Cristopher E.

Caez Leslie Wolcott ENC 1102-0038 March 14, 2014 Autism and Vaccines: The Argument Heard Around the World Ever since 1998 when Dr. Wakefield first introduced the idea that the measles, mumps, and rubella (MMR) vaccine had a direct relation to a child developing autism, many have accepted and opposed this idea with little or conclusive evidence on the subject. Autism is a very wide disorder and can range from being very mild to extremely debilitating for a child and the family, certainly a condition no one would like to be afflicted with. The debate has since sparked up and down throughout time; people accepting the fact that not only the MMR vaccine, but also the thought that all vaccines cause autism with little evidence to back it up other than hearing someone else say it. In this bibliography we will discuss both sides of the debate, information that has both been accepted and rejected by the scientific community based on it methods, results, and conclusion. This bibliography will present the facts of each source, stating what they said and how it is relevant to the current discussion. It will take a look at flaws of the original study, the possible agenda behind it, what it presented the world with, and how it has affected parents decisions to vaccinate their children. It will also take a look at the differences in children with autism with children with normal development and children with other debilitating disorders and the difference it

makes when looking at the big picture. Finally we will take a look at how children with autism have similar symptoms when it comes to their gastrointestinal system and how diet affects the childs development through time. This bibliography is aimed specifically at parents, focusing on giving them the information they need to make a decision to vaccinate or not vaccinate their children. The information contained here could make the difference between your childs safety the those around the child, since we live in a world full of various diseases, many of which are preventable with proper vaccination and prevention. Read with an open mind and look at the information presented as all of it has been critically reviewed and edited to have the most up to date and accurate information possible. Bedford, H. E., & Elliman, D. A. (2010, February 6). MMR vaccine and autism. BMJ: British Medical Journal (Overseas & Retired Doctors Edition). pp. 271-272. doi:10.1136/bmj.c655. This editorial focuses on the problems that arose after Wakefield conducted his research and the media started spreading the scientific results. Wakefields study found that the MMR vaccine caused a new form of regressive autism that had a major impact on the childs health (Wakefield et al.). However, this wasnt what turned the medias intere st, it was the fact that one of the authors of the paper (Wakefield) had suggested that instead of giving a vaccine that contained measles, mumps, and rubella that they give the vaccines separately. This was not supported by scientific evidence and it was based purely on bias, but it

was also found that Wakefield had been contracted by a solicitor to help launch a lawsuit against the MMR vaccine manufacturers (Deer 839). Soon the news flew around the world and parents everywhere became concerned as to what to do in regards to getting the MMR vaccination for their child and it wasnt until celebrities started putting in their input on how they would not vaccinate their children that vaccination rates went down significantly. Between 1995-6 the MMR vaccine had a 92% acceptance rate, before Wakefields paper had been published in 1998. Since after the publication the acceptance rate of the MMR vaccine fell to 80% in the 2003-4 years and was found to have gone up to 86.5% acceptance rate in 2009. The misinformation, bias, and parent confusion on the subject led to many not vaccinating their children and putting them and those around them at risk. Deer, B. (0001). Wakefield's autistic enterocolitis under the microscope (English). BMJ. British Medical Journal (International Ed.), 340(7751), 838-841. The journal entry by Brian Deer focuses on the flaws that led to Wakefields paper being published in the first place. It wasnt the faulty science, or the method used but rather the lack of review. At first pathologists were not convinced by Wakefields research, and decided to pass it on to an expert histopathologist that worked in the Royal Free Hospital. He was to analyze the biopsies obtained by the 12 children, 11 of which gave a supposed clear diagnosis of a regressive form of autism (Wakefield et al.). But somehow it fell through the cracks, no one past

