Vaccines are not associated with autism: An evidence-based meta-analysis of case-control and cohort studies (original) (raw)

Highlights

Abstract

There has been enormous debate regarding the possibility of a link between childhood vaccinations and the subsequent development of autism. This has in recent times become a major public health issue with vaccine preventable diseases increasing in the community due to the fear of a ‘link’ between vaccinations and autism. We performed a meta-analysis to summarise available evidence from case-control and cohort studies on this topic (MEDLINE, PubMed, EMBASE, Google Scholar up to April, 2014). Eligible studies assessed the relationship between vaccine administration and the subsequent development of autism or autism spectrum disorders (ASD). Two reviewers extracted data on study characteristics, methods, and outcomes. Disagreement was resolved by consensus with another author. Five cohort studies involving 1,256,407 children, and five case-control studies involving 9,920 children were included in this analysis. The cohort data revealed no relationship between vaccination and autism (OR: 0.99; 95% CI: 0.92 to 1.06) or ASD (OR: 0.91; 95% CI: 0.68 to 1.20), nor was there a relationship between autism and MMR (OR: 0.84; 95% CI: 0.70 to 1.01), or thimerosal (OR: 1.00; 95% CI: 0.77 to 1.31), or mercury (Hg) (OR: 1.00; 95% CI: 0.93 to 1.07). Similarly the case-control data found no evidence for increased risk of developing autism or ASD following MMR, Hg, or thimerosal exposure when grouped by condition (OR: 0.90, 95% CI: 0.83 to 0.98; p

=

0.02) or grouped by exposure type (OR: 0.85, 95% CI: 0.76 to 0.95; p

=

0.01). Findings of this meta-analysis suggest that vaccinations are not associated with the development of autism or autism spectrum disorder. Furthermore, the components of the vaccines (thimerosal or mercury) or multiple vaccines (MMR) are not associated with the development of autism or autism spectrum disorder.

Introduction

Over the past several years much concern has been raised regarding the potential links of childhood vaccinations with the development of autism and autism spectrum disorders (ASD). The vaccinations that have received the most attention are the measles, mumps, rubella (MMR) vaccine and thimerosal-containing vaccines such as the diphtheria, tetanus, pertussis (DPT or DT) vaccine. A rising awareness of autism incidence, prevalence, and the postulated causation of childhood vaccinations has led to both an increased distrust in the trade-off between vaccine benefit outweighing potential risks and an opportunity for disease resurgence. This is especially concerning given the fact that the CDC reported 17 measles outbreaks in the U.S. in 2011 and NSW, Australia also saw a spike in its measles notifications from late 2011 to mid-July 2012 [1], [2]. Vaccine-preventable diseases clearly still hold a presence in modern day society and the decision to opt out of MMR or other childhood vaccination schedules because of concerns regarding the development of autism should be properly evaluated with available evidence. To date there have been no quantitative data analysis pooling cohort and case-control studies that have assessed the relationship between autism, autistic spectrum disorder and childhood vaccinations.

This meta-analysis aims to quantitatively assess the available data from studies undertaken in various countries regarding autism rates and childhood vaccination so that the relationship between these two, whatever its significance, can be adequately substantiated.

Section snippets

Study protocol

We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to conduct our review and analysis [3], [4]. The PRISMA guidelines have been developed in an attempt to standardise reporting in systematic reviews and include a four-phase flow diagram as well as a checklist of 27 items deemed necessary for transparent reporting of results of meta-analyses. A systematic search of the databases Medline (from 1950), PubMed (from 1946), Embase (from 1949), and

Study selection

The search of Medline, PubMed, and Embase returned 519, 718, and 1133 results, respectively. After adjusting for duplicates, 1112 papers in total remained, 953 were excluded immediately on inspection of the abstracts as they clearly did not meet inclusion criteria, leaving 159 papers whose methods sections were analysed in more detail to determine suitability. No unpublished relevant studies were obtained. Five additional papers were found on examination of relevant reference lists. A further

Discussion

This meta-analysis of five case-control and five cohort studies has found no evidence for the link between vaccination and the subsequent risk of developing autism or autistic spectrum disorder. Subgroup analyses looking specifically at MMR vaccinations, cumulative mercury dosage, and thimerosal exposure individually were similarly negative, as were subgroup analyses looking specifically at development of autistic disorder versus other autistic spectrum disorder.

Four of the five cohort studies

Epilogue

As an epidemiologist I believe the data that is presented in this meta-analysis. However, as a parent of three children I have some understanding of the fears associated with reactions and effects of vaccines. My first two children have had febrile seizures after routine vaccinations, one of them a serious event. These events did not stop me from vaccinating my third child, however, I did take some proactive measures to reduce the risk of similar adverse effects. I vaccinated my child in the

Author contributions

Dr Guy D. Eslick had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Guy D. Eslick; acquisition of data: Luke Taylor, Amy L. Swerdfeger; analysis and interpretation of data: Guy D. Eslick; drafting of the manuscript: Luke Taylor, Amy L. Swerdfeger; critical revision of the manuscript for important intellectual content: Guy D. Eslick, Luke Taylor, Amy L. Swerdfeger; statistical

Conflict of interest statement

None.

References (36)

Meta-analysis in clinical trials

Controlled Clin Trials

(1986)

The file drawer problem and tolerance for null results

Psychol Bull

(1979)

MMR vaccination and pervasive developmental disorders: a case-control study

Lancet

(2004)

The combined measles, mumps, and rubella vaccines and the total number of vaccines are not associated with development of autism spectrum disorder: the first case-control study in Asia

Vaccine

(2012)

Unintended events following immunization with MMR: a systematic review

Vaccine

(2003)

Does the MMR triple vaccine cause autism?

Evid Based Healthc Public Health

(2004)

Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement

BMJ

(2009)

The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration

BMJ

(2009)

Understanding vaccine safety information from the Vaccine Adverse Event Reporting System

Pediatr Infect Dis J

(2004)

Vaccine Adverse Event Reporting System reporting source: a possible source of bias in longitudinal studies

Pediatrics

(2006)

Measuring inconsistency in meta-analyses

BMJ

(2003)

Bias in meta-analysis detected by a simple, graphical test

Br Med J

(1997)

A population-based study of measles, mumps, and rubella vaccination and autism

N Engl J Med

(2002)

MMR-vaccine and regression in autism spectrum disorders: negative results presented from Japan

J Autism Dev Disord

(2007)

Thimerosal exposure in infants and developmental disorders: a retrospective cohort study in the United Kingdom does not support a causal association

Pediatrics

(2004)

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