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Autism Spectrum Disorders

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Autism spectrum disorders (ASDs) are a group of complex neurodevelopmental conditions characterized by impairments in interpersonal communication and social interaction, and repetitive behaviors.  The purpose of this research is to provide the relevant background literature and extensive epidemiological study to educate parents who are concerned about thimerosal-containing vaccine and mumps, measles and rubella (MMR) vaccine to be causally associated with autism and/or ASD.  Extensive epidemiological studies have shown that neither thimerosal nor MMR vaccines cause autism. 

“These studies have been performed in several countries by many different investigators who have employed a multitude of epidemiologic and statistical methods” (Gerber et al. 2009). In this research, one will look at autism at large, its prevalence, the MMR vaccine and its relation to diagnosis of ASDs as well as a meta-analysis of the MMR vaccine. The study goes a head to provide an epidemiological study and a retrospective study together with methods and findings of two studies. Social issues that have come up, as well as beliefs in vaccination, have also been tackled in this study. Parents of children with ASD have not been left out as well.    

Autism has become a common disease in children all over the United States in the recent past; it is believed that 1 out 110 children are diagnosed with the disease and, therefore, immensely crucial to understand is the disease at large and the current status. This will help parents with kids who have autism to understand what they are dealing with and how they can adapt to the situation. Vaccination is also a big step to prevent occurrences in children and, therefore, parents to be will benefit immensely from the information of various vaccines that are available. (Baker, 2008)

"Vaccines for MMR in children" 

In the current investigation, Hodson, Mateu et al (2012), sought to statistically reinvestigate the relationship between MMR vaccinations and ASD diagnosis as reported in the Cochrane Collaboration’s “Vaccines for MMR in children” and in primary studies (Demicheli et al. 2005).  From the Cochrane research review, evidence of adverse events from MMR vaccines was reported, but the review’s authors did not present the statistical confirmation of the existence, or not of a reliable relationship between MMR vaccination and ASD diagnoses.  The purpose of the study was to systematically examine the statistical evidence between MMR vaccinations and diagnosis of ASD.  Authors of the study sought, through a meta-analysis of primary studies, to address the question: “Are odds of being diagnosed with an ASD the same for those who receive an MMR vaccination and those who do not?” 

Methods: Three researches searched for and obtained relevant studies, and two researches independently applied a standardized data extraction form to the included studies.

Results: 7 independent effect sizes have been calculated, having pooled random effects OR-0.25 (95% CI, LL=0.09, UL-0.76), and under the fixed effect model, the OR-0.33 (95% CI, LL-0.25, UL=0.45).

Conclusion:  Under a hypothesis of equivalence, odds of ASD diagnosis attributable to receiving or not receiving an MMR vaccination are deemed indistinguishable (i.e., equivalent) if observed odds ratios (Ors) were within the clinical limit of indifference.  Even so, odds of ASD diagnosis are substantially smaller for those receiving an MMR vaccination than for those who do not.

Taylor, Miller and et al. (1999) undertook an epidemiological study to investigate whether MMR vaccine may be causally associated with autism. 

Methods: Children with autism born since 1979 were identified from special needs/disability and special schools in eight North Thames health districts, UK.  Information from clinical records was linked to immunization data held on the child’s medical record.  In their study, investigators looked for evidence of a change in trend in incidence or age at diagnosis associated with the introduction of MMR vaccination to the UK in 1988.  The clustering of onsets within the defined post-vaccination period was studied by the case-series method.

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Findings: 495 cases of autism were identified.  In 293 cases, the diagnosis was confirmed using the criteria of the International Classification of Diseases tenth revision (ICD10).  They had been noticed a steady increase in such cases by the year of birth with no abrupt “step up” or modification in the trend line right after the introduction of the MMR vaccination.  Moreover, there was no difference in the age at the diagnosis between cases in which there was a vaccination after or before 18 months of age and in those with no vaccination.  Also, there was not any temporal association between the onset of autism with 1-2 years after the vaccination with the MMR (the relative incidence compared to control period 1.09 [0.79-1.52] and 94 [95% CI 0.60-1.47]). The developmental regression was not noticed in months after the vaccination (the relative incidence within 2 and 4 months after the MMR vaccination 1.00 [0.52-1.95] and 0.92 [0.38-2.21].

Conclusion of the study: Taylor, Miller and et al. (2009) concluded that the analysis did not approve of a causal association between the autism and MMR vaccine.

Smeeth, Cook, Fombonne et al. conducted a study aimed to assess whether the MMR vaccination is connected with the increased risk of autism or some other pervasive developmental disorders.

Methods:  The matched case-control scientific work using the UK General Practice Research Database.  Cases were people born in 1973 or later who had first recorded diagnosis of pervasive developmental disorder (PDD) while registered with a contributing general practice between 1987 and 2001.  Controls were matched on the sex, age,  and general practice.

Findings: 4469 controls and 1294 cases were included.  1010 cases (which are 78.1%) had the vaccination of MMR recorded before diagnosis, comparing to 3671 controls (which are 82.1%) before the age when their matched cases were diagnosed. After the adjustment for age at joining the database, odds ratio for association between MMR and PDD was 0.86 995% CI 0.68-1.09).  Findings were similar, when restricted to children with diagnosis of autism, to those vaccinated with MMR before the third birthday, or to the period before media coverage of the hypothesis linking MMR to autism.

Results:  The case-control study suggested that MMR vaccination is not associated with an increased risk of PPD/autism.Childhood vaccination has been one of the most essential advances in medicine in the 20th century.  Fombonne (2008) in his study points out that “unfortunately, once vaccine programs have been successful at controlling preventable infectious diseases, people shift their attention to the potential adverse effects on vaccines (which are rare, but can, nevertheless, be serious).  Deaths of young children occurred in Europe because of the MMR-autism scare, and as shown in a recent US measles outbreak, children’s health was put at risk because of the suppose vaccine-autism link”.

The prevalence of autism has risen dramatically over the past 10-15 years in the United States, and estimates indicate that 1 in 110 children are diagnosed with autism spectrum disorder (ASD Centers for Disease Control and Prevention, 2009; Fombonne, 2001; Fombonne 2003).  Although there has been at lot of advances in the understanding of causes of autism, there are still at lot of gaps that remain.  It has been postulated that many genetic factors, as well as environmental factors, account for the most cases of ASD.

The publication of Gerber and Offit

According to Baker (2008), in late 1990s controversies regarding the relation between MMR vaccines and diagnosis of ASDs began to arise when parent and guardians of children with ASD, as well as autism action groups, began claiming that thimerosal, a preservative once contained in MMR vaccines, was causally associated with their children autism.  Furthermore, public opinion was further exacerbated by the Wakefield, Murch and Anthony (1998) publication in The Lancet where it was claimed that MMR vaccines resulted in intestinal inflammation that caused translocation of non-permeable peptides to the bloodstream and the brain, where they affected the development.  Since dissemination of that publication, many parents have been reluctant to accept MMR vaccines for their children in both the United States and United Kingdom (Baker, 2008).  As a result, MMR vaccination rates have decreased in the United States and According to Gerber and Offit (2009), several issues undermined the review by Wakefield, Murch and Anthony (1998) publication of these case series.  Firstly, the self-referred cohort did not contain control subjects that precluded authors from determining if the occurrence of autism by the receipt of MMR vaccine was coincidental or causal.  Almost 50,000 British kids have received MMR vaccine per month between the age of 1 and 2, at times when autism normally presents, coincidental associations were unavoidable.  Secondly, neuropsychological or endoscopic assessments were not blind, and data were not gathered completely or systematically.  Thirdly, gastrointestinal symptoms in several children did not predate autism, which is quite inconsistent with the fact that intestinal inflammation facilitated blood stream invasion.  Fourthly, MMR has not been found to result in loss of intestinal barrier or chronic intestinal inflammation.  The recent study by Hornig et al. (2008) shown that mumps, measles or rubella virus genomes were not detected in children with or without autism.  Fifthly, putative encephalopathic peptides moving from intestines to the brain were not identified.

