FW: A Closer Look at Fombonne's Non-Epidemic of Autism/ Chromosome 16

[Guest guest]

A Closer Look at Fombonne's Non-Epidemic of Autism/ Chromosome

16

FEAT DAILY NEWSLETTER Sacramento, California http://www.feat.org

" Healing Autism: No Finer a Cause on the Planet "

______________________________________________________

February 8, 2001 Search www.feat.org/search/news.asp

Also: On the Short Arm of Chromosome 16

A Closer Look at Fombonne’s Non-Epidemic of Autism

[Mark F. Blaxil is the father of a, near five years old and

diagnosed with PDD (at age three).]

Fombonne, in a recent letter to the journal Pediatrics that

formed the basis for a story in Reuters, claims that there is no epidemic of

autism, and argues that the " debate on the hypothesis of a secular increase

in rates of autism would benefit from a clear recognition of the

methodologic limitations of existing data. " Instead, Fombonne suggests that

we dismiss the results of numerous epidemiological studies of autism--over

forty of them in the last four decades--in the face of newer studies

demonstrating that the prevalence of autism " had clearly been underestimated

in the past. "

Fombonne's views on this subject are more important than those of the

average scientist. He is the author of two autism prevalence studies in

France (1,2) and has published two exhaustive reviews of the autism

epidemiology literature (3,4) in the last three years. He has a deeper

knowledge of the field than all but a handful of academics. So it is both

extremely important, and a bit ironic, that Fombonne argues to dismiss the

research that he has studied so carefully and start from scratch in

understanding this disorder.

Rather than accepting Fombonne's statements in Pediatrics, as those

unfamiliar with his writing might be inclined to do, I would argue that

Fombonne's opinions reflect deep confusion. His statements directly

contradict conclusions he reached as late as 1999. And his most recent

opinions are based on no research and no facts. They represent a misguided

attempt to avoid the consequence of a finding of increasing incidence: i.e.,

that autism is a disorder triggered by environmental factors and is not

genetically pre-determined. To understand the desperation in Fombonne's

reasoning, one must first understand how strongly his opinions have been

expressed and how they have changed over time.

In his original review article from 1998 (1), Fombonne made strong

statements about the time trends in autism prevalence. He asserted that " the

best available estimate " for the prevalence of autism was 5.0 per 10,000.

Further, he argued that although " the six surveys with prevalence

rates over 6 per 10,000 were all published since 1987; the prevalence rate

and year of publication [emphasis added] was, however, insignificant. " This

was a critical finding, but based on a highly flawed analysis. Fombonne made

three critical errors in reaching his conclusion.

1. Using the wrong measure of time. The date of publication has only

incidental relevance to the question of increasing rates of autism. The

scientifically relevant measure of time is the time of birth of the

populations studied. To determine if autism is increasing, Fombonne should

have analyzed the prevalence rates of autism in children born in different

time periods. Measuring time based on dates of publication fails to account

for basic differences in study design (e.g., studying only seven year olds

versus studying all children under eighteen) not to mention the variable

time delays between analysis and publication. Using year of birth as the

time measure reveals unmistakable increases over time in rates of autism,

which have approached 100 per 10,000 (or 1%) in the most recent studies.

2. Mixing geographies. Fombonne's analysis does not take into account

the possibility of structural differences in time trends of prevalence in

different country environments. Japan, for example, had the highest reported

rates of autism in the world among children born in the 1960s and 70s. Not

surprisingly, perhaps, Japan was also dealing with severe industrial

pollution problems in that period, including the notorious episodes of

methyl mercury poisoning in Minimata(1956) and Niigata (1965). Comparing

rates of autism in Japan with those of, say, the state of Utah makes little

sense. In addition, mixing geographies with different public health policies

will also obscure the hypothesized relationships between vaccinations and

autism.

In this regard, the Japanese case is also instructive. Japanese

incidence of autism has never risen above 16 per 10,000, the highest rate of

the 1970s cohorts, despite widespread reports of increases in other

countries. Japan has also banned the controversial MMR vaccine and never

introduced mandatory hepatitis B vaccinations at birth. By ignoring the

differences in autism rates and trends in those rates across geographies,

Fombonne thus obscures important etiological clues.

3. Selecting the geographies that support his biases. By 1999 (4),

Fombonne had begun to consider the possibility of using the time of birth

and not the time of publication to assess time trends of autism prevalence.

But in this second review, Fombonne selected France as the basis for his

analysis.

Perhaps unsurprisingly, he argued that the " French surveys...were not

suggestive of increasing rates in the most recent cohorts. " Based on this

sample of a single country, Fombonne concluded--after dismissing similar

data from Sweden showing a rising trend for methodological reasons--that the

" available epidemiological evidence does not therefore suggest that the

incidence of autism has increased, and several other reasons could easily

account for an artefactual impression of an increase " (4).

