Does the mmr vaccine cause autism?

New research published in Annals of Internal Medicine provides further evidence that there is no connection between the measles, mumps, rubella vaccine and autism, even in children with other risk factors for the condition.

“The hypothesized link between the measles, mumps, rubella (MMR) vaccine and autism continues to cause concern and challenge vaccine acceptance almost two decades after the controversial and later retracted Lancet paper from 1998, even though observational studies have not been able to identify an increased risk for autism after MMR vaccination,” Anders Hviid, DrMedSci, from Statens Serum Institut, Copenhagen, Denmark, and colleagues wrote.

Vaccine hesitancy has been recognized by the WHO as one of the top 10 threats to global health in 2019. Cases of measles has increased 30% globally, according to WHO, and in January, Washington declared a state of emergency after 34 people were infected with measles due to anti-vaccine fervor.

Social media has notably played a role in the anti-vaccine movement and outlets, such as YouTube, are now taking action by blocking anti-vaccine ads.

Hviid and colleagues investigated the association between MMR vaccine and autism in a more recent and larger cohort of children from Denmark over a longer duration of time.

The researchers studied 657,461 children born in Denmark between 1999 and 2010. Participants were followed from 1 year of age through Aug. 31, 2013.

Does the MMR Vaccine Cause Autism?

New research published in Annals of Internal Medicine provides further evidence that there is no connection between the measles, mumps, rubella vaccine and autism, even in children with other risk factors for the condition.

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Data on MMR vaccination, autism diagnoses, other childhood vaccines, sibling history of autism, and autism risk factors were linked to children in the study cohort using Danish population registries. The analysis was adjusted for age, birth year, sex, other childhood vaccines, sibling history of autism and autism risk factors.

Autism was diagnosed in 6,517 participants (incidence rate, 129.7 per 100,000 person-years).

The fully adjusted HR for autism was 0.93 (95% CI, 0.85-1.02) in MMR-vaccinated children compared with MMR-unvaccinated children.

Additionally, there was no increased risk for autism associated with MMR vaccination in subgroups of children with sibling history of autism, autism risk factors or other childhood vaccinations, or during certain time frames after vaccination, according to the researchers.

“A main reason that parents avoid or are concerned about childhood vaccinations has been the perceived link to autism,” Hviid and colleagues concluded.

“Our study adds to previous studies through significant additional statistical power and by addressing hypotheses of susceptible subgroups and clustering of cases.

We believe that our results offer reassurance and provide reliable data on which clinicians and health authorities can base decisions and public health policies.” – by Alaina Tedesco

Disclosures: Hviid reports receiving grants from Novo Nordisk Foundation. Please see study for all other authors’ relevant financial disclosures.

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No MMR Vaccine-Autism Link in Large Study

Study of over 95,000 children included 15,000 unvaccinated 2 to 5 year olds and nearly 2,000 kids already considered at high risk for autism

In the largest-ever study of its kind, researchers again found that the measles-mumps-rubella (MMR) vaccine did not increase risk for autism spectrum disorder (ASD). This proved true even among children already considered at high risk for the disorder.

In all, the researchers analyzed the health records of 95,727 children, including more than 15,000 children unvaccinated at age 2 and more than 8,000 still unvaccinated at age 5. Nearly 2,000 of these children were considered at risk for autism because they were born into families that already had a child with the disorder.

The report appears today in JAMA, the Journal of the American Medical Association. 

“Consistent with studies in other populations, we observed no association between MMR vaccination and increased ASD risk,” the authors write. “We also found no evidence that receipt of either one or two doses of MMR vaccination was associated with an increased risk of ASD among children who had older siblings with ASD.”

New evidence confirms MMR vaccine is effective, does not cause autism

A new review of data from more than 20 million children shows that the MMR vaccine, which protects against measles, mumps, and rubella, is effective and not associated with autism.

Share on PinterestA new review confirms that the MMR vaccine is effective.

Health authorities licensed the MMR vaccine for use in 1971 after tests showed that adverse reactions from the combined vaccine were no greater than any from the existing, single vaccines.

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Governments have since rolled the vaccine out across the globe, leading to the eradication of measles in many countries, including the United States.

