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Children in Denmark receiving the measles-mumps-rubella (MMR) vaccine had no extra risk of developing autism, even among those considered especially vulnerable to the neurodevelopmental condition, researchers said.

In a nationwide cohort of 657,461 children, some 6,500 were diagnosed with autism during a 10-year follow-up period, for an incidence rate of 129.7 per 100,000 person-years, reported Anders Hviid, DrMedSci, of Statens Serum Institut in Copenhagen, and colleagues.

That rate was slightly lower than for unvaccinated kids (fully adjusted HR 0.93, 95% CI 0.85-1.02), the researchers wrote in .

When further broken down by sex, receipt of the MMR vaccine was linked to a reduced risk of autism for girls compared with boys (aHR 0.79 95% CI 0.64-0.97). (Copies of the Annals paper distributed to the media lacked the corresponding hazard ratio for boys however, graphs of cumulative incidence show slightly lower autism rates for vaccinated versus unvaccinated boys with no autistic siblings, and slightly higher rates for vaccinated boys who did have siblings with autism.) Receiving the MMR vaccine was also tied to a reduced risk for developing autism in children born from 1999-2001 compared with the 2002-2004, 2005-2007, and 2008-2010 birth cohorts (aHR 0.84, 95% CI 0.73-0.96).

The MMR vaccine also didn't increase the risk of developing autism in other subgroups of children assessed, including kids who had autistic siblings, received other vaccines in early childhood, or were considered to be at high-risk for autism.

Independent of MMR vaccination status, the variables that were related to the highest risk for a child developing autism were the following:

• Male sex: HR 4.02 (95% CI 3.78-4.28)
• Born in a late birth cohort (2008-2010): HR 1.34 (95% CI 1.18-1.52)
• No early childhood vaccinations: HR 1.17 (95% CI 0.98-1.38)
• Siblings with autism at study entry: HR 7.32 (95% CI 5.29-10.12)

"We previously addressed this issue in a similar but of 573,303 Danish children," Hviid and co-authors explained, adding that "[r]eassuringly, the main results are similar between the two studies, which supports the internal and external validity of both."

For this analysis, the researchers gathered data from the Danish Civil Registration System from 1999 to 2010, which contained information on MMR vaccine status, receipt of other childhood vaccines, diagnosis of autism, sibling diagnosis of autism, as well as other risk factors for autism such as smoking during pregnancy, parental age, and 5-minute Apgar score.

As part of the voluntary -- and free -- Danish childhood vaccination program, the first dose of the MMR vaccine is given at age 15 months, with a second dose at age 12 years. However, starting in 2008, the second dose is now given at age 4 years, with boosters given in later childhood. During this study period, the MMR vaccine administered contained the vaccine strains Schwarz (measles, 2000 to 2007) or Ender's Edmonton (measles, 2008–2013), Jeryl Lynn (mumps), and Wistar RA 27/3 (rubella).

In an , Saad B. Omer, MBBS, MD, PhD, of Emory University's Rollins School of Public Health, and Inci Yildirim, MD, PhD, MSc, of Emory School of Medicine in Atlanta, praised Hviid's group for adding yet another study to the literature refuting the original -- and now retracted -- that initially reported on an autism and MMR vaccine link.

Omer and Yildirim noted that the use of the Danish Psychiatric Central register allowed for the researchers to identify subgroups of children who were at a higher risk for autism, and determine that the MMR vaccine still wasn't tied to an increased risk for developing autism in certain subgroups, which was a limitation that previous studies failed to address.

"In the context of this new study, and given that mainstream studies have consistently pointed toward a lack of association between MMR vaccine and autism, a couple of questions arise," the editorialists wrote, posing the following questions. "First, is there sufficient uncertainty to warrant additional studies? Second, what impact will the accumulating evidence refuting an MMR-autism association have on the public perception of vaccine safety?"

"It has been said that we now live in a "fact-resistant" world where data have limited persuasive value. So how do physicians and public health officials debunk the MMR-autism myth?" Omer and Yildirim continued. In order to address this issue, they recommend clearly labeling myths as such when addressing these misperceptions about vaccines.

The editorialists also advised that it's not necessary to "rebut every piece of misinformation," and recommended a for clinicians seeking to answer patients' vaccine-safety questions.