Indeed, based on the French data, one would conclude that autism is

neither a serious problem (the reported rates are relatively low, well below

10, per 10,000) nor increasing (the rates appeared to decline between 1975

and 1985, the most recent birth cohorts studied). Yet Fombonne does not

bother to compare public health policies in France (which suspended

hepatitis B and precedes MMR vaccines with monovalent measles, thereby

eliminating the hypothesized risk that concurrent mumps and measles vaccines

may reduce a child's ability to clear the measles virus and thus allow

chronic gatrointestinal infection) to those of other countries in which

clear increases have been reported.

These are all serious errors and lead Fombonne to dangerously flawed

conclusions.

But now, faced with the onslaught of studies suggesting dramatically

higher rates of autism, Fombonne has retreated to a different argument.

Autism rates still remain constant, in his view, however at a much higher

level than previously thought. In making this shift, Fombonne dismisses

dozens of painstaking studies performed by his fellow researchers because of

" methodologic limitations. " He also attempts to dismiss the recent time

trend findings from the State of California (5). " This report was flawed

with methodological errors and weaknesses which were not detected, " he said,

claiming to have detected those errors.

As in his original argument, Fombonne's attack on the California data

is highly flawed and misleading. Compounding the problem, Fombonne

buttresses his argument with two new hypotheses for which he provides no

data and suggests no tests. Both his attack and his new hypotheses are

wrong.

The Attack on the California findings. In his letter, Fombonne cites

two particular concerns with the California data.

* " First, the conclusion that autism has reached epidemic

proportions is based on numbers and not rates. It does not take into account

increasing populations, Fombonne notes. " This statement is literally true,

but irrelevant. California birth data are readily available from government

sources. Rough prevalence rates are readily measurable by dividing the

numbers of persons with autism in each birth cohort by the total number of

births in the same year. This calculation (which I have performed using the

original data) shows an a nearly tenfold increase in the rate of autism

between 1960 and 1995. Fombonne's criticism is little more than a pedantic

quibble.

* " Further, researchers made no attempt to account for changing

diagnostic criteria used over the years...he writes. " The bias reflected in

changing diagnostic criteria is widely cited among skeptics. It is an

untestable assertion. Close examination of changes over the last twenty-five

years reveal only modest difference in criteria since Rutter introduced

categorical methods in 1976. The DSM IV criteria, the criteria set employed

in the birth cohorts with the highest rates in California, were deliberately

designed to be more restrictive than those in DSM III-R. There is

substantial overlap in the reported rates of autism under all diagnostic

methods. This concern, however frequently expressed, is little more than a

smokescreen.

The New Hypotheses. Implicit in his critique of both the California

data and the reported increases are two new hypotheses that Fombonne leaves

unspoken, but his argument, here and elsewhere, depends on them. * The

Hidden Horde Hypothesis: " there is no need to raise false alarms on

putative epidemics nor to practice poor science to draw the attention to the

unmet needs of large numbers of seriously impaired children and adults, "

Fombonne states. Fombonne's assertion that autism prevalence is much higher

than previously thought, requires that there are large numbers of children

that were undiagnosed with autism that are now unrecognized as autistic

today. Depending on which prevalence rate one uses, this would require that

anywhere from 150,000 to 650,000 undiagnosed children with autism (not

including adults, which would triple the number) are at large in the United

States today.

This number dwarfs the only official count of the childhood autistic

population (53,000 receiving services under IDEA in 1999) and raises the

common sense question: where could one possibly locate all these undiagnosed

people with autism? For Fombonne to reject a generation of epidemiological

research, he must be able to prove that these undiagnosed cases exist. There

is no credible evidence to support this claim.

The Miracle Recovery Hypothesis:

Fombonne argues elsewhere (6) that the mere observation of larger

numbers of younger persons with autism does not prove that autism rates are

increasing. He uses the analogy of army enrollment, claiming that if there

is a higher percentage of young people in the Army some might be moved, if

extrapolating blindly, to suggest that " there is a rising epidemic of Army

men in the country " (6). This is an argument, he rightly claims, that

" nobody would dare " to make. True enough.

But he neglects to mention a critical feature of the Army experience:

discharge. The only way that Fombonne's imaginary Army epidemic is avoided

is by young people receiving their discharges from the Army. Similarly, if

children with autism are more prevalent in younger cohorts, the only way to

claim there is no epidemic is if there is a massive " discharge " of suddenly

recovered children from the ranks of the autistic. While parents of autistic

children may devoutly hope this will be the case, there is absolutely no

data suggesting a rate of recovery sufficient to negate the observed levels

of increase. Again, probing Fombonne's underlying hypotheses reveals the

weakness of his position.

