
and other autism-spectrum disorders (ASDs) can be contemplated,
evaluated, and treated is a major step forward and, to some extent, the
study by Mayo Clinic's Samar Ibrahim and colleagues is helpful even as
its methodology was seriously flawed and its findings and conclusions
leave much to be desired. As months turn into years, the full and
possibly etiologic significance of gastrointestinal pathologies in
children with autism or one of the other ASDs will be more fully
appreciated, including a direct gut-brain-language connection (11) and
the increasingly described intestinal lymphoid hyperplasia (12-13).
Evaluating and treating autistic children's intestinal pathology has
been decreed a legitimate concern (6-7).
References:
1. Incidence of
Gastrointestinal Symptoms in Children With Autism: A Population-Based
Study
Samar H. Ibrahim, Robert G. Voigt, Slavica K. Katusic, Amy L. Weaver,
William Barbaresi.
Departments of Pediatric and Adolescent Medicine and Health Sciences
Research
Mayo Clinic, Rochester, Minnesota
Pediatrics 2009;124;680-686. Epub 2009 Jul 27.
$ http://pediatrics.aappublications.org/cgi/content/full/124/2/680
2. Changing the
Course of Autism
Bryan Jepson, M.D., with Jane Johnson.
http://www.amazon.com/Changing-Course-Autism-Scientific-Physicians/dp/1591810612
3. Critique of
Ibrahim et al 2009{cite-1
herein}
Bryan Jepson, M.D.
July 28, 2009.
Personal communication, excerpts shared with permission.
4. Do Children With
Autism Experience High Rates of Gastrointestinal
Problems?
{Review of Ibrahim et al, cite-1 herein}
William T. Basco, Jr., MD, FAAP
http://www.medscape.com/viewarticle/709656
5. What's the Story
About Gastrointestinal Problems in Kids With
Autism?
Judith Palfrey, M.D.
http://www.usnews.com/health/blogs/health-advice/2010/01/29/whats-the-story-about-gastrointestinal-problems-in-kids-with-autism
6. Evaluation,
Diagnosis, and Treatment of Gastrointestinal Disorders in Individuals
With ASDs: A Consensus Report
Buie T et al.
Pediatrics 2010;125:S1–S18.
http://pediatrics.aappublications.org/cgi/content/full/125/Supplement_1/S1
7. Recommendations
for Evaluation and Treatment of Common Gastrointestinal Problems in
Children With ASDs
Buie T et al.
Pediatrics 2010;125:S19–S29
http://pediatrics.aappublications.org/cgi/content/full/125/Supplement_1/S19
8. A randomised,
controlled study of dietary intervention in autistic
syndromes
Knivsberg AM, Reichelt KL, Høien T, Nødland M.
Nutr Neurosci. 2002 Sep;5(4):251-61.
9. ARI Parent
Ratings: For several decades, the
Autism Research Institute has been creating a database comprised of
parental reports of what treatments worked (for a specific child), what
treatments didn't work; which set the child back, which didn't seem to
have any effect. The data include pharmaceuticals, supplements, and
diets. In each line-item within the data presentation, consider the
ratio (per treatment) of got-better/got-worse.
Parent Ratings of Behavorial Effects of
Biomedical Interventions
http://www.autism.com/treatable/form34qr.htm
10. Gastrointestinal
pathologies in ASD children: new autism-gastro stance by
AAP
Teresa Binstock; January 05, 2010
11. Anterior insular
cortex: linking intestinal pathology and brain function in
autism-spectrum subgroups.
Binstock T.
Med Hypotheses. 2001 Dec;57(6):714-7.
12. Ileal-lymphoid-nodular hyperplasia, non-specific
colitis, and pervasive developmental disorder in
children
Wakefield AJ et al.
Lancet. 1998 Feb 28;351(9103):637-41.
13. Clinical
Presentation and Histologic Findings at Ileocolonoscopy in Children
with Autistic Spectrum Disorder and Chronic Gastrointestinal
Symptoms
Arthur Krigsman, Marvin Boris, Allan Goldblatt and Carol Stott
Autism Insights 2010:2 1-11; 27 Jan 2010
http://www.la-press.com/clinical-presentation-and-histologic-findings-at-ileocolonoscopy-in-ch-a1816
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