In the largest analysis of its kind, researchers in Molecular Psychiatry today have perhaps shined some further light on the complex mystery that is autism.

Their study, poring over the medical records of more than 5.7 million children in five countries, purports to show a significant link between the age of a child’s parents at birth and later risk of developing an autism spectrum disorder (ASD). "Though we’ve seen research on autism and parental age before, this study is like no other,” said study author and epidemiologist Dr. Michael Rosanoff in a press statement. "By linking national health registries across five countries, we created the world's largest data set for research into autism's risk factors. The size allowed us to look at the relationship between parents' age and autism at a much higher resolution - under a microscope, if you will." Rosanoff is currently the director of public health research at Autism Speaks — an autism advocacy organization now in its tenth year of existence.

The authors focused on Denmark, Norway, Sweden, Israel, and Western Australia for their study, observing the autism rates of 5,766,794 children born between 1985 to 2004, depending on the nation. The children were followed until 2004 in Western Australia, 2006 in Israel, and 2009 in Denmark, Norway, and Sweden. Ultimately, 30,902 children were diagnosed with ASD in their sample. And from there, after adjusting for confounding factors, the authors were able to detect a noticeable influence of parental age on autism risk.

The lowest risk of autism was seen among similarly aged parents in their 20’s. Building on earlier research, they found a strong association with older fathers, with the autism rate 66 percent higher among children of fathers aged 50 or older, compared to those born to fathers in their 20’s. But moms over the age of 40 were also 15 percent more likely to have a child develop ASD than their younger counterparts. Teen pregnancies were similarly 18 percent more likely to result in an autistic child than the 20-something mom, a finding that hadn’t been definitively shown before. "We’d definitely like to be able to understand how and why younger moms might be more at risk," Rosanoff told Medical Daily.

These risks were independent of one another, but with the data available to them, the researchers were also able to study whether circumstances like a large age gap between the parents or having two older parents could also contribute to autism. "The risk was highest when both parents were older, but the risk was also increased among disparately aged parents," the authors wrote. These gaps (10 years or more) weren’t entirely explained by the age of one older parent alone, which suggests that these May-December romances have "other socio-economic (SES), genetic, and/or psychological characteristics that increase their risk of having children with ASD."

Though the exact relationship between age and ASD remains somewhat elusive, it is believed that the increased chance of either sperm or egg mutations among older parents may partially explain the link. There might also be a social component. "Social phobia and traits such as shyness and aloofness that may limit cross-sex interactions have been described for parents of children with ASD," the authors wrote. "These factors could influence the age when a person establishes a relationship and has children, confounding the association between parental age and risk of ASD."

Because of the scale of their study, a million-dollar and three-year long project funded by Autism Speaks, the authors are confident about their conclusions. "We’re now able to say that advanced parental age is a risk factor," Rosanoff told Medical Daily. Though many experts have concluded that the documented rise in ASD diagnoses over the past few decades has largely been due to better diagnostic and screening tools for autism, the fact that people are now having children at an older age may also partially explain the rise, Rosanoff said.

However frightening these numbers and percentages might seem to any potential parents-to-be, it should be noted that the absolute risk of ASD (one in every 68 children) remains low. "Risk factors are not causes, but with such a large dataset showing this age association, we’ll be better able to explore the mechanisms behind autism and discover new avenues for research," Rosanoff said. He predicts that there will be little change in how doctors discuss family planning with older individuals, who are already warned about the greater risk of developmental conditions like ASD when having children.

Perhaps the most important aspect of this study is the fact that others will be able to look at the vast amounts of data collected by the authors and perform their own independent analyses, possibly looking at factors such as the length of pregnancy on autism risk, Rosanoff said. And in that respect, it seems that this study might be a pivotal stepping stone to a brighter future for the autism community.

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Source: Sandin S, Schendal D, Magnusson P, et al. Autism risk associated with parental age and with increasing difference in age between the parents. Molecular Psychiatry. 2015