Despite this, the vaccine has been the subject of much controversy, in particular, due to a 1998 study linking the vaccine to autism. The study was later shown to be fraudulent and was discredited, but not before it received wide publicity, leading to public misconceptions about the vaccine.

An updated review of the evidence has now confirmed that the MMR vaccine is effective and not associated with autism.

The Cochrane Library, which surveys medical research to help health professionals make evidence-based decisions, has published the review.

The latest analysis follows a 2012 review, which concluded that there was good evidence for the safety and effectiveness of the MMR vaccine. This 2020 update includes 74 new studies that researchers have published since 2012.

“We wanted to assess the effectiveness, safety, and long- and short-term harms of the MMR vaccines in this updated review,” explains lead author, Dr. Carlo Di Pietrantonj of Italy’s Regional Epidemiology Unit, SeREMI.

The updated review includes data on three types of vaccine: MMR; MMRV, which is a combined vaccine that also protects against chickenpox (known clinically as varicella); and MMR+V, which is when healthcare professionals give the MMR vaccine and chickenpox vaccine separately but at the same appointment.

In total, the review included 138 studies with data from 23 million children. Some 63% of the studies assessed potential harms from the vaccines (13 million children), while the remaining 37% (10 million children) looked at how effective the vaccines were at preventing the respective diseases.

MMR Vaccine, Bowel Disease and Autism

  • Published: July 1998
  • Prescriber Update 16: 41–42 July 1998
  • Dr Osman Mansoor, Public Health Group, Ministry of Health

A small case series has found a temporal association between autism associated with bowel disease and MMR vaccine.

The evidence does not suggest that the vaccine causes autism. Public perception of risk can affect the uptake of vaccines and lead to an increase in vaccine-preventable disease. The Ministry continues to recommend immunisation, and does not consider autism a risk factor of MMR vaccine.

An 'early report' implicated measles-mumps-rubella (MMR) vaccine as a cause of autism.1 The report described 11 boys and one girl with variable bowel abnormalities and serious developmental regression (autism in nine cases).

Symptoms appeared one day to two months after immunisation.

The hypothesis put forward by the authors is that MMR vaccine causes inflammation or dysfunction of the intestine, increasing the absorption of non-permeable peptides, which in turn can cause serious developmental disorders.

Doubt cast on alleged link

The accompanying commentary cast doubt on the alleged link.2 The case series was subject to both selection and recall bias, the pathological findings were non-specific, there was no clear case definition and confirmatory virological studies had not been completed.

The commentary also noted that although the authors had found measles virus in inflammatory bowel disease, the investigations of other researchers were negative.

Indeed, the same edition of the Lancet included another study which failed to find measles virus genome in inflammatory bowel disease even though the researchers used a highly sensitive assay.

Unbalanced media coverage can have serious consequences

Last year the same authors claimed that MMR vaccine caused Crohn’s disease. This also received widespread media coverage despite evidence not supporting the claim. Since then, accumulating evidence against the link3 has been ignored by the media. The consequent decline in confidence in MMR vaccine has affected coverage in the United Kingdom.4

A recent editorial warns of the danger of repeating the harm caused in the United Kingdom from media reports in the 1970s about pertussis vaccine causing brain damage.5 As a result of the decline in pertussis immunisation, there were three major epidemics over 12 years causing over 300,000 notifications and at least 70 deaths.

No evidence to suggest MMR vaccine causes autism

On 23 March 1998, the British Medical Research Council held a meeting of experts who concluded that the available evidence does not indicate a link between measles, measles vaccine or MMR immunisation and either Crohn’s disease or autism. Two other studies have failed to show any association.6,7

The Ministry of Health also considers there is no evidence to suggest that there is a risk of autism from MMR vaccine.

Information contained in the Immunisation Choices booklet still represents an accurate description of the risks of immunisation compared to the disease.

High immunisation coverage is critical to disease control, especially at the tail-end of a measles epidemic that was limited through immunisation.

