scispace - formally typeset
Search or ask a question
Journal ArticleDOI

Autism and measles, mumps, and rubella vaccine: no epidemiological evidence for a causal association

12 Jun 1999-The Lancet (Elsevier)-Vol. 353, Iss: 9169, pp 2026-2029
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.
About: This article is published in The Lancet.The article was published on 1999-06-12 and is currently open access. It has received 722 citations till now. The article focuses on the topics: Regressive autism & Autism.

Summary (2 min read)

Introduction

  • The postulated causal link between MMR vaccination and autism was based on a reported close temporal association between these two events.
  • Since MMR vaccine is given at around 12–15 months of age and the mean age at which parents of children with autism first report concern about their child’s development is 18–19 months,5 a close temporal association in some autistic children would be expected by chance.
  • The authors used caseseries analysis methods to test for clustering of onsets within defined postvaccination periods.

Patients and methods

  • Children with autistic disorders born since 1979 were identified in eight health districts in mid-1998 from computerised special needs/disability registers at child development centres and from records in special schools.
  • By use of criteria of the International Classification of Diseases, tenth revision (ICD10), the diagnosis of autism was checked against information in the available records on the child’s present condition and his or her condition between the ages of 18 months and 3 years.
  • Inter-rater reliability was tested on 20 case records (independent completion of the data-collection form); the concordance was above 95%.
  • First, trends in the time series of cases were analysed by Poisson regression.
  • To circumvent this problem, only cases aged 0–59 months at diagnosis and born in the years 1979–92 were included in this analysis.

Results

  • The median ages at diagnosis, first parental concern, and regression according to diagnostic category are shown in table 1.
  • Regression was recorded for 29% of core autism cases compared with 18% of atypical cases and 6% of those with Asperger’s syndrome.
  • For the core and atypical cases, there was no evidence of a sudden “step-up” in 1987, the first birth cohorts eligible for MMR vaccine in the second year of life (p>0·25).
  • Neither was there evidence that the exponential trend changed after 1987 .

Variable Core autism Atypical Asperger’s

  • The results of the case-series analyses are shown in table 2; the results were similar when the analysis was restricted to cases confirmed by ICD10 criteria.
  • There was no significant clustering of interval to diagnosis or regression within the time periods defined.
  • When the data were reanalysed without cases with recorded age at parental concern of 18 months (n=61), all statistical significance disappeared.

Discussion

  • Vaccination and vaccine safety are issues of major concern to the public, their elected representatives, and all health-care workers.
  • Possible adverse reactions to vaccines have a particular attraction to various pressure groups and to the media, with important, and possibly catastrophic, effects on public confidence in immunisations and on vaccine uptake.
  • The study has some limitations: two of these are that the authors could not verify the diagnosis according to ICD10 criteria in some cases, and that the ascertainment may have been incomplete.
  • There is uncertainty about whether the prevalence of autism is increasing.
  • The authors looked for evidence of a possible causal association between MMR vaccination and onset of autism by investigating whether, after adjustment for birth-cohort effects on incidence, age at diagnosis of autism varied with vaccination status.

Autism diagnosis (n=357)

  • Core and atypical cases vaccinated by the end of the second year of life was similar to that in the same birth cohorts in the North East Thames region.
  • For age at first parental concern, no significant temporal clustering was seen for cases of core autism or atypical autism, with the exception of a single interval within 6 months of MMR vaccine associated with a peak in reported age at first parental concern at 18 months.
  • The authors results do not support the hypothesis that MMR vaccination is causally related to autism, either its initiation or to the onset of regression—the main symptom mentioned in the paper by Wakefield and others.
  • The two datasets were collected independently of each other, so avoiding the bias that can occur when cases are ascertained as a result of a perceived link with vaccination.
  • This study does not rule out the possibility of a rare idiosyncratic response to MMR.

Contributors

  • Brent Taylor, Elizabeth Miller, Christina Petropoulos, and Jun Li were responsible for study design.
  • Brent Taylor, Christina Petropoulos, and Isabelle Favot-Mayaud were responsible for case identification and ascertainment.
  • Elizabeth Miller, Pauline Waight, Jun Li, Isabelle Favot-Mayaud, and Brent Taylor were responsible for data handling and processing.
  • All investigators contributed to the writing of the paper.

