Pervasive developmental disorders in Montreal, Quebec, Canada: prevalence and links with immunizations

Used a statistical trick by using MMR uptake data from one city (Quebec City) and comparing it to autism rates in a different city (Montreal).

Pervasive developmental disorders in Montreal, Quebec, Canada: prevalence and links with immunizations

Eric Fombonne  1 Rita ZakarianAndrew BennettLinyan MengDiane McLean-Heywood

Pediatrics. 2006 Jul;118(1):e139-50. doi: 10.1542/peds.2005-2993.

AAP: A study found that thimerosal and MMR vaccine were not linked to prevalence of pervasive developmental disorders in 28,000 children in Montreal, Quebec, Canada, born between 1987-1998 (including 180 identified with a pervasive developmental disorder). Data ruled out an association between pervasive developmental disorder and either high levels of ethyl mercury exposure or 1- or 2-dose MMR vaccinations.

Abstract

Background: The prevalence of pervasive developmental disorders has increased in recent years. Links with the measles component of the measles-mumps-rubella vaccine and the cumulative exposure to thimerosal through other vaccines have been postulated.

Objectives: The purpose of this work was to estimate the pervasive developmental disorder prevalence in Montreal, Canada, in cohorts born from 1987 to 1998 and evaluate the relationship of trends in pervasive developmental disorder rates with: (1) changes in cumulative exposure to ethylmercury (thimerosal) occurring through modifications in the immunization schedule of young children and (2) trends in measles-mumps-rubella vaccination use rates and the introduction of a 2-measles-mumps-rubella dosing schedule during the study period.

Methods: We surveyed 27749 children born from 1987 to 1998 attending 55 schools from the largest Anglophone school board. Children with pervasive developmental disorders were identified by a special needs team. The cumulative exposure by age 2 years to thimerosal was calculated for 1987-1998 birth cohorts. Ethylmercury exposure ranged from medium (100-125 microg) from 1987 to 1991 to high (200-225 microg) from 1992 to 1995 to nil from 1996 onwards when thimerosal was entirely discontinued. Measles-mumps-rubella coverage for each birth cohort was estimated through surveys of vaccination rates. The immunization schedule included a measles-mumps-rubella single dose at 12 months of age up to 1995, and a second measles-mumps-rubella dose at 18 months of age was added on after 1996.

Results: We found 180 children (82.8% males) with a pervasive developmental disorder diagnosis who attended the surveyed schools, yielding a prevalence for pervasive developmental disorder of 64.9 per 10000. The prevalence for specific pervasive developmental disorder subtypes were, for autistic disorder: 21.6 of 10000; for pervasive developmental disorder not otherwise specified: 32.8 of 10000; and for Asperger syndrome: 10.1 of 10000. A statistically significant linear increase in pervasive developmental disorder prevalence was noted during the study period. The prevalence of pervasive developmental disorder in thimerosal-free birth cohorts was significantly higher than that in thimerosal-exposed cohorts (82.7 of 10000 vs 59.5 of 10000). Using logistic regression models of the prevalence data, we found no significant effect of thimerosal exposure used either as a continuous or a categorical variable. Thus, thimerosal exposure was unrelated to the increasing trend in pervasive developmental disorder prevalence. These results were robust when additional analyses were performed to address possible limitations because of the ecological nature of the data and to evaluate potential effects of misclassification on exposure or diagnosis. Measles-mumps-rubella vaccination coverage averaged 93% during the study interval with a statistically significant decreasing trend from 96.1% in the older birth cohorts (1988-89) to approximately 92.4% in younger birth cohorts (1996-1998). Thus, pervasive developmental disorder rates significantly increased when measles-mumps-rubella vaccination uptake rates significantly decreased. In addition, pervasive developmental disorder prevalence increased at the same rate before and after the introduction in 1996 of the second measles-mumps-rubella dose, suggesting no increased risk of pervasive developmental disorder associated with a 2-measles-mumps-rubella dosing schedule before age 2 years. Results held true when additional analyses were performed to test for the potential effects of misclassification on exposure or diagnostic status. Thus, no relationship was found between pervasive developmental disorder rates and 1- or 2-dose measles-mumps-rubella immunization schedule.

