Measles, mumps, and rubella vaccination and bowel problems or developmental regression in children with autism: population study.
TL;DR: Findings provide no support for an MMR associated “new variant” form of autism with developmental regression and bowel problems, and further evidence against involvement of MMR vaccine in the initiation of autism.
Abstract: Objectives: To investigate whether measles, mumps, and rubella (MMR) vaccination is associated with bowel problems and developmental regression in children with autism, looking for evidence of a “new variant” form of autism. Design: Population study with case note review linked to independently recorded vaccine data. Setting: Five health districts in north east London. Participants: 278 children with core autism and 195 with atypical autism, mainly identified from computerised disability registers and born between 1979 and 1998. Main outcome measures: Recorded bowel problems lasting at least three months, age of reported regression of the child9s development where it was a feature, and relation of these to MMR vaccination. Results: The proportion of children with developmental regression (25% overall) or bowel symptoms (17%) did not change significantly (P value for trend 0.50 and 0.47, respectively) during the 20 years from 1979, a period which included the introduction of MMR vaccination in October 1988. No significant difference was found in rates of bowel problems or regression in children who received the MMR vaccine before their parents became concerned about their development (where MMR might have caused or triggered the autism with regression or bowel problem), compared with those who received it only after such concern and those who had not received the MMR vaccine. A possible association between non-specific bowel problems and regression in children with autism was seen but this was unrelated to MMR vaccination. Conclusions: These findings provide no support for an MMR associated “new variant” form of autism with developmental regression and bowel problems, and further evidence against involvement of MMR vaccine in the initiation of autism. What is already known on this topic A “new variant” form of autism has been hypothesised, associated with developmental regression and bowel problems and caused or triggered by the MMR vaccination This postulated association along with media attention has had a major adverse effect on public confidence in the vaccine Although population studies have shown no association between autism and MMR vaccine it has been further postulated that various environmental or genetic cofactors are required for the effect What this study adds The proportion of children with autism who had developmental regression or bowel problems has not changed over the 20 years from 1979 Neither developmental regression nor bowel problems in children with autism was associated with MMR vaccination No evidence was found for a “new variant” form of autism
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TL;DR: Important issues, such as management of associated medical problems, pharmacologic and nonpharmacologic intervention for challenging behaviors or coexisting mental health conditions, and use of complementary and alternative medical treatments, are also addressed.
Abstract: Pediatricians have an important role not only in early recognition and evaluation of autism spectrum disorders but also in chronic management of these disorders. The primary goals of treatment are to maximize the child's ultimate functional independence and quality of life by minimizing the core autism spectrum disorder features, facilitating development and learning, promoting socialization, reducing maladaptive behaviors, and educating and supporting families. To assist pediatricians in educating families and guiding them toward empirically supported interventions for their children, this report reviews the educational strategies and associated therapies that are the primary treatments for children with autism spectrum disorders. Optimization of health care is likely to have a positive effect on habilitative progress, functional outcome, and quality of life; therefore, important issues, such as management of associated medical problems, pharmacologic and nonpharmacologic intervention for challenging behaviors or coexisting mental health conditions, and use of complementary and alternative medical treatments, are also addressed.
1,010 citations
TL;DR: The findings of a survey that found a rate of 34 per 10000 for autism spectrum disorders (ASDs) among 3to 10-year-old children in metropolitan Atlanta suggest that these differences might reflect new diagnostic criteria for autism and increased availability of developmental disability services for children with autism in the 1990s.
Abstract: THE NUMBER OF EPIDEMIOLOGICAL STUDIES OF AUtism has increased in recent years, including in the United States, where investigators are now catching up in what has traditionally been a weak area of child psychiatric research in North America. In this issue of THE JOURNAL, Yeargin-Allsopp et al report the findings of a survey, which was funded by the Centers for Disease Control and Prevention, that found a rate of 34 per 10000 for autism spectrum disorders (ASDs) among 3to 10-year-old children in metropolitan Atlanta. The strengths of the survey include use of multiple ascertainment sources and large sample size (ie, 987 confirmed ASD cases compared with a median sample size of 50 in 32 previous studies), thereby allowing the authors to have good precision in the estimates and to conduct meaningful subgroup analyses. In addition, this study is the first to derive a robust population-based estimate for the rate of ASD in black children, which is comparable to other racial groups. Other findings are typical of those found in previous surveys with ASD cases, with a strong overrepresentation of boys, cognitive impairments in more than two thirds of cases, and a relatively high rate (8%) of epilepsy. Approximately 18% of the sample did not have a previous diagnosis or were not suspected of having ASD, and children from black, younger, or less educated mothers were more often identified through schools as the only source of case finding. These findings highlight the need to rely on multiple ascertainment sources in epidemiological studies of ASD and caution against findings that are based on single service provider databases. The prevalence rate of 34 per 