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References

  1. Wakefield AJ, Murch SH, Anthony A, et al. Ileal-lymphoid-nodular hyperplasia, non-specific colitis and pervasive developmental disorder in children. Lancet 1998;351:637-41.
  2. Chen RT, DeStefano F. Vaccine adverse events: causal or coincidental? Lancet 1998;351:611-2.
  3. Expanded programme on immunization (EPI). Association between measles infection and the occurrence of chronic inflammatory bowel disease. Wkly Epidemiol Rec 1998;73:33-9.
  4. Begg N, Ramsay M, White J, Bozoky Z. Media dents confidence in MMR vaccine. BMJ 1998;316:561.
  5. Nicoll A, Elliman D, Ross E. MMR vaccination and autism 1998. BMJ 1998;316:715-6.
  6. Payne C, Mason B. Autism, inflammatory bowel disease, and MMR vaccine. Lancet 1998;351:907.
  7. Fombonne E. Inflammatory bowel disease and autism. Lancet 1998;351:955.

Do Vaccines Cause Autism?

The research is clear: Vaccines don’t cause autism. More than a dozen studies have tried to find a link. Each one has come up empty.

The debate began in 1998 when British researchers published a paper stating that the measles-mumps-rubella (MMR) vaccine caused autism. The study looked at only 12 children, but it received a lot of publicity. At the same time, there was a rapid increase in the number of kids diagnosed with the condition.

The paper’s findings led other doctors to do their own research into the link between the MMR vaccine and autism. At least 12 follow-up studies were done. None found any evidence the vaccine caused autism.

An investigation into the 1998 study also uncovered a number of problems with how it was conducted. The journal that published it eventually retracted it. That meant the publication no longer stood by the results.

There were other problems, too. For example, investigators learned that a lawyer looking for a link between the vaccine and autism had paid the lead researcher more than £435,000 (equal to more than a half-million dollars).

A year after the British study, fears about a possible vaccine-autism link shifted from MMR to a substance used in some children’s vaccines. It was called thimerosal, and it contained mercury. That’s a metal that’s harmful to the brain and kidneys at high levels. Doctors used thimerosal to prevent the growth of bacteria and fungi in vaccines.

Measles, Mumps, Rubella Vaccination and Autism

The hypothesized link between the measles, mumps, rubella (MMR) vaccine and autism continues to cause concern and challenge vaccine acceptance almost 2 decades after the controversial and later retracted Lancet paper from 1998 (1), even though observational studies have not been able to identify an increased risk for autism after MMR vaccination. In a 2014 meta-analysis, 10 observational studies on childhood vaccines were identified: 5 cohort studies and 5 case–control studies (2). Of these, 2 cohort studies and 4 case–control studies specifically addressed MMR and autism, all reporting no association. This is consistent with more recent studies of note (3, 4).

We previously addressed this issue in a nationwide cohort study of 537 303 Danish children with 738 cases of autism spectrum disorders (5). In our cohort, MMR vaccination was not associated with autistic disorder (rate ratio, 0.92 [95% CI, 0.68 to 1.24]) or other autism spectrum disorders (rate ratio, 0.83 [CI, 0.65 to 1.07]).

In this study, we aimed to evaluate the association again in a more recent and nonoverlapping cohort of Danish children that has greater statistical power owing to more children, more cases, and longer follow-up.

A criticism of our and other previous observational studies has been that these did not address the concern that MMR vaccination could trigger autism in specific groups of presumably susceptible children, in contrast to all children (6); the current study addresses this concern in detail.

We evaluate the risk for autism after MMR vaccination in subgroups of children defined according to environmental and familial autism risk factors.

Another criticism has been that MMR is associated with a regressive form of autism, leading to a clustering of cases with onset shortly after MMR vaccination (7). We evaluate the risk for autism after MMR vaccination in specific periods in detail.

Ethical approval is not needed for register-based research in Denmark. The Danish Data Protection Agency approved the study.

We conducted a nationwide cohort study of all children born in Denmark of Danish-born mothers from 1 January 1999 through 31 December 2010.

We sourced the study cohort from the Danish Civil Registration System, which assigns a unique personal identification number to all people living in Denmark and keeps track of basic demographic information for each individual (8).

This unique identifier is used in all other national registries and allows for individual-level linkage of health-related information, including vaccinations and autism diagnoses.