Acknowledgments

  • The authors thank Nick Andrews (CDSC) for his help with statistical analysis, Andrew Lloyd Evans (neurodevelopmental paediatrician) and Sarah Willenberg (speech therapist) for advice, and Ioanna Kontagianni and Ekundayo Ajani-Obe for help with piloting and data collection.
  • The study was funded by the Medicines Control Agency.

Did you find this useful? Give us your feedback

Citations
More filters
Journal ArticleDOI
TL;DR: The approach of GRADE to rating quality of evidence specifies four categories-high, moderate, low, and very low-that are applied to a body of evidence, not to individual studies.

5,228 citations

Journal ArticleDOI
TL;DR: There is evidence that the broadening of the concept, the expansion of diagnostic criteria, the development of services, and improved awareness of the condition have played a major role in explaining this increase, although it cannot be ruled out that other factors might have also contributed to that trend.
Abstract: This article reviews the results of 43 studies published since 1966 that provided estimates for the prevalence of pervasive developmental disorders (PDDs), including autistic disorder, Asperger disorder, PDD not otherwise specified, and childhood disintegrative disorder. The prevalence of autistic disorder has increased in recent surveys and current estimates of prevalence are around 20/10,000, whereas the prevalence for PDD not otherwise specified is around 30/10,000 in recent surveys. Prevalence of Asperger disorder is much lower than that for autistic disorder and childhood disintegrative disorder is a very rare disorder with a prevalence of about 2/100,000. Combined all together, recent studies that have examined the whole spectrum of PDDs have consistently provided estimates in the 60-70/10,000 range, making PDD one of the most frequent childhood neurodevelopmental disorders. The meaning of the increase in prevalence in recent decades is reviewed. There is evidence that the broadening of the concept, the expansion of diagnostic criteria, the development of services, and improved awareness of the condition have played a major role in explaining this increase, although it cannot be ruled out that other factors might have also contributed to that trend.

1,815 citations

Journal ArticleDOI
TL;DR: There is evidence that changes in case definition and improved awareness explain much of the upward trend of rates in recent decades, however, available epidemiological surveys do not provide an adequate test of the hypothesis of a changing incidence of PDDs.
Abstract: This paper was commissioned by the committee on the Effectiveness of Early Education in Autism of the National Research Council (NRC). It provides a review of epidemiological studies of pervasive developmental disorders (PDD) which updates a previously published article (The epidemiology of autism: a review. Psychological Medicine 1999; 29: 769–786). The design, sample characteristics of 32 surveys published between 1966 and 2001 are described. Recent surveys suggest that the rate for all forms of PDDs are around 30/10,000 but more recent surveys suggest that the estimate might be as high as 60/10,000. The rate for Asperger disorder is not well established, and a conservative figure is 2.5/10,000. Childhood disintegrative disorder is extremely rare with a pooled estimate across studies of 0.2/10,000. A detailed discussion of the possible interpretations of trends over time in prevalence rates is provided. There is evidence that changes in case definition and improved awareness explain much of the upward trend of rates in recent decades. However, available epidemiological surveys do not provide an adequate test of the hypothesis of a changing incidence of PDDs.

1,607 citations


Cites background from "Autism and measles, mumps, and rube..."

  • ...…screening + 57.9 follow-up identification Fombonne et al., England & Wales 10,438 5–15 national household survey 26.1 2001 of psychiatric disorders Taylor et al., 1999 North Thames 490,000 0–16 administrative records 10.1 US studies Bertrand et al., 2001 Brick Township, NJ 8,896 3–10 multiple…...

    [...]