10000 is, however, likely to be an underestimate. First, as the authors point out, children with milder or high-functioning (ie, normal IQ) ASD subtypes are likely to have been missed. Second, the lower prevalence in 3and 4-year-olds may reflect lower sensitivity of case identification among younger children for developmental disorders that often are diagnosed later. Third, there was an unexpected decrease in prevalence among 9and 10-year-olds. Although it would be tempting to interpret this age trend as indicative of a secular increase in the rate of ASD (ie, the younger the birth cohort, the higher the prevalence), such an explanation is both unlikely and biologically implausible because rates plateaued for birth cohorts aged 5 through 8. Rather, the authors suggest that these differences might reflect new diagnostic criteria for autism and increased availability of developmental disability services for children with autism in the 1990s. What this means, however, is that the rate of 41 to 45 in 10000 obtained for the 5to 8-year-olds might be more accurate. This rate also is more in line with those of 3 recent surveys that yielded prevalence estimates in the range of 60 per 10000. High prevalence rates from more recent epidemiological surveys have fueled the debate about a possible epidemic of autism. However, 4 separate issues need to be addressed. The first issue concerns the best current estimate for the prevalence of autism and related disorders. Increasing and consistent evidence from recent surveys shows that the prevalence rate for ASDs (including not only autism disorder but also Asperger disorder and pervasive developmental disorder–not otherwise specified) is approximately 60 per 10000; the study results from Yeargin-Allsopp et al concur with this conclusion. This estimate translates to approximately 425000 children younger than age 18 years with ASDs in the United States, including 114000 children younger than 5 years. The second issue is whether the prevalence of ASD has increased over time. Surveys conducted in the 1960s and 1970s only dealt with autism disorder (as opposed to ASD) and with a rather narrow definition of autism, as per Kanner’s descriptions, and not accounting for autism occurring in subjects who are not mentally retarded. Thus, comparisons of rates over time generally deal with studies that have used different case definitions, making interpretation of time trends difficult. The closest estimate of ASD prevalence available in the late 1970s was 20 per 10000 in a survey from the United Kingdom that was limited to the severely impaired children with ASD. Comparing rates for subtypes of ASD provide another avenue for estimation over time especially for autism disorder, but as shown by Yeargin-Allsopp et al and other surveys, the breakdown in ASD subtypes is not always reli-
718 citations
TL;DR: It is shown that a formal game theoretical analysis of the problem of whether a sufficient proportion of the population is already immune, either naturally or by vaccination, leads to new insights that help to explain human decision-making with respect to vaccination.
Abstract: Voluntary vaccination policies for childhood diseases present parents with a subtle challenge: if a sufficient proportion of the population is already immune, either naturally or by vaccination, then even the slightest risk associated with vaccination will outweigh the risk from infection. As a result, individual self-interest might preclude complete eradication of a vaccine-preventable disease. We show that a formal game theoretical analysis of this problem leads to new insights that help to explain human decision-making with respect to vaccination. Increases in perceived vaccine risk will tend to induce larger declines in vaccine uptake for pathogens that cause more secondary infections (such as measles and pertussis). After a vaccine scare, even if perceived vaccine risk is greatly reduced, it will be relatively difficult to restore prescare vaccine coverage levels.
704 citations
Harvard University1, University of Southern California2, University of Arkansas for Medical Sciences3, University of Colorado Denver4, Boston Children's Hospital5, New York University6, University of California, Davis7, Columbia University Medical Center8, Baylor College of Medicine9, State University of New York System10, Columbia University11, University of Rochester Medical Center12, Mahidol University13, University of Medicine and Dentistry of New Jersey14, Cleveland Clinic15, New York Academy of Medicine16, Children's Memorial Hospital17, University of California, Los Angeles18
TL;DR: The consensus expert opinion of the panel was that individuals with ASDs deserve the same thoroughness and standard of care in the diagnostic workup and treatment of gastrointestinal concerns as should occur for patients without ASDs.
Abstract: Autism spectrum disorders (ASDs) are common and clinically heterogeneous neurodevelopmental disorders. Gastrointestinal disorders and associated symptoms are commonly reported in individuals with ASDs, but key issues such as the prevalence and best treatment of these conditions are incompletely understood. A central difficulty in recognizing and characterizing gastrointestinal dysfunction with ASDs is the communication difficulties experienced by many affected individuals. A multidisciplinary panel reviewed the medical literature with the aim of generating evidence-based recommendations for diagnostic evaluation and management of gastrointestinal problems in this patient population. The panel concluded that evidence-based recommendations are not yet available. The consensus expert opinion of the panel was that individuals with ASDs deserve the same thoroughness and standard of care in the diagnostic workup and treatment of gastrointestinal concerns as should occur for patients without ASDs. Care providers should be aware that problem behavior in patients with ASDs may be the primary or sole symptom of the underlying medical condition, including some gastrointestinal disorders. For these patients, integration of behavioral and medical care may be most beneficial. Priorities for future research are identified to advance our understanding and management of gastrointestinal disorders in persons with ASDs.
682 citations
TL;DR: Determinants of parental decision-making about vaccination are looked at and an overview of the history of anti-vaccination movements and its clinical impact is provided.
