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 μg) from 1987 to 1991 to high (200–225 μg) 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 ∼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.
Authors without redress?
Surely the authors can find time to respond to my questions - after all do not little children and their parents deserve such clarification?
I realise that recent developments in the UK which suggests that national vaccination databases may be severely flawed - a situation revealed during transfer of records to the new NHS computer system in London - may have embarrassing consequences for those who use UK comparisons to support their numerical results but, having heard no announcements to the contrary, one assumes they remain satsified with the results and conclusions of this study and therefore ought to be comfortable responding to my points of contention?
Conflict of Interest:
Research and Vulnerable Children
I have a number of queries for the authors of this paper.
1. There is evidence that thimerosal was present in vaccines given to Quebec children up to 1997, not only to 1996. Documents such as the Advisory Committee Statement in the Canada Communicable Disease Report Volume 29 of 1st March 2003 evidence that there were various possible thimerosal sources still available for children and adults after 1996 – not least Hepatitis B vaccines given to immigrant children, travel vaccines available for families holidaying abroad, multidose vials of what would otherwise be thimerosal free single vaccines, Flu vaccines given to alleged “at risk” persons including children. The authors fail to demonstrate that ANY of the uncontrolled subject cohorts with or without PDD diagnoses were free of these vaccines, or the additional mercury load such vaccines would induce. During 1997/98 in Quebec there was an outbreak of Hepatitis A in the Jewish community for which medical authorities intervened with HAV shots, some known to carry thimerosal? Were there were no Jewish children registered at the schools during the survey period? About 25% of the Quebec population are immigrants, therefore may have had additional mercury through Hepatitis B shots; a substantial number of children might be statistically expected as suffering from “at risk” conditions whereby flu shots could have been given to children over the age of 6 months. Such additional thimerosal/mercury loading would surely invalidate the authors’ claim to a “thimerosal-free” period from 1996 onwards, thus invalidating the research.
2. The more severe forms of autism can render sufferers incapable of remaining in schools, other than special schools, of which none were included in this study. It is commonly acknowledged that many afflicted children may either be unable to sustain a place in a public school or are eventually excluded, or may not even find a place suitable for placement. Government statistics in the UK shows that over 25% of children with autism have been excluded from schools. Placements at special schools are at a premium, whilst many children home to be educated and cared for when there are no suitable placements. In a cohort of 27,000 children from which only 180 PDDs are identified, were 25% of autistic children already excluded from the schools in question therefore missing from identification through registration, how could a cohort of only 180 remaining identified children provide sufficient statistical power to form meaningful conclusions? Some parents may exclude their children preferring a special school placement for which they may move state, some may be excluded school or vaccination by virtue of religion, some children already believed damaged by vaccines could have been excluded by parental choice and the most severely damaged – if still living and capable of sustaining a school place – maybe of older cohorts - may also have been exempted from further vaccination. These probabilities appear to have been ignored statistically by the authors who have not made an effort to try assess what impact these confounders could have by obtaining information about them, ignorance preferred. Significantly none of the 55 schools are special schools yet all the schools gain handsomely from PDD diagnoses for which funding is at a premium. Would not therefore alternative diagnoses that are borderline PDD, eg ADHD, non-PDD behavioural problems be less preferable to the more heavily funded PDD diagnoses? Could this skew figure or must the authors assume all diagnoses are made without fear or favour? The 55 schools are 45 elementary and 10 secondary, a 4.5:1 bias towards the former and therefore leaves a small cohort of 180 PDDs drawn from a “biased towards elementary” 27,749 children. Therefore a relatively small number of secondary school children for general analysis; a split that is further compromised by the exclusion of 10 secondary school students with a PDD diagnosis who were 17 years old or over as they “could not be related to a meaningful denominator”. The exclusions of about 6 % of the secondary school PDD cohort representing a significant number of 11th Graders, leaves a remainder still represented in the charts and tables.
3. Can the short period of time the study covers (1987 thro’ 1998) for so few children with PDD (180) – or as little as perhaps 6 in one birth year from which to elucidate PDD development – coupled with major alterations and variations in vaccine schedule, diagnostic criteria, major school transitions for ages specified, vaccine types and amounts each child receives for that short period, that makes for an absolutely confusing and confounding set of individual circumstances mean that the statistics employed can never be expected to elucidate accurately? How can the authors expect any rational analysis with such limited cohort sizes, insufficiency of real data thence substituted by guesswork, so many vaccine schedule changes during an 11 year period, major changes to diagnostic policy that threw adjudicators from principles that inevitably identified more autistics than probably existed (DSM-III-R from 1987 to 1994), to ICD-10 from 1992 onwards that conflicted with DSM-III-R and DSM- IV, and DSM-IV from 1994 which inevitably reduced the numbers of autistic persons diagnosed, and introduced Aspergers into the equations – yet the authors make no attempt to evaluate the impact of these issues on total, or small cohorts, per 11 year or single grade period?