Wakefield, who is not a pathologist of any kind and cannot fully diagnose biopsies on a professional level like a certified pathologist can, determined the results of the childrens biopsies. All this leading to the paper being published and causing so much controversy that eventually upon review and various researchers trying to recreate Wakefields results, let to the paper being retracted and all it data supposedly gone forever and has yet to be found again. D'Eufemia, P., Celli, M., Finocchiaro, R., Pacifico, L., Viozzi, L., Zaccagnini, M., & ... Giardini, O. (1996). Abnormal intestinal permeability in children with autism. Acta Paediatrica (Oslo, Norway: 1992), 85(9), 1076-1079. In this study 21 autistic children and 40 children with normal development were compared in reference to their gastrointestinal symptoms. All children were subject to endoscopies and biopsies to see if there was any difference in autistic children from children with normal development. The study determined that children who suffered autism were more likely to have damage in their intestines resulting from the intestines own mucous lining, making the intestine more sensitive; this result was found in 9 of the 21 autistic children and not at all in the control group. Mannitol injections were given to these children to take the majority of the salinity and water out of the mucous membrane in the intestines to reduce irritation; these children showed significant recovery (DEufemia et al.). It was determined that the cause of the intestinal sensitivity could be caused by the foods the child is eating, causing the mucous membranes in the intestines to

become harmful to its lining further causing behavioral abnormalities in the child. Elder, J., Shankar, M., Shuster, J., Theriaque, D., Burns, S., & Sherrill, L. (0001). The gluten-free, casein-free diet in autism : Results of a preliminary double blind clinical trial (English). Journal Of Autism And Developmental Disorders, 36(3), 413-420. The study included 15 children between the ages of 2-16 years of age all with autism spectrum disorder (ASD), for 12 weeks they were exposed to either a gluten-free, or a casein-free diet as a form of treatment for the patients gastrointestinal problems. To make sure that there would be no conflicting interests or bias, both the patients and the lead researcher had no idea which diet each patient had received until the end of the study (Elder et al. 415). Upon review, the parents of 7 children came forth and reported that their child experienced improvements in language, decreased hyperactivity, and decrease in tantrums as well as gastrointestinal symptoms. The parents did not know which diet their child was on but 9 childrens parents decided to keep the diet (Elder et al. 418). When asked which diet the parents thought their child was on for the 12 weeks 5 guessed correctly, 2 were unsure, and 6 were wrong. Fombonne, E., & Chakrabarti, S. (2001). No evidence for a new variant of measles-mumps-rubella-induced autism. Pediatrics, 108(4), E58. This study analyzed three samples of children who were born between 1992 and 1995 who were diagnosed with developmental disorders in the

UK. Comparing the date of these children with two clinical trials that had been done previously (1 pre-MMR and 1 post-MMR) with those autistic patients (Fombonne et al.). The time at which these children received the MMR vaccine (13.5 months) was kept the same for all and the time in months are which parents developed concerns for their childs condition were also taken into account. All this information was obtained through medical records and computer recorded data. The results showered that only a small number of children had worsening conditions in relation to development (about 0.6 out of 10 000 children) and the regressive developmental disorders were not related to the MMR vaccine in any way. A cross examination of children who received the vaccine and those who did not showed no change in the number of children diagnosed with those regressive disorders. Fombonne, E., & Cook, E. (2003). MMR and autistic enterocolitis: consistent epidemiological failure to find an association. Molecular Psychiatry, 8(2), 133-134. This commentary discusses Wakefields study along with another study conducted in 1988 with a larger sample to try and confirm an association between the MMR vaccine and autism. In 1998 Wakefield conducted his study and claimed that the MMR vaccine cause what he called autistic enterocolitis, or an inflammation in the intestines that was and indicator of the development of autism in children after receiving the MMR vaccination (Wakefield et al.). Since then many studies have not only failed to

conclusively link autism to the MMR vaccine, but are unable to completely replicate Wakefields results (Fombonne, Cook 133). In 2002 a study with a sample of 473 children who had all received the MMR vaccine was conducted; it was found that 17% had some sort of gastrointestinal issues, and 25% showed a regression or loss of skill or development along with the gastrointestinal issues. Through this study it was determined that there is an association between regression and bowel symptoms (Taylor et al.), but still failure to associate the MMR vaccine to the development of autism. The major strength in this 2002 study was the fact that it included a large sample size, had very good controls, had a 20-year interval for gathering of information, and thorough record keeping of immunization completely unlike Wakefields study. Galiatsatos, P., Gologan, A., & Lamoureux, E. (2009). Autistic enterocolitis: fact or fiction?. Canadian Journal Of Gastroenterology = Journal Canadien De Gastroenterologie, 23(2), 95-98. This academic paper starts with two case studies followed by a discussion on the topic of autism, addressing both the argument of a link between it and the MMR vaccine, and autism in general as a condition. In the first case study we are introduced to an 18 year old male who grew up in a rural area and works on a farm; 5 years prior to the consultation, after being subjected to a gastroscopy he was diagnosed with mild nonspecific gastritis or a minor inflammation of the intestines, upon receiving steroids the patient improved. It was determined that had the patient lived in an

urban area as a child, he would have been diagnosed with autism (Galiatsatos et al. 95). In the second case study we are introduced to a 19-year-old female with a long history of intestinal problems and a recent diagnosis of Aspergers, now currently known as high-functioning autism (APA). Her gastroscopy showed multiple lesions and erosions in the intestinal lining, biopsies were taken and found to be normal. A change of diet was sufficient enough to lessen the intestinal issues the patient was facing (Galiatsatos et al. 96). The purpose of these two case studies was to show that there is in fact a relation between intestinal issues and autism, again quoting that 70% of autistic children have some from of bowel problem or condition (Valicenti-McDermott et al.). When Wakefield originally conducted his study, he used a small sample size, 12 children, 9 of whom were already diagnosed as autistic and had gastrointestinal problems, which Wakefield termed nonspecific colitis (Wakefield et al.). A study conducted with 36 autistic children complaining of different gastrointestinal symptoms found that 64.4% had inflammation of the esophagus, 41.7% had inflammation of the intestines, and 66.7% had inflammation in the lower large intestine near the anus (Horvath et al.); this further proves the relationship between gastrointestinal conditions and autism but does not prove that one is an indicator or a cause of the other. Finally it was noted that changes in diet such as a gluten or casein-free diets improved gastrointestinal conditions in children with autism (Elder et al.).

Horvath, K., Papadimitriou, J., Rabsztyn, A., Dranchenberg, C., & TIildon, J. (0001). Gastrointestinal abnormalities in children with autistic disorder (English). The Journal Of Pediatrics, 135(5), 559-563. In this study 36 children (mean age 5.7) diagnosed with autistic disorder underwent gastrointestinal biopsies and endoscopies to see the cause of many of the childrens gastrointestinal problems. The most common symptoms were diarrhea, gas, abdominal discomfort, and abdominal distension (bloating). Upon review of the results of the tests it was found that 69.4% of the children had grade I or II reflux esophagitis (commonly known as GERD), 41.7% had chronic inflammation in the intestines, and 66.7% had chronic inflammation of the lower large intestine (Horvath et al.). When undiagnosed these gastrointestinal disorders can contribute to behavioral problems or changes in non-verbal autistic children, making it seem like the autism is regressing, when in fact the child is experiencing mild to severe discomfort and does not know how to express it. Further studies have yet to determine the possible association between the brain and gastrointestinal issues in children with autism disorder(s). MacDonald, T., Domizio, P., & Wakefield, A. (0001). Autistic enterocolitis; is it a histopathological entity? Commentary (English). Histopathology, 50(3), 371-384. This paper is a commentary of various studies claiming to have found a link, or evidence of a link between the MMR vaccine and autism. MacDonald starts by stating he and the team went over 9 different