The Danish childhood vaccination program is voluntary and free of charge. The mainstays of the early part of the Danish program are MMR and a diphtheria, tetanus, acellular pertussis, inactivated polio, and Haemophilus influenzae type b (DTaP-IPV/Hib) combination.

A first dose of MMR vaccine is offered at 15 months (MMR1), with a second dose (MMR2) at 12 years of age or, since 2008, at 4 years of age. The DTaP-IPV/Hib vaccine is offered in 3 doses at 3, 5, and 12 months. Boosters are offered later in childhood.

General practitioners administer all childhood vaccinations and are reimbursed when reporting these to the National Board of Health; these reports are included in the Danish National Health Service Register (9).

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We obtained individual-level information on MMR1 and MMR2 vaccinations and other childhood vaccinations administered in the first year of life.

There were no thimerosal-containing vaccines in the Danish program during the study period.

The specific MMR vaccine used in the study period contained the following vaccine strains: Schwarz (measles, 2000 to 2007) or Ender's Edmonton (measles, 2008–2013), Jeryl Lynn (mumps), and Wistar RA 27/3 (rubella).

Information on autism spectrum disorder diagnoses in the study period was obtained from the Danish Psychiatric Central Register (10). Child psychiatrists diagnose and assign diagnostic codes for this register, which contains information from psychiatric hospitals and psychiatric wards (inpatients and outpatients in the study period).

The coding classification used in the study period was the International Classification of Diseases, 10th Revision; we used the codes F84.0 (autistic disorder), F84.1 (atypical autism), F84.5 (Asperger syndrome), F84.8 (other pervasive developmental disorder), and F84.9 (unspecified pervasive developmental disorder).

We defined our main study outcome of autism as a diagnosis of any of these autism spectrum disorders.

From the Danish National Patient Register comprising diagnoses from all somatic departments, we obtained information on several syndromes and conditions with an inherent increased risk for autism (fragile X syndrome, tuberous sclerosis, Angelman syndrome, Down syndrome, DiGeorge syndrome, neurofibromatosis, Prader–Willi syndrome, and congenital rubella syndrome) (11). Children with any of these conditions were excluded from the study if the condition was diagnosed before their first birthday or censored at date of the diagnosis if it was made when the child was older than 1 year (14).

We included many autism risk factors for stratification and confounder adjustment, on the basis of a literature review on environmental autism risk factors and availability of data in our registers (12); these were maternal age, paternal age, smoking during pregnancy, method of delivery, preterm birth, 5-minute Apgar score, low birthweight, and head circumference. For variables with missing values, we included a missing value category in the analyses. Table 1 of the Supplement provides a complete list of variables with categorizations). These variables were obtained from the Danish Medical Birth Registry, which includes information on the parents and the newborn, pregnancy, date of birth, multiple births, gestational age, and vital status and other physical characteristics of the newborn (13).

From the Danish Civil Registration System, we obtained parental links to identify siblings (defined as common father and mother) for each cohort child. Cases of autism among siblings were identified similarly to the main study outcome.

The main goal of our modeling strategy was to evaluate whether the MMR vaccine increases the risk for autism in children, subgroups of children, and time periods after vaccination.

We defined subgroups according to 1) sibling history of autism (“genetic susceptibility”), sex, birth cohort, and prior vaccinations in the first year of life and 2) a summary index estimated from a disease risk model combining multiple environmental risk factors.

The motivation for a summary index was that the combination of several factors each associated with only a moderate risk increase in autism had the potential of identifying children at higher risk through multiple risk factors, in contrast to many stratified analyses of single moderate risk factors.

We analyzed the study cohort by using survival analysis (14). Children in the cohort contributed person-time to follow-up from 1 year of age and until a first diagnosis of autism, death, emigration, unexplained disappearance from the source registers, diagnoses of autism-associated conditions or syndromes, or end of the study on 31 August 2013.

The MMR vaccination status was considered a time-varying variable; children could contribute time as both unvaccinated and vaccinated in our study.

Using the cases of autism among siblings, we constructed a time-varying variable summarizing each child's sibling history of autism with the states “no siblings,” “siblings without autism,” or “siblings with at least one case of autism”; a missing value category covered the children who had unknown fathers. We used sibling history at study entry unless otherwise specified.

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