Journal ArticleDOI
TL;DR: In this paper, the emergence and development of active "self-and-other" awareness in infancy is examined and the importance of its motives and emotions to mental health practice with children.
Abstract: We review research evidence on the emergence and development of active "self-and-other" awareness in infancy, and examine the importance of its motives and emotions to mental health practice with children. This relates to how communication begins and develops in infancy, how it influences the individual subject's movement, perception, and learning, and how the infant's biologically grounded self-regulation of internal state and self-conscious purposefulness is sustained through active engagement with sympathetic others. Mutual self-other-consciousness is found to play the lead role in developing a child's cooperative intelligence for cultural learning and language. A variety of preconceptions have animated rival research traditions investigating infant communication and cognition. We distinguish the concept of "intersubjectivity", and outline the history of its use in developmental research. The transforming body and brain of a human individual grows in active engagement with an environment of human factors--organic at first, then psychological or inter-mental. Adaptive, human-responsive processes are generated first by interneuronal activity within the developing brain as formation of the human embryo is regulated in a support-system of maternal tissues. Neural structures are further elaborated with the benefit of intra-uterine stimuli in the foetus, then supported in the rapidly growing forebrain and cerebellum of the young child by experience of the intuitive responses of parents and other human companions. We focus particularly on intrinsic patterns and processes in pre-natal and post-natal brain maturation that anticipate psychosocial support in infancy. The operation of an intrinsic motive formation (IMF) that developed in the core of the brain before birth is evident in the tightly integrated intermodal sensory-motor coordination of a newborn infant's orienting to stimuli and preferential learning of human signals, by the temporal coherence and intrinsic rhythms of infant behaviour, especially in communication, and neonates' extraordinary capacities for reactive and evocative imitation. The correct functioning of this integrated neural motivating system is found to be essential to the development of both the infant's purposeful consciousness and his or her ability to cooperate with other persons' actions and interests, and to learn from them. The relevance of infants' inherent intersubjectivity to major child mental health issues is highlighted by examining selected areas of clinical concern. We review recent findings on postnatal depression, prematurity, autism, ADHD, specific language impairments, and central auditory processing deficits, and comment on the efficacy of interventions that aim to support intrinsic motives for intersubjective communication when these are not developing normally.

1,355 citations


Cites background from "Autism and measles, mumps, and rube..."

  • ...A number of recent reports suggest that the numbers of autistic children in the population may be increasing, and it appears that this is not simply a consequence of improved case assessment or changes in diagnostic criteria (Department of Developmental Services Report, 1999; Taylor et al., 1999)....

    [...]

Journal ArticleDOI
TL;DR: Systematic review authors and guideline developers may also consider rating up quality of evidence when a dose-response gradient is present, and when all plausible confounders or biases would decrease an apparent treatment effect, or would create a spurious effect when results suggest no effect.

873 citations


Cites result from "Autism and measles, mumps, and rube..."

  • ...Subsequent observational studies failed to confirm the association [25,26]....

    [...]

References
More filters
Journal ArticleDOI
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

Journal ArticleDOI
TL;DR: Pertussis incidence was 10 to 100 times lower in countries where high vaccine coverage was maintained than in countriesWhere immunisation programs were compromised by anti-vaccine movements, showing that these vaccines continue to have an important role in global immunisation.

613 citations

Journal ArticleDOI
TL;DR: A new method for active post-marketing surveillance of vaccine safety based on patient records is described, finding an increased relative incidence for convulsions 0-3 days after DTP vaccination.

321 citations

Journal ArticleDOI
TL;DR: In this paper, a method is described for estimating the relative incidence of clinical events in defined time intervals after vaccination compared to a control period using only data on cases, derived from a Poisson cohort model by conditioning on the occurrence of an event and on vaccination histories.
Abstract: A method is described for estimating the relative incidence of clinical events in defined time intervals after vaccination compared to a control period using only data on cases. The method is derived from a Poisson cohort model by conditioning on the occurrence of an event and on vaccination histories. Methods of analysis for event-dependent vaccination histories and survival data are discussed. Asymptotic arguments suggest that the method retains high efficiency relative to the full cohort analysis under conditions which commonly apply to studies of vaccine safety.

291 citations

Frequently Asked Questions (3)
Q1. What are the contributions in this paper?

Clustering of onsets within defined postvaccination periods was investigated by the case-series method. 

The authors undertook an epidemiological study to investigate whether measles, mumps, and rubella (MMR) vaccine may be causally associated with autism. 

No significant temporal clustering for age at onset of parental concern was seen for cases of core autism or atypical autism with the exception of a single interval within 6 months of MMR vaccination.