research journals and articles on the subject, all of which had been published within the last ten years. The first criticism of the work was that the first seven papers written on the subject came from one source, Wakefield himself and were all written in a similar manner. Wakefields first study, claiming that the MMR vaccine caused children to develop a form of autism he termed autistic enterocolitis (Wakefield et al. 637-641) is faulty both in the sample size used and in its conclusion. Wakefield took 12 children, 9 of which had already been diagnosed with autism and exposed them to the MMR vaccine. Afterwards biopsies of the children were examined and determined to have an inflammation related to a new string of autism, autistic enterocolits. Many autistic children already show symptoms of bowel disordes/diseases and the study at best suggests that there may bee some changes in the colon of children with regressive autism (MacDonald et al. 373), which needs to be studied by itself further before jumping to further conclusions. Another study concluded that several biopsies of children with regressive autism showed inflammation consistent with Wakefields findings (Furlano et al. 366-372). This study was criticized because of its methods, the paper did not describe the method of study adequately and the controls used varied and did not apply to every child. Multiple studies and multiple control groups were needed to determine a definitive answer (MacDonald et al.). Many of the other papers discussed in this commentary also show the same issues, lack of data, improper methods, sample size, and improper controls.

Taylor, B., Miller, E., Lingam, R., Andrews, N., Simmons, A., & Stowe, J. (n.d). Measles, mumps, and rubella vaccination and bowel problems or developmental regression in children with autism: Population study. Bmj, 324(7334), 393-396. Taylor et al. set out to prove that the form of autism that Wakefield had declared new was in fact already known and titled as atypical autism and was not in fact related to the MMR vaccine. The study took 278 children with childhood autism and 195 with atypical autism; of all these children 17% had some sort of bowel problem (diarrhea, food allergy, constipation etc.). The children diagnosed with atypical autism also showed similar results, 18% of them showing symptoms of some sort of bowel problem(s) (Taylor et al.). Of all the children, 25% showed signs of regression, loss of speech and change in behavior being the most common recorded which was yet again prominent in children with atypical autism. No trends or changes in percentages were found in children exposed to the MMR vaccine after it was launched in 1998. This showed how Wakefields new strand of autistic enterolocits was not indeed plausible as another form of autism showed regression in relation to bowel symptoms without the exposure of the MMR vaccine and how percentages did not change post the introduction of the MMR vaccine. (Taylor et al.). Valicenti-McDermott, M., McVicar, K., Rapin, I., Wershil, B. K., Cohen, H., & Shinnar, S. (2006). Frequency of Gastrointestinal Symptoms in Children with Autistic Spectrum Disorders and Association with Family History of

Autoimmune Disease. Journal Of Developmental And Behavioral Pediatrics, 27(Suppl2), S128-S137. doi:10.1097/00004703-20060400200011 50 children with autistic spectrum disorder (ASD), 50 children with normal development, and 50 children with other developmental disorders (DD) were gathered to study their gastrointestinal symptoms. 74% of the children were boys with a mean age of 7.6 years and it was found that 70% of children with ASD showed some form of gastrointestinal issues compared to 28% of children with normal development and 42% of children with DD (Valicenti-McDermott et al.). It was also found that children with ASD were more picky eaters (60%) than children with normal development (22%) and children with DD (36%). Gastrointestinal symptoms were found to be associated with children who had ASD; family history did not play a role in the child developing gastrointestinal symptoms. Wright, N. (2010). Does autistic enterocolitis exist?. BMJ (Clinical Research Ed.), 340c1807. doi:10.1136/bmj.c1807. This editorial published in a UK research journal looks at Wakefields original study involving the discovery of a link between autism and the MMR vaccine and points out various flaws and holes in the research that ultimately led the research paper to be repealed. The first of these concerns was by which means the term colitis more commonly known as the inflammation of the colon or large intestine was being applied, as the

term colitis deals with a large variety of gastrointestinal conditions and diseases (Wright 819). The second major flaw pointed out was in the staff involved in the study, there seemed to be no pathologist to diagnose the biopsies that were taken from the sample of 12 children, and upon review by a pathologist later on no abnormalities were found. The third and lastly major flaw in Wakefields research is the automatic conclusion that relation means causation or that two events that occur together concludes to one being the result of the other; 70% of autistic children already have some form of a bowel condition (Valicenti-McDermott et al.) such as constipation, diarrhea, etc., but this does not confirm the fact that any bowel condition or problem will lead to autism as a result. Lack of evidence and data leave the research to be inconclusive in giving a definitive answer, time may be the only way to receive a final concrete answer.