Abstract: Despite being recognized as one of the most successful public health measures, vaccination is perceived as unsafe and unnecessary by a growing number of parents. Anti-vaccination movements have been implicated in lowered vaccine acceptance rates and in the increase in vaccine-preventable disease outbreaks and epidemics. In this review, we will look at determinants of parental decision-making about vaccination and provide an overview of the history of anti-vaccination movements and its clinical impact.
612 citations
References
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TL;DR: The revised interview has been reorganized, shortened, modified to be appropriate for children with mental ages from about 18 months into adulthood and linked to ICD-10 and DSM-IV criteria.
Abstract: Describes the Autism Diagnostic Interview-Revised (ADI-R), a revision of the Autism Diagnostic Interview, a semistructured, investigator-based interview for caregivers of children and adults for whom autism or pervasive developmental disorders is a possible diagnosis. The revised interview has been reorganized, shortened, modified to be appropriate for children with mental ages from about 18 months into adulthood and linked to ICD-10 and DSM-IV criteria. Psychometric data are presented for a sample of preschool children.
8,264 citations
TL;DR: In this paper, the authors investigated a consecutive series of children with chronic enterocolitis and regressive developmental disorder, and identified associated gastrointestinal disease and developmental regression in a group of previously normal children, which was generally associated in time with possible environmental triggers.
2,505 citations
1,125 citations
TL;DR: The Wisconsin CF Neonatal Screening Project as discussed by the authors was designed as a randomized clinical trial to assess the benefits and risks of early diagnosis through screening, and the validity of the randomization method assessed by comparing 16 demographic variables.
Abstract: Objective. Despite its relative frequency among autosomal recessive diseases and the availability of the sweat test, cystic fibrosis (CF) has been difficult to diagnose in early childhood, and delays can lead to severe malnutrition, lung disease, or even death. The Wisconsin CF Neonatal Screening Project was designed as a randomized clinical trial to assess the benefits and risks of early diagnosis through screening. In addition, the incidence of CF was determined, and the validity of our randomization method assessed by comparing 16 demographic variables. Methodology. Immunoreactive trypsinogen analysis was applied to dried newborn blood specimens for recognition of CF risk from 1985 to 1991 and was coupled to DNA-based detection of the ΔF508 mutation from 1991 to 1994. Randomization of 650 341 newborns occurred when their blood specimens reached the Wisconsin screening laboratory. This created 2 groups—an early diagnosis, screened cohort and a standard diagnosis or control group. To avoid selection bias, we devised a unique unblinding method with a surveillance program to completely identify the control subjects. Because sequential analysis of nutritional outcome measures revealed significantly better growth in screened patients during 1996, we accelerated the unblinding and completely identified the control group by April 1998. Having each member of this cohort enrolled and evaluated for at least 1 year and having completed a comprehensive surveillance program, we performed another statistical analysis of anthropometric evaluated indices that includes all CF patients without meconium ileus. Results. The incidence of classical CF, ie, patients diagnosed in this trial with a sweat chloride of 60 mEq/L greater, was 1:4189. By incorporating other CF patients born during the randomization period, including 2 autopsy diagnosed patients and 8 probable patients, we calculate a maximum incidence of 1:3938 (95% confidence interval: 3402–4611). Although there were group differences in the proportion of patients with ΔF508 genotypes and with pancreatic insufficiency, validity of the randomization plan was demonstrated by analyzing 16 demographic variables and finding no significant difference after adjustment for multiple comparisons. Focusing on patients without meconium ileus, we found a marked difference in the mean ± standard deviation age of diagnosis for screened patients (13 ± 37 weeks), compared with the standard diagnosis group (100 ± 117). Anthropometric indices of nutritional status were significantly higher at diagnosis in the screened group, including length/height, weight, and head circumference. During 13 years of study, despite similar nutritional therapy and the inherently better pancreatic status of the control group, analysis of nutritional outcomes revealed significantly greater growth associated with early diagnosis. Most impressively, the screened group had a much lower proportion of patients with weight and height data below the 10th percentile throughout childhood. Conclusions. Although the screened group had a higher proportion of patients with pancreatic insufficiency, their growth indices were significantly better than those of the control group during the 13-year follow-up evaluation and, therefore, this randomized clinical trial of early CF diagnosis must be interpreted as unequivocally positive. Our conclusions did not change when the height and weight data before 4 years of age for the controls detected by unblinding were included in the analysis. Also, comparison of growth outcomes after 4 years of age in all subjects showed persistence of the significant differences. Therefore, selection bias has been eliminated as a potential explanation. In addition, the results show that severe malnutrition persists after delayed diagnosis of CF and that catch-up may not be possible. We conclude that early diagnosis of CF through neonatal screening combined with aggressive nutritional therapy can result in significantly enhanced long-term nutritional status.
766 citations
TL;DR: The authors' analyses do not support a causal association between MMR vaccine and autism, and it is suggested that if such an association occurs, it is so rare that it could not be identified in this large regional sample.
722 citations