4. Does the omission from the study of any form of evaluation of the double dose of MMR after 1996 (only the general rate of uptake of “an MMR vaccine” adorns the study chart and evaluations, whereas it might be more accurate to show a “double uptake” after 1996) affect the study integrity? Clearly various vaccines were in use during the study period. I have already established that thimerosal containing vaccines were (and are still) in use long after the authors claim there were none. How do different makes, batches, ingredients, schedules, doses per child, total adjuvants injected, weight per child, alternative sources of intake of potentially toxic heavy metals aluminium and mercury from environmental, dietary such as sea food, and dental amalgams in older children that would add substantially to the amount and statistical spread of these toxins throughout the authors’ tables and charts? Without any attempt to ascertain exact vaccination analyses for ANY child or group of children from which to be more certain of their published findings the authors appear to be failing in a basic duty of care to children required by ethical bodies where research for children is enacted – by ignoring obvious confounders and making no attempt to quantify the potential power for these omissions to confound results, the lack of specific vaccine status for every subject child, despite there being so few that individual records ought to be available if only for a small subgroup to ascertain typical status instead of assumed, could seriously affect the integrity of the study and impact seriously on all children for whom government policy may be borne out of such impudence.
5. Does the lack of any analysis of those children who, through early vaccination damage, were never registered in such LBPSB schools yet reside in that area affect the integrity of the study? Ignorance of individualised child data means the authors were working purely on relative assumptions, “educated” opinion and guesswork, which surely cannot benefit Quebec children in the main? Age and weight of children vary therefore risk of toxicity to mercury, children who travel abroad, children who suffer coincident “at risk” conditions who receive annual flu shots, children who are immigrants (there was a significant increase in immigrant population to Montreal during the period which is not accounted for, some say as much as 25% influx took place into Montreal) children with dental amalgam mercury loading coincident with mercury-containing vaccination, outflows of children whose parents seek special school placements, children having potentially confused alternative diagnoses (eg ADHD, schizophrenia, bipolar and various behaviour disorders etc.) that are easily confused by the DSM and ICD coding systems, can all bear heavily on analysis – especially where some Grades/years have as little as about 6 PDD children from which to compare “like with like” from other years yet may have been confounded by the addition of doubling of MMR dose, or diagnosis by DSM-IV versus others diagnosed with DSM-III-R or ICD -10. Should only one or two children be “missed” from such a subset the whole paper crumbles like a pack of cards – exclusion of said data does not exclude the probability it exists in sufficient quantity to invalidate any findings. None of this data is difficult to source so the authors must have consciously chosen to avoid that essential realism.
6. Fombonne et al use the fact that some of their other studies arrived at a prevalence rate for all PDDs as about 65/10,000 as some kind of support for their findings herein, yet it was recently revealed in the UK that the figure should be nearer 116/10000 children – so their use of 65/10000 to support their findings is at variance with a reality discovered in recent research at Guys and St Thomas’s, UK, carried out by Professor Gillian Baird et al. Also some of the authors’ reference studies are either discounted or have been severely criticised, for example one of Fombonne’s recent papers was dismissed in a Cochrane MMR Review as “impossible to interpret”. Out of 5000 similar studies the Cochrane team found only 6 studies they felt reasonably valid though still shaky, and many of the references supplied by the authors appear in the 5000.
7. In charts and tables purporting to evidence the MMR and toxic mercury state of those children the authors identify a “linear” increase of around 10% over the period shown; this belies the literally mountainous terrain demonstrated by the figures. The “linear vision” belies obvious hikes and troughs, perhaps expected were thimerosal and MMR vaccines damaging children. It is not difficult to visualise how the dramatic hikes in prevalence from 90-91 and 93-94 might be due to increasing thimerosal loads; and how the dramatic hike from 97-98 might evolve out of prolonged (beyond the authors’ stated end of) thimerosal use in vaccines coupled with doubling of MMR, with perhaps additional mercury from Hepatitis B shots (especially Jewish children and immigrants) and flu shots for the “at risk” creating a very substantial potentially toxic overload of perhaps 300ug ethylmercury along with two MMR jabs, plus standard scheduled vaccines with attendant adjuvants. Not the mythical “free of mercury”, “single dose based MMR uptake graph” for what should represent two MMR shots, topped with the 1994 onwards DSM-IV splitting of a two type PDD coding (DSM-III-R) into a five type PDD coding dramatically reassigning many persons with autism to other eg. Aspergers diagnoses. Without an educated attempt to clarify how much more PDD was identified from 1994 onwards with DSM-IV diagnostics, and how PDD types were reassigned with the advent of Aspergers Syndromes, Retts Syndrome and CDDs, and how the changes are likely to affect the charts one can have no confidence in the charts, results or conclusions.
The “Guidelines for the ethical conduct of medical research involving children” (Arch Dis Child 2000; 82:177-182 by the Royal College of Paediatrics and Child Health: Ethics Advisory Committee) recognises that “children are unique as a research group for many reasons. They are the only people in British law on whose behalf other individuals may consent to medical procedures. Many children are vulnerable, easily bewildered and frightened, and unable to express their needs or defend their interests…. more needs to be known about how children are affected by their experiences as patients and research subjects, and what support they need”. Researchers who indulge in programmes that directly or indirectly impact on certain types and groups of children have a special duty of care to ensure that policies, protocols, methodologies, evaluations, analyses and conclusions are derived through a high level of commitment to comprehensiveness, accuracy and integrity. One may feel that this and other similar studies exclude large tracts of realism such that inappropriate government health, educational and social policy may ensue. Do the authors consider that the most vulnerable children this study purports to represent have a right to expect greatest possible accuracy and objectiveness in determining their current status, and if so, have they made every effort to honour that right?
Conflict of Interest: