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More of that vaccine/autism research that doesn’t exist

17 Jul

There are some parents who want research on vaccines and autism. I may not agree that this is the best way to spend our limited resources, but there’s no denying that this group exists and is very vocal. One thing that surprises me is that these parents appear to be unaware of vaccine/autism research that is ongoing. Not just the studies that come out that show us over and over again that autism risk is not increased by vaccines. But other projects. Biology. Studies on regression. And more. I pointed out recently that using NIH Reporter, one can find a number of projects on autism and vaccines or autism and mercury.

But NIH is not the only Federal agency funding autism research. And there are private funders as well. As I mentioned in my previous article, another place to look for funded research projects is the IACC/OARC Autism Spectrum Disorder Research Portfolio Analysis Web Tool as this includes work the various groups represented on the IACC–both Federal and Private. Unfortunately, this tool only has 2008, 2009 and 2010 projects (had the GAO not required OARC to provide a lot of information last year, perhaps this tool would be updated by now. But such is the government.) But, even with this limitation in years, let’s see what projects come up with searches for vaccines or mercury. I’ll give the titles first, and then the abstracts for these projects below.

It’s understandable that parent advocates are not aware of these projects. I’ve written about this before (“What projects are being funded in autism research? Part 1: vaccines and GI issues”) but I think it’s safe to say that parents who believe in the vaccine/autism connection do not frequent Left Brain/Right Brain. There are places on the web that carry that message (for example, the Age of Autism blog and the sites of the organizations that sponsor it). They aren’t telling their constituencies about the ongoing research efforts. As an example, as I was finishing this article, SafeMinds came out with a letter discussing how no work is being performed on vaccines and autism.

Again, this list is only for 2008, 2009 and 2010. More recent projects from NIH were discussed here.

Vulnerability phenotypes and susceptibility to environmental toxicants: From organism to mechanism (funded by Autism Speaks)

Evaluation of the immune and physiologic response in children with autism following immune challenge (funded by Autism Speaks)

Vaccination with regression study (funded by Autism Speaks)

Vaccine safety datalink thimerosol and autism study (Federally Funded)

Analysis of developmental interactions between reelin haploinsufficiency, male sex, and mercury exposure (Funded by Autism Speaks)

MeHG stimulates antiapoptotic signaling in stem cells (Federally funded: DoD)

Etiology of autism risk involving MET gene and the environment (Funded by Autism Speaks)

Epidemiological research on autism in Jamaica (Federally Funded, NIH)

investigation on the potential harmful effects of mercury in the nonhuman primate (Funded by SafeMinds)

Investigating the effect of mercury on ASD, AD and ASD regression (Funded by SafeMinds)

The effect of mercury and neuropeptide triggers on human mast cell release of neurotoxic molecules (Funded by SafeMinds)

Does mercury and neurotension induce mitochondrial DNA release from human mast cells and contribute to auto-immunity in ASD? (Funded by SafeMinds)

Toxicant-induced autism and mitochondrial modulation of nuclear gene expression (Federally Funded: DoD)

Below are the abstracts for these research projects.

Vulnerability phenotypes and susceptibility to environmental toxicants: From organism to mechanism (funded by Autism Speaks)

One hypothesis regarding the association between genetic changes, environmental factors and autism is that many mutations or polymorphisms make the organism more vulnerable to later exposure in some individuals. Called the “vulnerability phenotype”, the Noble lab hypothesizes that one potential unifying theme of the vulnerability phenotype of children with ASD is that they are more oxidized. This elevated oxidation state has been shown to be sufficient to cause dramatic changes in cellular function. In this project, Dr. Noble will test the hypotheses that genetically-based differences in oxidative status are associated with differences in vulnerability to physiological stressors in vitro and in vivo, with even greater increases in vulnerability to combinations of physiological stressors. Specifically, thimerosal and other vaccine adjuvants will be studied. The second part of the study will determine if these effects on a novel regulatory pathway called redox/Fyn/c-Cbl is a necessary mechanistic convergence for increases in vulnerability caused by a more oxidized metabolic status. These results will provide a better understanding of the biochemical effects and mechanisms of possible toxicity of vaccines and vaccine additives. What this means for people with autism: These studies will initially focus on the combination of vaccine additives, but then examine whether a background genetic vulnerability phenotype affects the response to these additives. The results would provide new targets for intervention against the adverse effects of increased oxidative status in children with autism.


Evaluation of the immune and physiologic response in children with autism following immune challenge
(funded by Autism Speaks)

The overall goal of this proposal is to address immune function in children with autism, including the response to vaccine challenge, and how that relates to behavior. Evidence suggests that autism is associated in some cases with altered immune function, but the response of the immune system in children with autism to specific immune challenges, such as vaccines, has not been investigated directly. While it has been reported that some children with autism respond poorly following vaccination with symptoms ranging from rash, diarrhea, irritability, seizures, and loss of skills, no careful, thorough approach has been undertaken to fully characterize this issue, both at the biology and behavior level. We propose to use our current CHARGE (Childhood Autism Risks from Genetics and the Environment) and Autism Phenome Project (APP) study population to address this critical issue. The overall approach would include an examination of the immune response to both viral and bacterial vaccines in children with autism, as compared to typically developing age-matched controls, in real time following vaccination at 5 years of age. Vaccines have advantages for directly studying the immune response as they provide a known, scheduled immune challenge, whose dose is well characterized – making it possible to collect and interpret immune response data at the time that it occurs. Therefore, we think that exposure to an immune challenge with vaccine would result in an increase in inflammation compared to controls in a subpopulation of children with autism. However, we also anticipate that some children will respond to vaccine challenge differently, depending on form of the vaccine, i.e. viral vs. bacterial. Thus, we propose to address the issue of immune function in children with autism through a careful analysis of the immune system, medical and mitochondrial issues, and behavioral response to both viral and bacterial vaccines.

Vaccination with regression study (funded by Autism Speaks)

A major challenge to studying autism with a suspected vaccine-related regression is identifying children with acute regressive-type symptoms following MMR vaccination; there are no specific codes, tests, or procedures that identify this occurrence with a high degree of specificity. This study will explore the Kaiser Permanente electronic databases to ascertain whether we can identify children with regressive type autism and identify the timing of the regression in relation to the period directly following MMR vaccination. In order to see if identification of regressive autism from medical records is possible, the investigators will attempt to identify children vaccinated with MMR who then abruptly undergo a ‘cluster’ of visits, tests, and/or procedures in the time period directly following vaccination. The researchers feel that there may be a number of children who receive a diagnosis (such as ‘prolonged crying’) in the emergency department on the day after vaccination, followed shortly thereafter (1-2 days later) by another set of diagnoses (such as ‘fever’ & ‘irritability’) in the pediatric office or other outpatient department, and then receive either diagnostic or laboratory tests indicating (at least) a moderate degree of severity of concern, such as CT scans, metabolic testing, or referral to neurology. If this study is successful in using medical databases to identify a specific group of children with demonstrable autism-related regression that clearly follows vaccination, it may point to the feasibility of further studies concentrating on this specific population.

Vaccine safety datalink thimerosol and autism study (Federally Funded)

The Thimerosal and Autism Study is a case-control study conducted in three U.S. managed care organizations (MCOs). Data collection began in 2005 and took three years to complete. In this study, children who were diagnosed with autism were matched with control children. The autism diagnosis of the case samples was confirmed by a standardized clinical assessment protocol. Vaccination histories and information on other potential confounding factors were confirmed by reviewing the medical records for all children. In addition, the mothers of both cases and matched controls were interviewed.

Analysis of developmental interactions between reelin haploinsufficiency, male sex, and mercury exposure (Funded by Autism Speaks)

This project will investigate the role of three separate factors in an animal model of autism spectrum disorder: a) genetic susceptibility, b) hormonal environment, and c) possible environmental triggers. A mouse model with a mutation of the reelin gene, implicated in autism spectrum disorders, will be studied after exposure to methyl and ethyl mercury. Both behaviors and neuropathological endpoints will be explored. Finally, the role of endogenous sex hormones will be examined by eliminating the testosterone “surge” around the time of puberty. The individual effects of each will be examined, as well as the interaction of the three components (genetic liability, environmental exposure, hormonal influences) to determine gene x environment interactions. What this means for people with autism: This study will use a unique design to study multiple factors in the etiology of autism spectrum disorder in a mouse model, isolating and combining factors which previously have been implicated in the pathophysiology and behavioral phenotype.

MeHG stimulates antiapoptotic signaling in stem cells (Federally funded: DoD)

This project is a study of the antiapoptotic effect of low concentration of methly mercury and cadmium in cells.

Etiology of autism risk involving MET gene and the environment (Funded by Autism Speaks)

Two independent lines of evidence indicate that the maternal immune system and a functional genetic variant contribute to autism spectrum disorder (ASD) risk. Here, the Van De Water lab will partner with scientists at Vanderbilt University to examine whether these two seemingly unrelated contributions may converge to define a unique ASD susceptibility. Preliminary evidence collected by the Van De Water lab indicates an association between the Mesenchymal epithelial transition factor (MET) gene ‘C’ type, which reduces MET protein expression, and the presence of specific maternal anti-fetal brain autoantibodies. This relationship suggests that this as a pathway for production of the maternal autoantibodies, leading to a gene x environment interaction underlying ASD susceptibility. The next line of experiments will examine the relationship in an even larger sample and assess the functional effect of the MET gene polymorphism on immune cell activity as well as further examine the impact of environmental toxins (including ethyl mercury) on the gene expression-dependent function of maternal immune cells.

Epidemiological research on autism in Jamaica (Federally Funded, NIH)

The prevalence of autism spectrum disorders (ASD) appears to be on the rise in developed countries and has become a serious public health concern. In most developing countries, however, the nature and prevalence of factors associated with ASDs are unknown. The long term goal of this planning project is to develop capacity for conducting large scale population-based ASD studies in Jamaica. First, the diagnostic criteria used in Jamaica and the United States will be compared. Then, questionnaires regarding the demographic and socioeconomic position, occupation, and drinking habits of each child’s parents will be used, and information will be gathered about family history of developmental disorders, family size, birth order of the affected child, and whether the child is taking any medications. An age and sex matched case-control study, including a dietary questionnaire, will also be conducted to investigate whether environmental exposures to mercury, lead, arsenic, and cadmium play a role in autism. Blood and saliva samples will be collected to determine if any DNA polymorphisms that might affect interactions with heavy metals are present in children with ASD. New knowledge of potential environmental risk factors for ASD may arise from this research, thereby reducing physical, psychological, and economic burdens on the child, family, and society and helping parents make decisions about avoiding exposure to environmental contaminants.

An investigation on the potential harmful effects of mercury in the nonhuman primate (Funded by SafeMinds)

An investigation into the effect of mercury on neurons, astrocytes, and microglia on the central nervous system of the nonhuman primate.

Investigating the effect of mercury on ASD, AD and ASD regression (Funded by SafeMinds)

An investigation into the influences of demographics and environmental variables in the development of neurodevelopmental problems such as AD, ASD, and ASD-regression

The effect of mercury and neuropeptide triggers on human mast cell release of neurotoxic molecules (Funded by SafeMinds)

An investigation to determine the pro-inflammatory effects of mitochondrial DNA with and without mast cell triggers.

Does mercury and neurotension induce mitochondrial DNA release from human mast cells and contribute to auto-immunity in ASD? (Funded by SafeMinds)

Further investigation into preliminary data that neurotensin (NT) stimulates mast cell activation and that NT is elevated in young children with autism spectrum disorder.

Toxicant-induced autism and mitochondrial modulation of nuclear gene expression (Federally Funded: DoD)

Autism has been associated with epigenetic changes: Tiny chemical tags in the regulatory regions of genes that affect how genes express themselves by turning them on or off. One gene often decreased in expression in the brain tissue of autistic individuals is MECP2, a gene that governs the expression of genes crucial to brain development. Exposure to environmental pollutants is also thought to play a role in autism. These two phenomena both involve a small cellular organ called mitochondria. The suspect environmental pollutants are toxic to mitochondria, which play a critical role in epigenetics: Pollution exposure can lower the amount of mitochondrial DNA (mtDNA) in a cell, causing an increase in placement of epigenetic tags by DNMT1 that leads to gene silencing. We hypothesize that exposure during pregnancy to pollutants toxic to mitochondria causes a decrease in mtDNA copy number and increased placement of epigenetic tags by DNMT1 on key developmental genes, affecting pathways that have direct roles in the development of autism. We will expose mice, during pregnancy, to selected toxicants and evaluate adult behavior and associated biochemical changes in brain tissue. Valproic acid will be used as a positive control, with saline as a negative control. The environmental pollutants lead, arsenic, cadmium, manganese, mercury, and permethrin will be investigated for their potential to induce autistic behavior changes. Brain tissue will then be used for molecular studies of mtDNA copy number, expression of DNMT1, and alterations to the epigenome on both a genomewide and gene-specific level.


By Matt Carey

Note: I serve as a public member to the IACC. My views here and elsewhere are my own, not those of the Committee.

Why won’t the government fund vaccine/autism research?

15 Jul

This question gets brought up a lot by some parent advocates. The are informed by groups promoting the idea of vaccine causation that the government is blocking this work. The evidence points strongly away from vaccines as a primary cause of autism, and investment in this area doesn’t seem wise. At least that’s the viewpoint of the majority of parents (including myself), autistics and researchers. But some remain unconvinced and want vaccine/autism research performed. And they are upset that none of this work is being performed.

Here’s a different question: why are the groups who promote the idea that vaccines cause autism failing to inform their members that, yes, indeed vaccine/autism research is being performed?

Or, to put it simply: vaccine/autism research is being performed and it’s being funded by the government. But you wouldn’t know that if you read, say, the Age of Autism blog, Generation Rescue’s website, SafeMinds’ website, or the other groups advocating for this research. If you are interested in vaccine/autism research and you are reading about these projects for the first time here, ask yourself “why have these orgs not informed me of this?”.

As noted here recently, Tom Insel discussed an upcoming vaccine/autism study. Already commissioned, performed and in the publication stage. That announcement was in April. What was the response from the community that has pleaded for vaccine/autism research? For the first few months: Silence. In July, SafeMinds finally put out an article showing that they were “worried” about this study. I don’t see much discussion of this announcement from other groups or outlets.

I’m not surprised by this. I’ve noted before that work on areas such as vaccines, mercury, environmental risk factor research and GI dysfunction don’t get discussed by the groups that are focused on these topics. I’ve covered the research in these areas more than they have.

So let’s get back to what other work is going on in vaccines and autism. Let’s start with the simple question: how would you find out? One place is the IACC/OARC Autism Spectrum Disorder Research Portfolio Analysis Web Tool. That could use updating, but it is an easily searchable database. Another place is NIH Reporter. It’s less easy to use than the Portfolio Analysis Tool and includes all of NIH. I.e. it covers non autism topics and doesn’t include projects being done outside of NIH (say, by Autism Speaks or other private funders). But, search Reporter for autism and vaccines or mercury and what do you get? Quite a number hits. Let’s consider a few.

How about:

There’s a study by Ian Lipkin’s group at Columbia titled: GENE-ENVIRONMENT INTERACTIONS IN AN AUTISM BIRTH COHORT.

There’s a study by Gene Sackett’s group, A PRIMATE MODEL OF GUT, IMMUNE, AND CNS RESPONSE TO CHILDHOOD VACCINES. This appears to be a follow on project to the Laura Hewitson studies that were discussed a great deal online a few years ago.

Isaac Pessah’s group at the UC Davis MIND Institute has a project NEURODEVELOPMENTAL TOXICOLOGY OF AUTISM. Prof. Pessah also had a multiyear project ENVIROMENTAL FACTORS IN THE ETIOLOGY OF AUTISM

Judy Van de Water’s group at UC Davis MIND Institute has a project IMMUNOLOGICAL SUSCEPTIBILITY OF AUTISM.

The Lewin Group study (which I believe is the one mentioned by Tom Insel) STUDY OF HEALTH OUTCOMES IN CHILDREN WITH AUTISM AND THEIR FAMILIES. (Just a note–see how this has been publicly available information for a year?)

There’s the CHARGE study, which is looking at a large array of potential environmental risk factors, including specifically mentioning mercury. THE CHARGE STUDY: CHILDHOOD AUTISM RISKS FROM GENETICS AND THE ENVIRONMENT

Here’s a 2014 grant to Ray Palmer, well known to the groups promoting mercury as a cause of autism, PRENATAL TIMING OF HEAVY METAL EXPOSURES FROM AUTISTIC AND NON-AUTISTIC CHILDREN.

The EPIDEMIOLOGICAL RESEARCH ON AUTISM IN JAMAICA – PHASE II project is continuing (hence the Phase II) and includes work on mercury.

There are more projects. Some I left out because they are older. But I think the point is made and is very clear: vaccine/autism and mercury/autism research are being funded.

And that is without even discussing how research on the biology of autism feeds into all etiological questions. Whether it’s vaccine, genetics or what have you, if you understand the biology, you have a better chance of understanding the cause. (when I searched NIH Reporter with the terms Autism and Immune, I got 25 pages of hits. Sure, not all are on-topic, but that’s 25 pages, 606 topics).

Here are the full abstracts–with emphasis added by me–for the NIH Reporter projects mentioned above.

GENE-ENVIRONMENT INTERACTIONS IN AN AUTISM BIRTH COHORT.

Abstract Text:
Reports of increasing prevalence of autism spectrum disorders (ASDs), a set of highly genetic conditions, are intensifying interest in the role of environmental exposures, including infectious, immune, and toxic factors. Retrospective studies exploring associations between environmental factors and ASDs are compromised by selection bias, small sample sizes, possibly invalid diagnosis, and absence of biologic measures. This prospective study will employ an unselected birth cohort of 75,500 in which cases are ascertained through screening of the entire population, diagnoses established using uniform procedures, extensive histories and clinical data obtained, and biologic samples collected serially throughout pregnancy and early childhood. The application of high throughput laboratory assays to derive maximal information from developmentally-influenced, finite, and nonrenewable biologic samples, and inclusion of early screening and diagnostic assessments, will permit an unprecedented, rich view of the longitudinal trajectory and nascent signs and symptoms of ASDs, facilitate discovery of biomarkers, and afford unique insights into the role of gene:environment interactions in ASD pathogenesis. Specific aims are to: (1) establish the autism Birth Cohort (ABC) through ascertainment of cases of autism spectrum disorder (ASD, N=150-233) and selection of controls (N-1000) from the Norway Mothers and Child (MoBa) cohort; (2) examine biologic pathways that may predispose to ASD, through evaluation of immune, endocrine, and neuroregulatory factors in mothers during early gestation or at birth and in children, at birth or 30 months postnatal; (3) identify environmental factors that may be directly or indirectly associated with ASD, including pre- or postnatal infection, vaccination, very low birth weight or other obstetric risk factors in which infections are implicated, dietary and/or environmental exposure to methylmercury; (4) describe the natural history of clinical, anthropometric, and neurobehavioral features of ASD; and (5) explore genotypic influences that may be directly or indirectly associated with ASD by testing associations of ASD and/or its endophenotypes with family history of autoimmune disease or selected candidate genes, and investigating conditional gene-environment effects using antecedent factors found to influence ASD risk.

NIH Spending Category:
autism; Brain Disorders; Clinical Research; Genetics; Immunization; Mental Health; Mental Retardation (Intellectual and Developmental Disabilities (IDD)); Neurosciences; Pediatric; Prevention; vaccine Related

Project Terms:
autism spectrum disorder; Autistic Disorder; Autoimmune Diseases; base; Biological Assay; Biological Markers; Birth; Candidate Disease Gene; case control; Child; Clinical; Clinical Data; cohort; Cohort Studies; Collaborations; Collection; Confusion; Control Groups; design; Development; Diagnosis; Diagnostic; Discipline of obstetrics; Disease; disorder risk; Drops; early childhood; Endocrine; endophenotype; Environment; Environmental Exposure; Environmental Risk Factor; Epidemic; Epidemiologic Studies; Evaluation; Exposure to; Family history of; gene environment interaction; Genes; Genetic; Hereditary Disease; Immune; immune function; Infection; insight; interest; Investigation; Laboratories; Life; Measles; Measures; member; Mercury; Methylmercury Compounds; Mothers; Mumps; Natural History; Nested Case-Control Study; neurobehavioral; Neurodevelopmental Disorder; Norway; novel; Pathogenesis; Pathway interactions; Phase; Population; postnatal; Pregnancy; prenatal; Prevalence; Procedures; prospective; Prospective Studies; Recording of previous events; Relative (related person); Reporting; Research; Research Design; Retrospective Studies; Risk Factors; Role; Rubella; Sample Size; Sampling; Screening procedure; Selection Bias; Signs and Symptoms; Specimen; Testing; Vaccination; Vaccines; Vacuum; Very Low Birth Weight Infant

A PRIMATE MODEL OF GUT, IMMUNE, AND CNS RESPONSE TO CHILDHOOD VACCINES.

Abstract Text:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject’s principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Diagnoses of childhood developmental disorders involving autism-spectrum symptoms are increasing, estimated to affect 1 in 100 children in the United States. Childhood Vaccines have been hypothesized to be contributory factors to this increase. The childhood vaccine regimen has an experimentally unstudied potential for cumulative and synergistic toxicities and possible immunologic interference to normal development. A prior study developed a primate model to assess neurodevelopmental consequences of the 1994-1999 pediatric thimerosal vaccine regimen (1994-1999). Significant neurodevelopmental deficits were evident for vaccinated animals in survival reflexes and standardized cognitive tests, and exposed animals developed gastrointestinal inflammation associated with focal transmural colitis, lymphoid hyperplasia, and syncytia.

NIH Spending Category:
autism; Brain Disorders; Cancer; Digestive Diseases; Immunization; Lymphoma; Mental Health; Mental Retardation (Intellectual and Developmental Disabilities (IDD)); Pediatric; Rare Diseases; vaccine Related

Project Terms:
Affect; Animals; Autistic Disorder; Child; Childhood; Cognitive; Colitis; cost; Development; developmental disease/disorder; Diagnosis; Funding; gastrointestinal; Giant Cells; Grant; Immune; Immunologics; Inflammation; lymphoid hyperplasia; Modeling; National Center for Research Resources; Neurodevelopmental Deficit; Primates; Principal Investigator; Reflex action; Regimen; Research; Research Infrastructure; Resources; response; Source; Symptoms; Testing; Thimerosal; Toxic effect; United States; United States National Institutes of Health; Vaccinated; Vaccines

NEURODEVELOPMENTAL TOXICOLOGY OF AUTISM

Abstract Text:
The long range goal is to determine if exposure to environmental toxicants early in development contributes to the etiology of neurodevelopmental disorders such as autism. A related goal is to determine whether susceptibility to autoimmune disease increases the neurotoxicity of environmental contaminants and increases the risk for developing disorders such as autism. Understanding how exposure to environmental toxicants may contribute to the etiology of neurodevelopmental disorders is important so that the exposure risks can be identified and minimized. If immune system dysfunction is found to increase the risk of exposure to environmental toxicants, then exposure limits to toxic substances can be lowered, and children with immune system dysfunction who may be at increase risk can be identified and protected. The specific aims are to expose mouse strains with low (C57BL/6J) or high (SJL mice) susceptibility to autoimmunity perinatally to either methylmercury (MeHg), polychlorinated biphenyl 95 (PCB 95) or polybrominated diphenyl ether 47 (BDE 47). We will then compare the effects of toxicant exposure between these mouse strains on brain development, complex social behaviors, and immune system function. The hypothesis is that perinatal exposure to each of these toxic substances will impair brain development and behavior, and that suscepbility to autoimmune disease will increase the neuro- and immunotoxicity of these agents. We will also explore a potentially new model of autism in mice injected prenatally with unique autoantibodies isolated from the serum of mothers who have given birth to two more more autistic children. Brain development will be examined histologically using stereological procedures and immunohistochemistry. Complex social behaviors will be studied using behavioral testing procedures established in our laboratory that measure social recognition, social interaction and social communication in mice. Immune system status will be established by measuring cytokines, chemokines, immunoglobulins, and quantifying immune system response to antigenic stimulation. In addition, seizure susceptibility will be measured in toxicant-exposed mice as well as measures of synaptic excitibility and plasticity in hippocampal brain slices. These studies will provide critical new information on the role of the immune system and its interaction with environmental contaminants in autism and other neurodevelopmental disorders.

NIH Spending Category:
autism; Autoimmune Disease; Behavioral and Social Science; Brain Disorders; Epilepsy; Mental Health; Mental Retardation (Intellectual and Developmental Disabilities (IDD)); Neurodegenerative; Neurosciences; Pediatric; Perinatal Period – Conditions Originating in Perinatal Period

Project Terms:
Age; Animal Testing; Antibodies; Anxiety; autistic Children; Autistic Disorder; Autoantibodies; Autoimmune Diseases; Autoimmune Process; Autoimmunity; Behavior; behavior test; Behavioral; Biological Assay; Birth; Brain; CCL2 gene; CCL3 gene; CCL4 gene; Cerebellum; chemokine; Chemokine (C-C Motif) Ligand 4; Child; Complex; cytokine; density; Development; developmental disease/disorder; developmental neurotoxicity; Disease; Environmental Pollution; Enzyme-Linked Immunosorbent Assay; Etiology; Exposure to; fetal; Fibroblast Growth Factor; Flurothyl; Fright; Glutamate Receptor; Goals; Granulocyte-Macrophage Colony-Stimulating Factor; Hippocampus (Brain); Histologic; Homer 1; human TNF protein; IL8 gene; Immune response; Immune system; Immune System and Related Disorders; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Immunohistochemistry; Immunophilins; immunotoxicity; In Vitro; in vivo; Infection; Interferon Type II; Interleukin-10; Interleukin-17; Interleukin-4; Interleukin-5; Interleukin-6; Kindling (Neurology); Laboratories; Learning; Leptin; link protein; Long-Term Potentiation; Measures; Memory; Metabotropic Glutamate Receptors; Methods; Methylmercury Compounds; Mitogens; Modeling; Mothers; mouse model; Mouse Strains; Mus; N-Methylaspartate; neurobehavioral disorder; neurodevelopment; Neurodevelopmental Disorder; Neurologic; Neuronal Injury; Neurons; neurotoxicity; offspring; Pentylenetetrazole; Perinatal; Perinatal Exposure; phenyl ether; Plasma; Poisons; Polychlorinated Biphenyls; postnatal; Predisposition; pregnant; prenatal; prenatal exposure; Preparation; Principal Investigator; Procedures; programs; Proteins; RANTES; receptor; receptor function; repaired; Research Design; Research Personnel; research study; response; Risk; Role; Ryanodine Receptor Calcium Release Channel; Ryanodine Receptors; Seizures; sensory gating; Sensory Motor Performances; Serological; Serum; Signal Pathway; Signal Transduction; SJL Mouse; SJL/J Mouse; Slice; Small Inducible Cytokine A3; social; Social Behavior; social communication; Social Interaction; Source; Splenocyte; Structure; Synapses; synaptotagmin; System; T-Cell Proliferation; Testing; Tetanus; Tetanus Toxoid; Tetanus vaccine; Toxic Environmental Substances; toxicant; Toxicant exposure; Toxicology; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factors; Western Blotting; Work; Xenobiotics

IMMUNOLOGICAL SUSCEPTIBILITY OF AUTISM.
Abstract Text:
Recent studies indicate that immune function in children with autism spectrum disorder (ASD) is profoundly altered compared to developmentally healthy controls. There is a strong interface between the immune system and the neurologic network, and successful neurodevelopment is contingent upon a successful interaction between these two systems. We have identified several aspects of immune dysfunction in patients with autism compared with typically developing controls. These include a reduced response to vaccine antigens of bacterial origin, altered cytokine levels in plasma and upon stimulation of PBMC, increased levels of leptin in patients with early onset autism, and autoantibodies to brain antigens. This wide and complex variety of immune anomalies noted in our first funding period is in keeping with the broad range of phenotypes encompassed by the autism spectrum. Thus, we will build upon our earlier findings of both serologic and cellular changes in immune function. While our studies in the previous project period were aimed at a broad analysis of immune function in patients with autism, the current proposal will address the mechanisms responsible for the numerous alterations in immune homeostasis uncovered in our earlier studies. Therefore, our primary focus will be on the mechanisms responsible for such anomalies in immune function through an in depth analysis of cellular immune function. Our overall hypothesis is that patients with autism have a fundamental defect at the cellular level that ultimately leads to abnormalities in immune function and heightened susceptibility to environmental triggers. To examine this, we propose to: (1) examine longitudinally the serologic profile of children with ASD to ascertain whether the various immune changes noted in our first studies are maintained and/or deteriorating further; (2) determine which immune cell population(s) plays a critical role in the immune dysfunction seen in patients with autism; and (3) fully characterize the autoantibody response in a subpopulation of children with ASD and some mothers of children with ASD. It must be noted that due to the highly heterogeneous nature of autism, there will potentially be immunologic differences that relate to sub-groups of patients with autism. Therefore, we will carefully define the study groups based on our current data to include children with early onset autism, children with delayed onset/regressive autism, general population controls, and children with developmental disorders without ASD. The studies will be performed on CHARGE subjects formerly analyzed by our laboratory (CHARGE-BACK study). This will allow us to extend our prior studies longitudinally to determine if the immune dysregulation, such as increased leptin levels in the early onset patients, remains over time. The following aims address both the serologic and cellular aspects of immune function in patients with autism.

NIH Spending Category:
autism; Brain Disorders; Mental Health; Mental Retardation (Intellectual and Developmental Disabilities (IDD)); Neurosciences; Pediatric

Project Terms:
Address; Age; anti-IgM; Antibodies; Antigens; autism spectrum disorder; autistic Children; Autistic Disorder; Autoantibodies; B-Lymphocytes; Back; base; Behavior; Blood Cells; Brain; calcium indicator; Calcium Signaling; Cell Culture Techniques; Cell physiology; Cell Proliferation; Cell surface; Cells; Child; Color; Complex; Cultured Cells; cytokine; Data; Defect; Development; developmental disease/disorder; Digestion; Disease; Dose; Dyes; early onset; Environmental Health; Etiology; fetal; Flow Cytometry; Flu virus; Frequencies (time pattern); Funding; Gel; General Population; HLA-DR Antigens; Homeostasis; Human; IgE; Immune; immune function; Immune system; Immune System Diseases; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunologics; Label; Laboratories; Lasers; Leptin; Maps; Mercury; Microarray Analysis; Mitogens; Modeling; Mothers; Mus; Nature; neurodevelopment; Neurologic; Oligonucleotides; Pathogenesis; Pathology; Patients; Pattern; Peptides; Peripheral Blood Mononuclear Cell; Phenotype; Plasma; Play; Poly I-C; Population; Population Control; Predisposition; Pregnancy; Principal Investigator; Production; programs; Reagent; research study; response; RNA; Role; Serological; Serum; Source; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Staining method; Stains; System; T-Lymphocyte; Testing; Time; TNFSF5 gene; Tube; Up-Regulation (Physiology); Upper arm; vaccine Antigen; Xenobiotics

STUDY OF HEALTH OUTCOMES IN CHILDREN WITH AUTISM AND THEIR FAMILIES

Abstract Text:
This contract modification is to extend and supplement Contract HHSN271201000033C, consistent with the scope of work of “Study of Health Outcomes in Children with autism and Their Families¿ in order to access the currently validated database developed under the contract to provide for further analysis . Autism Spectrum Disorder (ASD) is a significant public health concern, with an estimated prevalence of 1 in 88 children in the United States. Much of the research to date has focused on the core social and communication deficits of ASD, but there are anecdotes and some survey data suggesting that the rate of comorbid health conditions may also be elevated in this population. Furthermore, despite several large-scale epidemiological studies that have assessed but not found any potential association between ASD and vaccinations, public concerns persist about such a causal link. At least partly as a consequence, health officials in the United States have reported an increased rate of vaccine refusal in the general population. The Study of Health Outcomes in Children with autism and their Families was begun two years ago. Under this contract, the Contractor analyzed a large dataset of retrospective commercial health plan claims of 46,236 children with ASD, their parents and siblings, and a comparison cohort of children and family members. They successfully completed the analyses requested in the original statement of work, which included a study of the validity of ASD diagnoses in the claims data, and descriptions of health outcomes and health care utilization of the ASD cohort, their family members, and the comparison cohorts.

NIH Spending Category:
autism; Brain Disorders; Immunization; Intellectual and Developmental Disabilities (IDD); Mental Health; Pediatric; Prevention; vaccine Related

Project Terms:
Anecdotes; autism spectrum disorder; Autistic Disorder; Child; cohort; Contractor; Contracts; Data; Data Set; Databases; Diagnosis; Epidemiologic Studies; Family; Family member; General Population; Health; health care service utilization; Health Planning; Link; Modification; Outcome; Parents; Population; Prevalence; public health medicine (field); Recording of previous events; Reporting; Research; Siblings; social communication; Surveys; United States; Vaccination; Vaccines; Work

CORE D: MOLECULAR GENOMICS CORE

Core 4 is the Molecular Core. It serves as the central resource for the projects that isolate and process RNA on Affymetrix microarrays, and for performing RT-PCR confirmation of the microarray data for those projects. The UCD Affymetrix Core Facility is run by Dr. Jeffrey Gregg and is equipped with fluidics stations, hybridization ovens, and the new scanner required to scan the human Affymetrix U133 2.0PLUS arrays. Preliminary data from the previous CHARGE study has shown that there are changes in gene expression in the blood of children with autism compared to control children in the general population (GP) and to control children with mental retardation and developmental delay (MR/DD). The blood genomic profile in children with autism without regression (A) was different from controls, autism spectrum disorder (ASD) and different from children with autism with regression (A-R). In addition, there is a group of regulated genes in most children with A, A-R and with ASD that are expressed by natural killer (NK) cells in peripheral blood, suggesting an abnormality in this cell type that is common to all types of autism. These NK-cell related genes are expressed by all of the autism phenotypes including A, A-R and ASD, and hence may point to common pathways that underlie the common language and behavioral abnormalities in all three disorders. This core will be utilized by the projects as follows. Project #1: Aim #1: Perform genomic (RNA expression on microarrays) studies on blood from children with autism in the 4-9 year old range, and compare to the blood genomic profiles we have obtained in children with autism in the 2-5 year old age range. Aim #2. Compare gene expression as a function of blood metal levels in both age groups in A, A-R, ASD, MR/DD and GP groups. Aim #3. Examine genomic profiles in pregnant mothers who have previously given birth to an autistic child to determine if there is a specific genomic profile that correlates with whether the mother’s fetus is destined to develop autism. Project #2. Aim #1. Describe the gene expression profiles in the blood using specific white blood cell subsets including NK cells for children with autism without regression, autism with regression, and ASD children compared to GP and delayed children. Aim #2. Examine gene expression following stimulation or activation of specific white blood cell subsets of A, A-R, ASD, MR/DD and GP children with: low level mercury; immune cell stimulation/activation with vaccine antigens and cell-specific mitogens; and xenobiotics. Project #3. Compare gene expression profiles in the blood of children with autism to the blood of experimental animals exposed to toxicants including organic mercury, PCB 95, and PBDE 47 (Project #3).

NIH Spending Category:
autism; Biotechnology; Brain Disorders; Genetics; Mental Health; Mental Retardation (Intellectual and Developmental Disabilities (IDD)); Pediatric

Project Terms:
5 year old; 9 year old; Accounting; Age; age group; Animals; autism spectrum disorder; autistic Children; Autistic Disorder; Autoantibodies; base; Behavioral; Birth; Blood; Blood specimen; cell type; Cells; chemokine; Child; Core Facility; cytokine; Data; Developmental Delay Disorders; Disease; Environmental Health; Fetus; Gene Expression; General Population; Genes; Genetic; Genetic Transcription; Genome; Genomics; Human; Immune; immune function; Inherited; Language; Leukocytes; Mental Retardation; Mentally Disabled Persons; Mercury; Metals; Mitogens; Molecular; Molecular Profiling; Mothers; Natural Killer Cells; Pathway interactions; Patients; pentabromodiphenyl ether; peripheral blood; Phenotype; Polychlorinated Biphenyls; Population Group; pregnant; Principal Investigator; Process; programs; Resources; Reverse Transcriptase Polymerase Chain Reaction; RNA Processing; Running; Scanning; Subgroup; Surveys; Toxic Environmental Substances; toxicant; vaccine Antigen; Xenobiotics

THE CHARGE STUDY: CHILDHOOD AUTISM RISKS FROM GENETICS AND THE ENVIRONMENT

Abstract Text:
DESCRIPTION (provided by applicant): Few rigorous epidemiologic studies have addressed the environmental causes and biologic underpinnings of autism spectrum disorder (ASD). The CHARGE (Childhood autism Risks from Genetics and Environment) Study is a large, population-based case-control investigation of environmental risk factors, broadly defined, in relation to ASD and developmental delay without ASD symptoms, with referents from the general population. Fieldwork began in 2003, and by now CHARGE has published widely on exposures such as air pollution, mercury, flame retardants, maternal nutritional status in the peri-conception, untreated fever during pregnancy, mitochondrial dysfunction, candidate genes, a wide array of functional immune markers in both the child and the mother, and maternal metabolic conditions including obesity and diabetes. This last finding is notable, given the epidemic of obesity and type 2 diabetes that has occurred in parallel with the steady rise in ASD over the last few decades. Moreover, an emerging literature implicates several endocrine disrupting chemicals as contributing to obesity and metabolic dysregulation, including hyperinsulinemia, and to neurodevelopmental disorders as well. This project therefore builds upon these observations in several ways. First, obesity and type 2 or gestational diabetes will be examined in a larger sample, and glucose challenge test (GCT) results for the first time, to determine associations not only with development of ASD and intellectual impairment in the children, but also with specific speech and language delays, behavioral phenotypes such as attention deficits or hyperactivity, and gene expression. Second, these maternal metabolic conditions will be evaluated for associations with markers of both metabolic and immune dysregulation to be measured in neonatal bloodspots. Third, the predictive value of neonatal bloodspot markers for a later diagnosis of ASD or other child developmental and behavioral outcomes will be assessed. Fourth, the maternal metabolic conditions will be analyzed for potential links with upstream exposures to phthalates and anti- bacterial compounds, ubiquitous chemicals in common household products. Finally, this project will examine how gene variants that play a role in biochemical pathways relevant to the processes under study may influence susceptibility of the mother, the neonate or the child. To ensure adequate power for this analysis of gene-environment interaction, the sample size will be increased to 2400 children. This project addresses several goals set by the NIH Interagency autism Coordinating Committee: 1) to discover environmental factors contributing to ASD, particularly in the prenatal period, 2) to understand biological mechanisms for ASD risk, including gene-by-environment interactions, and 3) to identify children at risk for ASD at earlier time points. Results of this detailed inquir into early exposures, maternal pathophysiology and prognostic markers in the newborn will set the stage for developing prevention strategies.

Public Health Relevance Statement:
PUBLIC HEALTH RELEVANCE: This project addresses several issues of direct public health relevance, and the science to be produced will lead to benefits in a wide cross-section of the U.S. population. Because obesity is reaching epidemic proportions and other metabolic conditions such as Type 2 diabetes, gestational diabetes, and dyslipidemia are rising steeply, understanding environmental causes has tremendous public health potential for moving us closer to effective prevention strategies. If environmental chemicals used in common household products do prove to adversely affect body weight, measures can be taken to either reformulate those products, removing them from the market, or to educate consumers on how to avoid them. Similarly, steady increases in ASD might be curbed if the postulated causal pathway is supported by the evidence.

NIH Spending Category:
autism; Behavioral and Social Science; Brain Disorders; Clinical Research; Diabetes; Genetic Testing; Genetics; Intellectual and Developmental Disabilities (IDD); Mental Health; Neurosciences; Nutrition; Obesity; Pediatric; Perinatal Period – Conditions Originating in Perinatal Period; Prevention

Project Terms:
Address; Affect; Age; aged; Air Pollution; Anti-Bacterial Agents; Attention; autism spectrum disorder; Autistic Disorder; Behavior; Behavioral; Biochemical Pathway; Biological; Biological Markers; blood glucose regulation; Body Weights and Measures; C-Peptide; Candidate Disease Gene; case control; CCL2 gene; chemical association; Chemicals; Child; Childhood; Conceptions; cytokine; Data; Development; Developmental Delay Disorders; Diabetes Mellitus; Diagnosis; disorder risk; Dyslipidemias; Endocrine Disruptors; Ensure; Environment; environmental chemical; Environmental Risk Factor; Epidemic; Epidemiologic Studies; ESR1 gene; Exposure to; Fever; Flame Retardants; Functional disorder; gene environment interaction; Gene Expression; General Population; Genes; Genetic Risk; Gestational Diabetes; Glucose; glucose metabolism; Goals; high risk; Household; Household Products; human TNF protein; Hyperactive behavior; Hyperinsulinism; Hypertension induced by pregnancy; Immune; immune function; Immunologic Markers; Impairment; inattention; Inflammation; Inflammatory; Insulin Resistance; insulin sensitivity; interest; Interleukin-6; Investigation; Language Delays; Lead; Leptin; Link; Literature; Marketing; Maternal Exposure; Measures; mercury; Metabolic; Metabolic Marker; Metabolism; mitochondrial dysfunction; Mothers; Neonatal; neonate; neurodevelopment; Neurodevelopmental Disorder; Newborn Infant; Non-Insulin-Dependent Diabetes Mellitus; Nutritional status; Obesity; Outcome; Pathway interactions; Phenotype; phthalates; Play; Population; population based; PPARG gene; Predictive Value; Predisposition; Pregnancy; prenatal; Prevention strategy; Process; prognostic; Prognostic Marker; public health medicine (field); public health relevance; Publishing; Regulation; Risk; Role; RORA gene; RPL10 gene; Sample Size; Sampling; Science; Self Care; Speech Delay; Staging; Symptoms; Test Result; Time; Triclosan; Tumor Necrosis Factor-alpha; United States National Institutes of Health; Variant; Variation (Genetics)

PRENATAL TIMING OF HEAVY METAL EXPOSURES FROM AUTISTIC AND NON-AUTISTIC CHILDREN

DESCRIPTION (provided by applicant): Little is known about the etiology or risk factors for autism, a disease affecting 1 in 50 children in the U.S. While genetic and environmental factors are thought to act together, the specific mechanisms are not known and the measurement of environmental risk factors during critical periods of neurodevelopment has been lacking. This case-control study seeks to apply a novel dental biomarker of early life metal exposure, including in utero, to identify risk factors for ASD. Beyond looking at exposure intensity, we will be able to identify differences in exposure timing between cases and controls. This will allow us to identify critical windows when exposure, even at low levels, increases the risk of ASD. Using the proposed biomarker, we will directly assess fetal exposure, and will not rely on maternal biomarkers which may only provide an indirect measure of fetal exposure to metals. This work will have substantial impact on epidemiologic investigations of the relation of early life chemical exposures to ASD and other neurodevelopmental disorders as it can be used to objectively reconstruct both exposure intensity and timing.

Public Health Relevance Statement:
PUBLIC HEALTH RELEVANCE: Little is known about the causes of autism. This proposal seeks to apply a novel dental biomarker of early life metal exposure, including in utero, to identify risk factors for ASD. Beyond looking at exposure intensity, our application is novel in that we will be able to identify differences in exposure timing between cases and controls. This will allow us to identify critical windows when exposure, even at low levels, increases the risk of ASD.

Project Terms:
Accounting; Address; Affect; Aluminum; analytical method; Animals; Apatites; Arsenic; autism spectrum disorder; autistic Children; Autistic Disorder; Binding (Molecular Function); Biological; Biological Markers; bone; Cadmium; Calcified; Calcium; case control; Case-Control Studies; Chemical Exposure; Chemicals; Child; Childhood; Chromium; critical period; Data; deciduous tooth; Dental; Dentin; Development; Disease; early life exposure; Elements; Environment; Environmental Exposure; Environmental Risk Factor; Epidemic; Epidemiologic Studies; Etiology; Exposure to; fetal; Fetus; Genes; Genetic; Health; Heavy Metals; Human; Immune system; in utero; Investigation; Lead; Life; Literature; longitudinal design; Manganese; Measurement; Measures; mercury; Metal exposure; Metals; Methodology; Methods; mineralization; Mothers; neurodevelopment; Neurodevelopmental Disorder; Nickel; novel; Perinatal; Perinatal Exposure; Play; postnatal; Predisposition; Pregnancy; prenatal; Property; prospective; public health relevance; Recording of previous events; repository; Risk; Risk Factors; Role; Sampling; skeletal; Staging; Time; Tissues; Tooth structure; Toxic Environmental Substances; toxicant; Toxicant exposure; Work

comment on: Childhood vaccine beliefs reported by somali and non-somali parents.

14 Jul

Autism in the U.S. Somali Community has gathered significant attention in recent years (as has autism in other Somali communities outside of Somalia, for example in Sweden). Most of the attention in the U.S. can be traced back to vigorous advocacy by people like my fellow IACC public member Idil Abdul. Not all attention is good. For example, Minnesota Somali parents received a lot of attention from groups promoting the failed vaccine/autism link. When news of the possibly high prevalence in the Minnesota Somali community arose, David Kirby used the story to promote the idea of vaccines causing autism. Generation Rescue brought in Andrew Wakefield to talk to Somali parents in closed door meetings.

With the discussion of vaccines and autism comes fear and with fear of vaccines comes a reduced uptake. One recent story reports that the MMR uptake in the Minnesota Somali community dropped from 90% to 54% in the past 10 years. Sadly, that same story discusses how the Minnesota Somali community is presently involved in one of the largest measles outbreaks in recent history.

The question is, what are the views of the Somali community on vaccines and autism? To answer that, a new study has just been released: Childhood vaccine beliefs reported by somali and non-somali parents. (note the lack of capitalization of Somali is in the original). The full paper is available online.

There are limitations to the study, such as the use of a “convenience sample” of parents attending one specific clinic. This could induce bias. Also, the response rate was about 50%. This is reasonable, but again some bias might be involved in who actually responded. People who distrust vaccines might distrust those performing the survey, for example.

To answer the question–yes, Somalis in Minnesota do think that the MMR causes autism more than their non-Somali counterparts. Nearly 5 times more likely. But, the majority do not believe–about 35% of Somali parents and 8% of non-Somali parents believe that autism is caused by vaccines.

At recent IACC meetings, Idil Abdul has related how she knows Minnesota Somali families who stopped vaccinating after having a first autistic child. These families went on to have more autistic children. Unvaccinated autistic children. In one family, she relates a family with 5 autistic children.

This stands as an example of where we in the autism parent community have failed. We scared the parents in the Minnesota Somali community, sending in Generation Rescue, Andrew Wakefield and David Kirby. Parents stopped vaccinating, offering zero protection from autism but leaving their children open to infectious diseases. To say nothing of the guilt that parents feel and the children who grow up under that falsely placed guilt.

Yes, I stand apart from the minority of parents spreading the message of a vaccine-epidemic. But, as a community, we have to accept our failures as a community. And this is an example of a big failure.

Here is the abstract.

Abstract

BACKGROUND:

In 2011, an outbreak of measles in Minnesota was traced back to an unvaccinated Somali child. The purpose of this project was to (1) ascertain whether Somali parents are more likely than non-Somalis to refuse childhood vaccinations, particularly the measles-mumps-rubella (MMR) vaccine and (2) determine what factors influence the decision not to vaccinate.

METHODS:

We explored parental perceptions and utilization of vaccines through a survey distributed to a convenience sample of Somali and non-Somali parents of children ≤5 years old in a family medicine clinic in Minneapolis, MN.

RESULTS:

A total of 99 surveys were completed, 28% (n = 27) by Somali parents. Somali parents were more likely than non-Somali parents to have refused the MMR vaccine for their child (odds ratio, 4.6; 95% confidence interval, 1.2-18.0). Most of them refused vaccines because they had heard of adverse effects associated with the vaccine or personally knew someone who suffered an adverse effect. Somali parents were significantly more likely to believe that autism is caused by vaccines (35% vs. 8% of non-Somali parents). Somalis were also more likely to be uncomfortable with administering multiple vaccines at one visit (odds ratio, 4.0; 95% confidence interval, 1.4-11.9) and more likely to believe that children receive too many vaccines.

CONCLUSIONS:

Statistically significant differences in perceptions and use of vaccines were reported by Somali and non-Somali participants. Somali parents are more likely to believe that the MMR vaccine causes autism and more likely to refuse the MMR vaccine than non-Somali parents. These beliefs have contributed to an immunization gap between Somaliand non-Somali children


By Matt Carey

Comment on: Immunization uptake in younger siblings of children with autism spectrum disorder.

10 Jul

While doing a bit of reading for a recent article: A study comparing vaccinated and unvaccinated kids is coming…and SafeMinds is concerned, I ran across this abstract: Immunization uptake in younger siblings of children with autism spectrum disorder.

What did they find? That parents often delayed vaccines for younger siblings of autistic kids. And that this made no difference on the autism rate in those younger siblings. In fact, most of the younger siblings with ASD diagnoses were not fully immunized.

This isn’t a study of just MMR or just thimerosal. It’s all vaccines. In online autism/vaccine discussions, you will often read something to the effect of “only one vaccine and one ingredient have been studied”. Wasn’t true before this new study. Isn’t true now. Will be even less true when the next study comes out.

Why do I suspect that “Dr. Bob” Sears, SafeMinds, Generation Rescue, the National Autism Society and TACA won’t include this study in the literature they bring to parents’ attention?

Background: Parental concerns persist that immunization increases the risk of autism spectrum disorder, resulting in the potential for reduced uptake by parents of younger siblings of children with autism spectrum disorder (“younger sibs”). Objective: To compare immunization uptake by parents for their younger child relative to their older child with autism spectrum disorder (“proband”) and controls.

Design: Immunization status was obtained for 98 “younger sibs,” 98 “probands,” and 65 controls.

Results: A significant group difference emerged for overall immunization status (Fisher’s exact test = 62.70, p < .001). One or more immunizations in 59/98 younger sibs were delayed (47/98; 48%) or declined (12/98; 12.2%); immunizations were delayed in 16/98 probands (16.3%) and declined in only one. All controls were fully immunized, with only 6 (9.2%) delayed. Within the "younger sibs" group, 25/98 received an autism spectrum disorder diagnosis; 7 of whom (28%) were fully immunized. The rates of autism spectrum disorder diagnosis did not differ between immunized and nonimmunized younger sib groups, although small sample size limits interpretability of this result.

Conclusion: Parents who already have one child with autism spectrum disorder may delay or decline immunization for their younger children, potentially placing them at increased risk of preventable infectious diseases.


By Matt Carey

Comment on “Prenatal and neonatal peripheral blood mercury levels and autism spectrum disorders”

3 Jul

About a decade ago (even longer) there was a question posed as to whether thimerosal (a mercury containing preservative) in vaccines could increase the risk of autism. Many studies have been performed and the answer is no (for example, here).

Even though the question has been approached from multiple angles, research continues. A study out this week takes a look at blood mercury levels in the mother and newborn baby to see if they are correlated with later autism diagnoses in the baby.

California archives blood samples from pregnant mothers and blood spots (cards with a dried spot of blood) from newborns. A team looked at these samples to explore the question: are blood mercury levels in pregnant mothers or newborns correlated with autism.

Short answer: no.

Add this to a MIND Institute study from a few years ago , (Blood mercury concentrations in CHARGE Study children with and without autism) which showed no differences in blood mercury levels between ASD and non ASD preschool children when controlled for diet. And this study from Jamaica again showing no differences. So, while the authors in the recent study suggest a larger study would be valuable, I question whether resources would be wisely spent in that way.

The abstract is below of the new study is below:

Prenatal and neonatal peripheral blood mercury levels and autism spectrum disorders.

BACKGROUND:

Prenatal and early-life exposures to mercury have been hypothesized to be associated with increased risk of autism spectrum disorders (ASDs).

OBJECTIVES:

This study investigated the association between ASDs and levels of total mercury measured in maternal serum from mid-pregnancy and infant blood shortly after birth.

METHODS:

The study sample was drawn from the Early Markers for Autism (EMA) Study. Three groups of children who were born in Orange County, CA in 2000-2001 were identified: children with ASD (n=84), children with intellectual disability or developmental delay (DD) (n=49), and general population controls (GP) (n=159). Maternal serum specimens and newborn bloodspots were retrieved from the California Department of Public Health prenatal and newborn screening specimen archives. Blood mercury levels were measured in maternal serum samples using mass spectrometer and in infant bloodspots with a 213nm laser.

RESULTS:

Maternal serum and infant blood mercury levels were significantly correlated among all study groups (all correlations >0.38, p<0.01). Adjusted logistic regression models showed no significant associations between ASD and log transformed mercury levels in maternal serum samples (ASD vs. GP: OR [95% CI]=0.96 [0.49-1.90]; ASD vs. DD: OR [95% CI]=2.56 [0.89-7.39]). Results for mercury levels in newborn blood samples were similar (ASD vs. GP: OR [95% CI]=1.18 [0.71-1.95]; ASD vs. DD: OR [95% CI]=1.96 [0.75-5.14]).

CONCLUSIONS:

Results indicate that levels of total mercury in serum collected from mothers during mid-pregnancy and from newborn bloodspots were not significantly associated with risk of ASD, though additional studies with greater sample size and covariate measurement are needed.

Copyright © 2014 Elsevier Inc. All rights reserved.


By Matt Carey

The vaccine-autism notion as a liability

1 Jul

It wasn’t that long ago that my kid was diagnosed and I started on the search for information about autism. At that time the idea of vaccine causation was dominating the discussion, at least in the online world where autism parents were participating. Even mainstream news outlets seemed to think that getting a “balance” viewpoint from a parent espousing vaccine causation was necessary. Over the past near-decade the discussion landscape has changed a great deal. Sure, a small group of parent-activists (and non-parents using autism as a tool to attack vaccines) still present a vocal minority telling us about how vaccines cause autism. But for the most part the discussion has moved on from vaccines.

To use a simple example: a few years ago Jenny used the idea of vaccines causing autism as a springboard back into the public’s eye. These days, she’s quiet and even trying to distance herself from her previous statements.

As a more detailed example, Consider SafeMinds:

In 2006, SafeMinds endorsed the Combating Autism Act. In their endorsement at that time, SafeMinds mentions vaccines 25 times.

In 2011, the Combating Autism Act was up for reauthorization. >A coalition of vaccine focused autism parent organizations including SafeMinds was formed. They included in their statement “The membership includes advocates of the vaccine theory”. Right out there and public.

This year, 2014, we see a different coalition formed that includes SafeMinds: the Autism Policy Reform Coalition. Many of the groups in the new coalition were part of the 2011 coalition, and all of the APRC’s member organizations have a strong focus on vaccines as causing autism. But here’s the difference: there appears to be no mention of the word “vaccine” on the >APRC’s website. (here’s my Google search).

SafeMinds is still very clear on their position at their own website. A recent article make that clear: Dear Parents, you are being deceived about vaccines and autism.

There’s no mention of the word “vaccine” on the >SafeMinds announcement of the new Coalition.

Consider Generation Rescue. Their original website was all about how mercury in vaccines was the cause of autism. Autism was a “misdiagnosis” for mercury poisoning. That was 2005. A few years later, Jenny McCarthy became a spokesperson for, then president of Generation Rescue. The GR website proudly proclaimed, “Jenny McCarthy and Jim Carrey’s Autism Organization” and was, again, all about vaccines. Jenny McCarthy led a few hundred people in a march in Washington DC solely focused on vaccines: Green Our Vaccines Rally. She went on talk shows telling the public that we need to get the “sh*t” out of vaccines. Today? The Generation Rescue website hasn’t completely lost the discussion of vaccines, but has toned down a great deal. She wrote an op-ed for the Chicago Sun Times Jenny McCarthy: The gray area on vaccines.

As an aside–I have a hard time being lectured by Jenny McCarthy about “critical thinking” as she tries to do in her Sun-Times op-ed.

Recently the National Autism Association (another member of the coalition opposing the autism research reauthorization) ran into trouble in a fundraiser. When their views on vaccines and autism were made very, very public, Chili’s cancelled a fundraiser with them. The NAA responded:

Though NAA has changed our mission and efforts in recent years to focus on autism safety, namely wandering prevention, controversial views about vaccines remained on our website. Because of guest feedback about these views, Chili’s has opted to cancel tomorrow’s event. We respect their decision and ask everyone to please speak words of love and kindness.

The NAA felt that they needed to distance themselves from their older “controversial views”. At least that’s what they said. It’s worth noting that the NAA has not changed their website on those controversial views.

Three groups. All historically major players in promoting the failed autism/vaccine hypotheses. As a coalition, they avoid mention of the word. As separate entities, they still espouse the ideas to varying degrees. Some have mixed messages–for example telling us that they previously held “controversial” views while not changing those views.

Things have changed. The vaccine debate has shifted and largely dropped in prominence and acceptance. It’s now a liability. A political and public relations liability. Even the groups promoting vaccine-causation appear to understand this. I welcome this shift. Besides being wrong and diverting a great deal of attention into fruitless areas of research, the groups dominating the discussion with vaccine causation caused a lot of harm over the years. I just wish they would truly change their views and admit their mistakes.


By Matt Carey

Andrew Wakefield and Lance Armstrong: two unethical people exposed by the Sunday Times

30 Jun

The Sunday Times has a series of films (Unquiet Films, www.foreverunquiet.co.uk) has a series of short films about the impact of The Times has had over the years.

Newspapers are all about stories – but sometimes the best stories are the ones we don’t tell.

Let’s not forget that news is often something that someone, somewhere, doesn’t want you to know. The real-life tales of how world-changing exclusives – whether from foreign reporters under fire, or determined hacks banging against stone-walling bureaucracy – are brought out into the open can be just as extraordinary as the articles that end up in the newspaper. Sometimes the story behind our amazing photo-journalism, campaign to change the law on adoption, to make cities safe for cycling, to reveal the corruption at the heart of FIFA, or the lies of a champion like Lance Armstrong are as exciting as a thriller, as tense as an episode of House of Cards.

We decided it was time to showcase just what the best journalists do… the real lives, real struggles, real bravery behind the newspaper stories that change the course of history. It’s all very well to boast that The Times and the Sunday Times strive to speak truth to power, without fear or favour and to report the truth, whatever the cost. But too often exactly what that takes – the death threats to reporters, the legal battles, the toughness and integrity it takes to get the article on the page – gets lost in the telling.

So here, in a series of extraordinary and independently made short films are some of the amazing, true-life stories behind the stories – we hope you find them as moving and inspiring as we do.

As an example of the “best journalists do”, they have a segment entitled “question everything“. It focuses on Brian Deer (whose work exposed the unethical actions of Andrew Wakefield, later found proved by the GMC) and David Walsh (who pursued and uncovered the Lance Armstrong doping scandal).

From BAFTA-winning filmmaker Will Clark: We now live in a world where more often than not, only the surface facts of a story are reported. Real investigative journalism seems to be a dying art and I feel this is something we should all be deeply concerned about. I wanted to create a film that focused on two Sunday Times journalists whose pursuit for the truth turned into an obsession. From Lance Armstrong’s doping revelations to Andrew Wakefield’s fraudulent MMR claims, both were lengthy investigations that were published at risk by the newspaper. Both investigations also managed to reveal large scandals that would most likely have remained hidden were it not for the perseverance and tenacity of the journalists covering the stories. I’m sure every reporter has secretly wished for his or her very own All The President’s Men moment. This is the tale of two journalists who got their wish.

Here’s the video:


By Matt Carey

Same old Jenny

27 Jun

Jenny McCarthy is back in the news. It appears that The View is not renewing her contract. In fact, there seems to be quite a shakeup at The View with many people leaving.

Jenny McCarthy is responding to this news, discussing fellow View host Sherri Shephard as picked up by Fox News.

“If Sherri goes … I go too,” McCarthy tweeted Thursday from her verified account, adding “#sisters,” followed by another tweet: “My View will be changing too. As will with many hard working folks. Thanks to everyone at the show for your dedication and an amazing year.”

Interesting spin there–instead of being released, she’s framing it as Jenny McCarthy, ready to take a stand and quit her job for her “sister”. Right. One thing I’ve learned over the years watching Jenny McCarthy, she’s good at spinning things to make herself look good.

She’s been a bit of a chameleon when it comes to her opinions. When it comes to autism, she started out with a new-age type “indigo child” approach. Then she took on the “vaccines cause autism” thing, which really catapulted her back into the public eye. Then the vaccine thing became a liability and she got quiet, finally posting an op-ed distancing herself from her previous views*. And, now, we see that the “View” she’s had for the past year was, well, just for “The View”. New job, new View. Will that involve autism, vaccines or something new? We don’t know. We just know that leaving the show means she can change her views.

Same old Jenny.


By Matt Carey

*Jenny McCarthy in her op-ed:
“I’ve never told anyone to not vaccinate.”

I don’t know if that’s true or not. I know she fueled a movement away from vaccines. For example, she wrote on Oprah Winfrey’s website in 2007, “But if I had another child, I would not vaccinate.” Yep, she has technical truth. She didn’t say, “you don’t vaccinate”. She just put herself out there as a leader of a community and said, “I won’t vaccinate”.

You know what word you won’t find in her Op-Ed? Autism. She doesn’t even approach the question that made her famous and that put so much fear in parents. It’s a very politically crafted article, in my opinion.

Jenny McCarthy on Larry King Live:

We’re scared. I mean moms and pregnant women are coming up to me on the street going, I don’t know what to do. I don’t know what to do. And I don’t know what to tell them, because I am surely not going to tell anyone to vaccinate. But if I had another child, there’s no way in hell.

She won’t tell someone *not* to vaccinate, but she “surely” won’t tell some one to vaccinate.

And later on Larry King Live

KING: Isn’t the problem here, Jenny, that people sometimes listen with one ear are going to panic. And not vaccine at all?

MCCARTHY: Probably. But guess what? It’s not my fault. The reason why they’re not vaccinating is because the vaccines are not safe. Make a better product and then parents will vaccinate.

Right. She gives people incorrect information about the safety of vaccines, they get scared and don’t vaccinate, but it’s not her fault because she’s on record saying (but not acting) she’s pro vaccine.

Another time on Larry King Live

MCCARTHY: We get that they’re saving lives, but the increase is ridiculous, you guys. Look, it’s plain and simple. It’s bull (EXPLETIVE DELETED).

KARP: No, it’s not.

MCCARTHY: Too many shots too soon.

(CROSS TALK)

MCCARTHY: My son died in front of me due to a vaccine injury. And there are many — every week I get a picture of a dead child.

KING: You lost a son?

MCCARTHY: Evan died in front of me for two minutes, cardiac arrest. Every week, I get a picture sent to me of a child that died following a vaccination.

What are parents supposed to think when they hear her say that vaccines kill, and that there are “too many, too soon”? Seriously, if there are “too many” vaccines, are parents supposed to say, “Jenny McCarthy is pro-vaccine. I’ll vaccinate my kid!” Too many means some vaccines shouldn’t be given which means, don’t vaccinate with those vaccines.

But, Jenny McCarthy doesn’t want you to think that’s what she said.

UK families suing MMR litigators for pursuing “hopeless” claims

27 Jun

The saga of the U.K. MMR litigation continues. In this case a family is suing a law firm involved for mishandling the case. Per one story, one of the original MMR litigants (McCafferty) is now suing:

McCafferty, 23, from Falkirk, central Scotland, is seeking damages to “include compensation, distress, expense and inconvenience of engaging in hopeless litigation”.

I’m not sure how sound this case is, but here we have a family arguing that they suffered by being sucked into the MMR litigation. The effort and expense they put into the case was not only wasted, but the case was “hopeless” and, thus, the attorneys were at fault for dragging them through this.

The story at The Times is behind a paywall, but it starts:

MMR families sue their legal aid lawyers

Families who failed to win compensation cases driven by flawed research into the MMR vaccine are suing their lawyers for pursuing “hopeless” claims and enriching themselves on legal aid.

Matthew McCafferty, 23, who received the vaccine and three years later developed autism, is taking action against his former legal team over a claim that he says had no chance of succeeding, was issued out of time and raised false hopes

MMR vaccine: lawyers sued for pursuing claim based on link to autism
Man claims Hodge Jones & Allen was negligent in litigating a hopeless claim while profiting from part of £15m legal aid funding

A man is suing his former legal team for pursuing “hopeless claims” based on flawed research into the MMR vaccine, it has emerged.

Matthew McCafferty, who was diagnosed with autism three years after receiving the vaccine, is taking legal action over a legal claim that he says had no chance of succeeding, according to a report in the Times.

The law firm is Hodge Jones & Allen. In MMR and Autism: What Parents Need to Know, Michael Fitzpatrick discusses how Richard Barr, the attorney who worked closely with Andrew Wakefield, started at Dawbarns, moved to Hodge Jones & Allen and then moved on to Alexander Harris, “always taking his burgeoning portfolio of MMR cases with him.”


By Matt Carey

Andrew Wakefield, apparently he’s making films to convince you that doctors think vaccines cause autism and are covering it up.

28 May

It can be very interesting to hear what people say when they are in their home element. Ken Reibel showed this when he reported back from an AutismOne parent convention six years ago. More recently, we heard Jenny McCarthy accuse parents who don’t take her advice on alternative medicine of being victim moms who love the attention they get from having a disabled child. So much so that they won’t treat their children. So, with that in mind, I took the time to listen to a talk from this year’s AutismOne convention. The talk by Andrew Wakefield.

Andrew Wakefield, the doctor behind the MMR/autism scare of the 1990’s, spoke at the AutismOne parent convention last week. His talk at AutismOne was The Legacy of Vaccine Injury. It’s much of the same non-autism talk about vaccines one reads online. But one minute of the talk stood out for me. A minute where he describes why he is making films.

Yes, in case you weren’t aware, Mr. Wakefield has a new career as a film maker. He has a documentary on the death of an autistic young man, Alex Spourdalakis. Mr. Spourdalakis was brutally murdered by his mother and caregiver. Mr. Wakefield, as it turns out, had been “helping” the family and was filming their story. That film is finished. Mr. Wakefield tells us why he makes his films in his AutismOne talk. One might ask: is it to demonstrate the needs of autistics? The challenges parents of autistics face? The lack of supports for autistics?

No. It’s best to get it straight from him (although I admit the title of this article gives it away). With that in mind, here’s my best effort at transcribing what he says. For context: he’s speaking to an audience of autism parents at AutismOne, and he’s been talking about how surveys/studies show a sizable minority of the U.S. population believes that vaccines cause autism:

“And there is no mention in these studies of the uncertain or the undecided. There was another poll* that came out, I think from the University of Chicago, in fact. Where they asked the question: ‘Do you believe doctors think that vaccines cause autism and are covering it up?’ 20% of the respondents said yes. The important number is that 36% didn’t know. And it’s that 36% that I am targeting in the films that I am making. They are not for you. You already know. I’d be honored if you watched them but they are not for you. They are for the agnostic. And for that reason they must get out into the mainstream.”

For that reason they must get out into the mainstream

“That reason”: convincing the agnostic that doctors think that vaccines cause autism and they are covering it up. Alex Spourdalakis died a horrific death, and that can be used in this campaign, by inserting him into one of Mr. Wakefield’s films.

Go ahead and listen. It’s about 9 minutes in this video (for some reason the embed code isn’t working so you have to follow the link).

And some people wonder why I am critical of Mr. Wakefield. Yeah, I know that criticizing Mr. Wakefield plays directly into the persona he has created, where he has given everything for the children. But in this case the time as well as the criticism is well deserved.


By Matt Carey

*In case you are wondering: he appears to be referring to Medical Conspiracy Theories and Health Behaviors in the United States.

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