Conclusions: The prevalence of pervasive developmental disorder in Montreal was high, increasing in recent birth cohorts as found in most countries. Factors accounting for the increase include a broadening of diagnostic concepts and criteria, increased awareness and, therefore, better identification of children with pervasive developmental disorders in communities and epidemiologic surveys, and improved access to services. The findings ruled out an association between pervasive developmental disorder and either high levels of ethylmercury exposure comparable with those experienced in the United States in the 1990s or 1- or 2-dose measles-mumps-rubella vaccinations.


14Studies.com

The worst MMR study ever done? We think so. Used a statistical trick by using MMR uptake data from one city (Quebec City) and comparing it to autism rates in a different city (Montreal). No surprise that it was published in Pediatrics. Study author, Fombonne, is one of the most conflicted researchers we have seen.

Actual Question This Study Asked & Answered:

Q: Are MMR uptake and PDD rates related in Montreal?

A: No

Did the study look at unvaccinated children?

A: No

Conflict of Interest:

“In the United Kingdom, Dr Fombonne has provided advice on the epidemiology and clinical aspects of autism to scientists advising parents, to vaccine manufacturers, and to several government committees between 1998 and 2001. Since June 2004, Dr Fombonne has been an expert witness for vaccine manufacturers in US thimerosal litigation.”

Ability to Generalize:

Hard to generalize when you use corrupt data.

Post-Publication Criticism:

High due to poor methodology.

Scoring (Out of 40 possible points):

Asked the Right Question:0

Ability to Generalize: 0

Conflict of Interest: -1

Post-Publication Criticism: -1

Total Score: -2

Guest Critic #1: Dr. David Ayoub

Fombonne’s errors keep vaccine-PDD hypothesis alive in Quebec

By David M. Ayoub, MD

In their article published in the July 2006 issue of PEDIATRICS, Fombonne et al concluded they “clearly failed to detect” an association between either Thimerosal exposure or MMR vaccine uptake and pervasive developmental disorders (PDD) rates in Montreal. (1) We strongly believe their failure to detect such an association was related to methodology and design flaws and that they have not adequately demonstrated that a vaccine link can be dismissed.

Fombonne et al evaluated children enrolled in only one of Montreal’s five school boards in an attempt to estimate the prevalence of PDD in Montreal. The authors appropriately cautioned that PDD rates in Lester B. Pearson School Board (LBPSB) may not have been representative of rates elsewhere and suggested that data from other school boards should be assessed but claimed, “this information was not available in the survey data that we could obtain.”

One of us (MR) easily obtained this data of all five Montreal school boards from the Ministry of Education of Quebec (MEQ). Our analysis indicates that the enrollment at LBPSB in 2003-04 represented only 14% of all total school board enrollments in Montreal. More unusual, the PDD rates at LBPSB were significantly higher than the other four school boards, separately or combined. In some matched birth cohorts the prevalence of PDD was as much as three times higher among LBPSB students. Therefore, Fombonne’s objective to calculate the PDD prevalence in Montreal could not possibly have been accurately estimated by assessment of this particular school board and any conclusions about a relationship between vaccines and PDD rates in Montreal could be seriously flawed.

The authors committed a serious selection bias by choosing to study only a small subset of the children in Montreal’s schools. PDD rates at LBPSB, a Center of Excellence in Autism, are likely influenced by the fact that it is the only totally inclusive school board of the Province and that it has a very high ratio of integration of students with PDD into regular classes. Therefore, many families of children with PDD often seek to enroll their children in LBPSB resulting in an overestimate of true PDD rates in Montreal.

The English-speaking LBPSB is a poor representation of the general Montreal student population whose mother tongue is most commonly French (43%), followed by various non-English languages (37%) and lastly English (22%). (2) Montreal, the second largest French-speaking city in the Western hemisphere, attracts many immigrants. Quebec’s language law Bill 101 which protects the French-language restricts access to immigrants and French-speakers to English schools. Only children of parents having done most of their elementary studies in English can attend English schools. Most French-Canadians and children of immigrants who are a majority in Montreal are forced to attend French schools. Consequently, the LPBSB and other English school boards do not represent Montreal’s true ethnic diversity. In 2004, only 25.9% of Montreal’s student population attended English schools such as LBPSB. (3)