Contrary to Fombonne's assertions, the vast body of epidemiological

evidence suggests that 1) autism has increased, 2) the rates of increase

vary by country and 3) the countries with the sharpest levels of increase

have observable environmental differences that may contribute to the

increases.

With minimal scientific backing, Fombonne suggests that we ignore this

body of evidence. He counsels complacency in the face of what is emerging as

the largest childhood public health problem in a generation. His assertions

are dangerously wrong, scientifically unsupported and logically

inconsistent.

There is no room for this (what is essentially a sentimental) bias in

the face of such serious medical problems. Scientists and medical

professionals need to examine the data at hand, test every plausible

hypothesis and get to the bottom of this problem as quickly as humanly

possible. Fombonne's statements are not helpful.

Mark F. Blaxill Cambridge Ma

References: 1. Fombonne E, Du Mazaubrun C, Cans C, Grandjean H, J Am

Acad Child Adolesc Psychiatry 1997 Nov;36(11):1561-9, Autism and associated

medical disorders in a French epidemiological survey.

2. Fombonne E and du Mazaubrun, Soc Psychiatry Psychiatric Epidemiol

1992, 27 (4):203-210. Prevalence of infantile autism in four French regions.

3. Fombonne E, " Epidemiological Surveys of Autism " , in Volkmar ed,

Autism and Pervasive Developmental Disorders, 1998.

4. Fombonne E, Psychol Med 1999 Jul;29(4):769-86. The epidemiology of

autism: a review.

5. California Department of Developmental Services. Changes in the

population of persons with autism and pervasive developmental disorders in

California's Developmental Services System: 1987 through 1998. A Report to

the Legislature, Department of Developmental Services, Sacramento, March

1999. 6. Fombonne E, letter to Dr. Neal A Halsey, June 29, 2000.

>> DO SOMETHING ABOUT AUTISM NOW <<

Subscribe, Read, then Forward the FEAT Daily Newsletter.

To Subscribe go to www.feat.org/FEATnews No Cost!

* * *

On the Short Arm of Chromosome 16

[unless you have a firm grasp of genetics, skip this one. You’ve been

warned.]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_ui

ds=11157797 & dopt=Abstract

1: Hum Mol Genet 2001 Feb 15;10(4):339-352

Sequence, structure and pathology of the fully annotated terminal 2 Mb of

the short arm of human chromosome 16.

s RJ, Peden JF, Lloyd C, Horsley SW, K, Tufarelli C,

Kearney L, Buckle VJ, Doggett NA, Flint J, Higgs DR

MRC Molecular Haematology Unit, Weatherall Institute for Molecular

Medicine, Radcliffe Hospital, Oxford OX3 9DS, UK, The Sanger Centre,

Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK and Los Alamos

National Laboratory, Los Alamos, NM 87545, USA.

We have sequenced 1949 kb from the terminal Giemsa light band of human

chromosome 16p, enabling us to fully annotate the region extending from the

telomeric repeats to the previously published tuberous sclerosis disease

2(TSC2) and polycystic kidney disease 1 (PKD1) genes. This region can be

subdivided into two GC-rich, Alu-rich domains and one GC-rich, Alu-poor

domain. The entire region is extremely gene rich, containing 100 confirmed

genes and 20 predicted genes. Many of the genes encode widely expressed

proteins orchestrating basic cellular processes (e.g. DNA recombination,

repair, transcription, RNA processing, signal transduction, intracellular

signalling and mRNA translation). Others, such as the alpha globin genes

(HBA1 and HBA2), PDIP and BAIAP3, are specialized tissue-restricted genes.

Some of the genes have been previously implicated in the

pathophysiology of important human genetic diseases (e.g. asthma, cataracts

and the ATR-16 syndrome). Others are known disease genes for alpha

thalassaemia, adult polycystic kidney disease and tuberous sclerosis. There

is also linkage evidence for bipolar affective disorder, epilepsy and autism

in this region. Sixty-three chromosomal deletions reported here and

elsewhere allow us to interpret the results of removing progressively larger

numbers of genes from this well defined human telomeric region.

PMID: 11157797

_______________________________________________________

Please help us save a lifetime, your child's and ours'

Send your United Way Contributions to FEAT: Put 16106 on your donor

form at work. Or send to: FEAT PO Box 255722 Sacramento CA 95865

_______________________________________________________

Lenny Schafer, Editor PhD Ron Sleith Kay Stammers

Editor@... Unsubscribe: FEATNews-signoff-request@...