Effect of MMR vaccination on children's health

Thimerosal has been used as preservative (antibacterial) in multi dose vaccine preparations for more than 50 years.  Thimerosal is approximately 50% ethylmercury by weight, and it is not contained in live virus vaccines, such as MMR.  In 1999, the US and Food and Drug Administration found that “children might be receiving as much as 187.5 microgram of mercury within the first six months of life” (Gerber and Offit, 2008).   Even thought there was no scientific data or evidence that ethylmercury contained in vaccines causes harm, in 1999 the American Academy of pediatrics and the Public Health Service recommended the immediate removal of mercury from all vaccines given to young infants as a precautionary measure. “The signs and symptoms of mercury poisoning are clearly distinct from those of autism, concerns about mercury as a cause of autism, similar to those of MMR vaccine-biologically implausible; children with mercury poisoning show characteristic motor, speech, sensory, psychiatry, visual and head circumference changes that are either fundamentally different from those if or absent in children with autism” (Gerber and Offit, 2008)

Cook, et al (2010) stated that “due to the nature of MMR vaccinations, randomized controlled trial (RCTs) of the effects of MMR vaccine on diagnosis of ASDs is ethically unfeasible”. Furthermore, the study of Schechter and Grether in this issue of the Archieve provides evidence of the lack of association between the Thimerosal exposure and the risk of autism in the US.  Using an ecologic design, authors showed that the prevalence rate of autism has been increasing continuously during the study period, even after discontinuation of thimerosal.  “If there been any risk association between thimerosal containing vaccine and autism, the rate of autism should have decreased in young children between 2004 and 2007.  Instead, the rate did not attenuate, indicating that thimerosal exposure bears no relationship to the risk of autism” (Fombonne, 2008).

Many parents of children with ASD believe that vaccines contributed to ASD and “half either change or discontinue vaccinations, indicating the potential for a subset of under-vaccinated and at-risk children.  Given that any link between vaccines and autism has been refuted, this indicates a lengthy delay in the translation of science to practice and public knowledge”   (Bazzano et al. 2012). 

Autism has been a disease that has existed in people’s lives for a long time, though not much attention has been channeled into it. This research’s objective was to raise issues regarding autism, its prevalence, how parents with kids suffering from autism are affected, as well as vaccines that are available for ASDs patients. The approach used in this research to tackle the problem was a distinctive analysis of secondary resources and critically analyzing findings in these resources.

Two years after the publication of the Wakefield et al 1998 study, reviews completed by the Institute of Medicine (IOM), the American Academy of Pediatrics and the United Kingdom Medical Research Council gave a conclusion that there was no statistical association between MMR vaccinations and incidence rates of ASDs.  IOM conducted a review of all available evidence (completed studies, ongoing studies, published medical and scientific papers and expert testimonies) related to this supposed association and found no consistent link between MMR vaccinations and diagnosis of ASDs.  Hobson et al (2012) in his meta-analysis concluded that due to very nature of MMR vaccinations, randomized control trials (RCTs) of effects of MMR vaccines on the diagnosis of ASD are unfeasible ethically (Cook et al.  2010).   Even so, odds of ASD attributable to receiving an MMR vaccination are not statistically equivalent; odds of ASD diagnosis are, however, substantially smaller for those receiving an MMR vaccination than for those who not.

Conclusion

Parents of autistic children need to be educated and reassured that autism in their child did not occur as a result of the MMR vaccine.  “Discussion about vaccinations should be emphasized and specifically tailored to meet the needs of parents of children with autism/ASD” (Bazzano et al. 2012).   It is crucial that pediatricians provide educational tools and research data to parents of autistic children who are concerned about immunizations and the risk of autism.  Children should be normally vaccinated to prevent diseases that can be preventable through immunization.  Bazzano et al. (2012), suggest that “further research should focus on assessing national vaccination coverage rates in children with ASD and how best to communicated with parents of children with autism/ASD about vaccinations.

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