Fombonne et al erroneously stated that Thimerosal-exposure after 1996 was “nil” but analysis of numerous Canadian government healthcare documents suggests otherwise. According to the Public Health Agency of Canada thirty-three licensed vaccines were still in use as of March 2003. (4) Some Thimerosal-containing vaccines, including those against hepatitis B, influenza and meningococcus specifically target infants and early childhood. Since 1994 the majority of 4th grade students participated in an elective Hepatitis B vaccination program, but the first Thimerosal-free hepatitis B vaccine was not licensed in Canada until March 2001, providing more evidence that Fombonne’s study population was exposed to Thimerosal. (5,6) A fully Hepatitis B-vaccinated child could have received 37.5 micrograms of mercury or more by six months of age prior to availability of preservative-free vaccine and within the study period that Fombonne characterized as “nil” mercury exposure. In addition, the reconstituted Penta vaccine available in 1997 still contained 25 micrograms of mercury per dose and could have resulted in an additional 100 micrograms of cumulative mercury exposure in children vaccinated at 2, 4 and 6 and 18 months of age. (7)

Fombonne failed to consider that immunization schedules varied in Montreal resulting in more mercury exposure in some groups than others. According to the Protocole d’Immunisation du Québec foreign-born children and native children less than 7 years old with at least one parent who has emigrated from areas with a high prevalence of Hepatitis B (over 100 countries) must receive the Hepatitis B vaccine series. (8) Meningococcal vaccines, some with Thimerosal, had also been administered more frequently to these groups. More importantly, immigrant children without adequate vaccine records are required to repeat the complete Canadian immunization schedule, further increasing their cumulative exposures. (9)

Regarding internationally adopted children, Sandra Caron, clinical nurse of the International Health Clinic of Ste. Justine’s children Hospital, Montreal wrote: “Practically all children present a vaccinal delay or don’t have the same vaccines than here, or vaccines of foreign countries are more or less reliable, so vaccination has to be readministered from the beginning.”(10) These children therefore represent yet another unique subset of the population that could have been exposed to even larger amounts of Thimerosal during Fombonnes’s “nil” exposure period.

Fombonne et al claim that the vaccine records of the 180 children with PDD were not available, but this seems odd since they claim 80% of the children with PDD had been seen in their own institution. We have obtained several vaccine records from Quebec parents confirming Thimerosal exposure after 1996. For example, the son of one of us (MR), who was adopted from abroad and entered Canada at three months of age, received over 100 micrograms of mercury between October 1997 and March 1998 by the age of six months. It is likely other children in the post-1996 birth cohorts also received Thimerosal.

Because foreign-born children and children of immigrants likely have greater Thimerosal exposures, we performed our own subgroup analysis of PDD at LBPSB in 2003-04 and discovered a rate of 106.6 per 10,000 in foreign-born children vs. 67.6 among natives. PDD rates were also significantly higher among LBPSB children with one or more immigrant parents. Numerous reports of higher PDD rates among immigrants have been reported in Canada and other industrialized countries. A more extensive assessment is clearly warranted.

We must also protest the manner in which Dr. Fombonne evaluated changes in PDD prevalence following adjustments in the cumulative Thimerosal exposure yet applied an entirely different standard when defining cumulative MMR exposure within the same population. A cumulative exposure is typically calculated by multiplying three independent variables: dose per vaccine, shot frequency and coverage rates for each vaccine. Dr Fombonne defined cumulative Thimerosal exposure by considering only the amount in each vaccine and vaccine frequency but ignored coverage rates. He applied the opposite standard to the MMR exposures and only considered coverage rates. Thus, he ignored the fact that autism rates increased following a doubling of the MMR exposure after 1996 when a second MMR shot was added to the immunization schedule and chose to emphasize that a rise in PDD rates coincided with a decline in MMR coverage rates. Obviously the increased amount of administered viral load to the population was far greater influenced by a doubling of shots administered than by a marginal drop in immunization coverage rates. He likewise ignored the potential impact of mass measles immunization campaigns in Quebec that delivered a second dose of measles to a large number of infants and children throughout 1996. (11) The subsequent rise in PDD shortly after that campaign is clearly depicted in their figures and would lead us to believe this observation supports an association between PDD and MMR exposure.

Finally the paper’s observation about rising PDD rates seems to contradict Dr. Fombonne’s well-known contention of the lack of evidence of an autism epidemic. In an Inserm interview, Dr. Fombonne said, “to declare an epidemic, or sensible increase of the prevalence, it would take incidence studies, always the same, year after year, but this data is not available in any country.” (12) The database we obtained from the MEQ represents the type of dataset Fombonne stated was required to detect true increases in PDD. According to one Montreal-based autism organization, data from the MEQ revealed an increase in annual PDD cases in Quebec from 410 (1990-1991) to 4,483 (2005-2006), a nearly 1,000% increase over 15 years. (13) This is staggering and is strong evidence of a real rise in neurodevelopmental illnesses that cannot possibly be solely genetic in nature but supports an environmental etiology.

In conclusion, the numerous flaws in the Fombonne et al study along with the lack of confirmation of non-Thimerosal exposure in their PDD cases renders the paper’s data deceptive and uninterruptible and their conclusions are unsupported.

Guest Critic #2: F. Edward Yazbak, MD, FAAP

A Tale of Two Cities: Flawed Epidemiology

By F. Edward Yazbak, MD, FAAP

In July 2006, Fombonne et al published a report in PEDIATRICS about pervasive developmental disorders, MMR vaccination and Thimerosal. In a letter to the editor of the journal, I reported legitimate concerns about the MMR research and its conclusions. Both Dr. Fombonne and the editor chose to ignore them.

***

On February 2, 2007, I re-submitted a letter to the editor of PEDIATRICS about a study that had been published on July 6, 2006. PEDIATRICS is the journal of the American Academy of Pediatrics (AAP).

I have been a Fellow of the Academy since 1963. This was the first letter to the editor of the journal that I had ever written.

Following is the exact text of my letter:

Far-Fetched

In “Pervasive developmental disorders in Montreal, Quebec, Canada: prevalence and links with immunizations” (1) Fombonne et al reported that in a group of English-speaking Montreal children born from 1987 to 1998, the prevalence of pervasive developmental disorders (PDD) was high and increasing. They also claimed that during the same period, Measles-mumps-rubella (MMR) vaccination coverage had decreased and concluded “Thus, pervasive developmental disorder rates significantly increased when measles-mumps-rubella vaccination uptake rates significantly decreased.”

The MMR uptake data used “were available through N. Bouliane, BN, MSc of the Direction de Santé Publique de la Capitale Nationale” and were “routinely collected in the region of Québec among 5-year-old children attending kindergarten during 1993-2004.”

La Capitale Nationale refers to Quebec City, located 265 kilometers from Montreal. Ms. Bouliane confirmed that the MMR vaccination rates were indeed from the Quebec City area but refused to release them to me because they were administrative internal information only intended for research.

There are several published vaccine uptake surveys of Montreal. MMR vaccination rates of children 24 to 30 month-old in the Montreal area increased from 85.1% in 1983 (Baumgarten) (2) to 88.8% in 1996-97 (Valiquette) (3) to 96% in 2003-04 (Health Department Survey) (4)

The above suggests that in Montreal PDD prevalence and MMR vaccination rates were in fact increasing in tandem during the study period.

The readers deserve to know why the authors compared developmental data from a specific group of children in Montreal with MMR vaccination data from the city of Quebec, some distance away.

References

Conflict of Interest

The author is the grandfather of a child with autistic enterocolitis who has evidence of measles virus genomic RNA in the gut.

***

I received the following response:

20-Feb-2007

Title: Far-Fetched
Manuscript number: 2007-0326

Dear Dr. F. Yazbak:

What follows is a copy of Dr. Fombonne’s e-mail in response to your Letter-to-the-Editor.

“This person is known to pursue the MMR-autism agenda at all costs in order to ‘demonstrate’ a link he strongly believes in. The only way ahead is to encourage him to do independent research. All controlled epidemiological research thus far has concluded to the absence of such a link.”

As a note, I believe the evidence of no link between MMR and Autism is sufficient. It’s not worth publishing more on this subject. We will not be publishing this exchange of correspondence.

Thank you for thinking of Pediatrics.

Sincerely,

Jerold F. Lucey, MD
Editor
Pediatrics Editorial Office

***

The first sentence in Dr. Fombonne’s note is correct. I do believe that a link does exist between MMR vaccination and autism in certain genetically -predisposed children.

The rest of the message is inappropriate both in tone and content and Dr. Fombonne’s statement that “all controlled epidemiological research thus far has concluded to the absence of such a link” is irrelevant and unrelated to my letter.

So is the editor’s personal belief about the “link between MMR and Autism”.

I found and reported a glaring error in the paper. The rates of autism in Montreal have as much to do with MMR vaccination rates in Quebec City as pollution in Los Angeles with Diesel buses in Chicago.

The lead author refused to respond to my criticism concerning that simple geographic fact and the editor was unable to force him to do so.

It is as simple as that.

Furthermore, in order to “estimate the pervasive developmental disorder prevalence in Montreal”, Dr. Fombonne only surveyed children enrolled in one of Montreal ‘s five school boards.

In 2003-2004, that particular English school board only had 14% of all total school boards enrollments in Montreal. In addition, this board was never representative of the true student demographic profile of the city, whose mother tongue is mostly French (43%), followed by various non-English languages (37%) and then English (22%). French and immigrant children who constitute the majority of the school population cannot attend English schools.

My submission to the electronic peer to peer review of PEDIATRICS, also a first, was not published as well.

***

In 2001, Dr. Fombonne reported in PEDIATRICS the results of another study that he had conducted in the United Kingdom. That publication titled “No evidence for a new variant of measles-mumps-rubella-induced autism” (1) was intended to rebuke Andrew Wakefield’s theory. It received little or no attention.

It is not known how many relevant letters to the editor were rejected at the time.

Discussing the 2001 study in their comprehensive Cochrane MMR Review, Demichelli, Jefferson et al reported that “The numbers and possible impact of biases in this study is so high that interpretation of the results is impossible.” (2)

***

When he was in France, Dr. Fombonne was a well known psychiatrist who published articles on psychiatric topics.

He was still a psychiatrist when he moved to England…until Andrew Wakefield suggested that the link between MMR vaccination and autism should be further investigated and suddenly…Dr. Fombonne became a “psychiatrist/epidemiologist” and a consultant to the UK medical authorities on MMR vaccination and autism. He published several articles on the subject including “No evidence for a new variant of measles-mumps-rubella-induced autism” in PEDIATRICS in 2001 (above) but avoided dealing with the Thimerosal issue.

Since his arrival to Montreal, Dr. Fombonne is Chair, Department of Psychiatry and Head of the Division of Child Psychiatry at McGill University. He is also the Director of the Department of Psychiatry at the Montreal Children’s Hospital, yet the lay press often refers to him as an “Epidemiologist”.

Dr. Fombonne was also recognized as an “Epidemiologist” in a Thimerosal-related case in a U.S. Court.

A footnote in the July 2006 publication “Pervasive developmental disorders in Montreal, Quebec, Canada: prevalence and links with immunizations” reads: “In the United Kingdom, Dr Fombonne has provided advice on the epidemiology and clinical aspects of autism to scientists advising parents, to vaccine manufacturers, and to several government committees between 1998 and 2001. Since June 2004, Dr. Fombonne has been an expert witness for vaccine manufacturers in US thimerosal litigation. None of his research has ever been funded by the industry.”

It is obviously customary to disclose sources of funding, Disclosing sources of “Non-Funding” on the other hand is unusual. In any case, it is nice to know that Dr. Fombonne’s research was never funded by the “Industry”.

The statement proves what I mentioned earlier: That Dr. Fombonne only became interested in MMR vaccination in the UK after Andrew Wakefield published his original research on the subject in 1998. It also raises an important question: How did Dr. Fombonne become an “expert witness for vaccine manufacturers” in 2004 when his very first research on Thimerosal was just published in PEDIATRICS on July 6, 2006?

No wonder “Pervasive developmental disorders in Montreal, Quebec, Canada: prevalence and links with immunizations” was so important to “protect” and it is no surprise that Dr. Fombonne chose not to respond to my letter. Besides, what could he have said and how could he have justified the strange fact that he compared developmental information about a specific group of children in Montreal with unrelated MMR vaccination data from Quebec City, a good distance away?

***

Footnote: I am not anti-vaccine nor have I ever been.

References:

1. Fombonne E, Chakrabarti S. No evidence for a new variant of measles-mumps- rubella-induced autism. Pediatrics. 2001 Oct;108(4):E58.
1. Demicheli V, Jefferson T, Rivetti A, Price D. Vaccines for measles, mumps and rubella in children. Cochrane Database Syst Rev. 2005 Oct 19;(4):CD004407. Review

F. Edward Yazbak, MD, FAAP

TL Autism Research
Falmouth, Massachusetts
March 7, 2007


WHAT CRITICS SAID

■ Fombonne et al. evaluated children enrolled in only one of Montreal’s five school boards, Lester B. Pearson School Board (LBPSB), but they cautioned that PDD rates in LBPSB may not have been representative of rates elsewhere and suggested that data from other school boards should be assessed but claimed, “this information was not available in the survey data that we could obtain.”

■ Data from all five Montreal school boards was easily obtainable from the Ministry of Education of Quebec, and they showed that enrollment at LBPSB in 2003-04 represented only 14% of all total school board enrollments in Montreal, but the PDD rates were significantly higher than all four other school boards combined. In some cohorts, prevalence was three times higher in LBPSB than in other districts.[21]

■ Fombonne et al. could not possibly have accurately estimated the citywide rates of PDD merely by assessing just this one school board; any conclusions about a relationship between vaccines and PDD rates in Montreal may be seriously flawed.

■ By choosing to study only a small subset of the children in Montreal’s schools, the authors committed a serious selection bias.

■ LBPSB includes a Center of Excellence in Autism, so its high rates of PDD are likely influenced by the fact that it is the only totally inclusive school board of the Province of Quebec and has a very high ratio of integration of students with PDD into regular classes. Many families of children with PDD often seek to enroll them in LBPSB resulting in an overestimate of true PDD rates in Montreal as a whole.

■ Fombonne et al. chose to study MMR coverage rates, rather than the number of MMR vaccines received. He ignored the fact that autism rates increased following a doubling of the MMR exposure after 1996 when a second MMR shot was added to the schedule and chose to emphasize that a rise in PDD rates coincided with a decline in MMR coverage.

■ Fombonne also ignored the possible effect of mass measles immunization campaigns in Quebec that delivered a second dose of measles to a large number of infants and children throughout 1996.[22] The subsequent rise in PDD shortly after that campaign is clearly depicted in their figures.

■ MMR coverage data was taken from the city of Quebec, rather than from Montreal, where the PDD data was gathered. MMR data “were available through N. Bouliane, of the Direction de Santé Publique de la Capitale Nationale,” the authors wrote. But the “Capitale Nationale” refers to Quebec City, not Montreal, some 265 kilometers away. Ms. Bouliane confirmed that the MMR vaccination rates were from the Quebec City.

■ Published MMR vaccine surveys from Montreal show that rates among children 24 to 30 months old did not fall during the period in question, but actually increased from 85.1% in 1983 (Baumgarten)[23] to 88.8% in 1996-97 (Valiquette)[24] to 96% in 2003-04 (Health Department Survey).[25]

■ This suggests that in Montreal, PDD prevalence and MMR vaccination rates were in fact increasing in tandem during the study period. 

■ F. Edward Yazbak, MD, FAAP, wrote to Pediatrics to protest,[26] and said that “Readers deserve to know why the authors compared developmental data from a specific group of children in Montreal with MMR vaccination data from the city of Quebec, some distance away.”

■ In response, Dr. Fombonne failed to address the criticisms when he wrote to the editor of Pediatrics that, “This person (Yazbak) is known to pursue the MMR-autism agenda at all costs in order to ‘demonstrate’ a link he strongly believes in. All controlled epidemiological research thus far has concluded to the absence of such a link.”[27]

■ The Editor of Pediatrics, Jerold F. Lucey, also wrote to Dr. Yazbak, and stated that “I believe the evidence of no link between MMR and Autism is sufficient.  It’s not worth publishing more on this subject.”

■ Dr. Yazbak subsequently stated: “I found and reported a glaring error in the paper. The rates of autism in Montreal have as much to do with MMR vaccination rates in Quebec City as pollution in Los Angeles with Diesel buses in Chicago. The lead author refused to respond to my criticism concerning that simple geographic fact and the editor was unable to force him to do so.”[28]


SUMMARY:

The criticisms of Fombonne are numerous and cover the most basic questions of study design, data quality, data interpretation and consistency. Furthermore, Fombonne’s ad hominem attacks on his critics undermine his personal credibility. The single most ‘glaring error’ reported by Dr Yazbak, i.e. that “The rates of autism in Montreal have as much to do with MMR vaccination rates in Quebec City as pollution in Los Angeles with Diesel buses in Chicago”, undermines any of the conclusions drawn by the authors. That simple failure to match exposures and outcome is sufficient by itself to render its conclusions worthless.