Large age-gaps between parents increase risk of autism in children

The study builds on the broader research of the International Collaboration for Autism Registry for Epidemiology (iCARE). The investigators looked at autism rates among 5,766,794 children – including more than 30,000 with autism – in Denmark, Israel, Norway, Sweden and Western Australia. The children were born between 1985 and 2004, and the researchers followed up on their development between 2004 and 2009, checking national health records for autism diagnosis.

“By combining information across five countries, we have created a valuable base for research into autism”, says Christina Hultman, a Professor of Psychiatric Epidemiology at Karolinska Institutet and one of the initiators of the iCare collaboration.

Previous studies have found links between parental age and increased risk of autism in children. However, many questions still remain. The goal of this new study was to determine whether advancing maternal or paternal ages independently increase autism risk – and to what extent each might do so.

Mother’s versus father’s age

Researchers identified and controlled for other age-related influences that might affect autism risk. When separating the influence of mother’s versus father’s age, they also adjusted for the potential influence of the other parent’s age.

“After finding that paternal age, maternal age and parental-age gaps all influence autism risk independently, we calculated which aspect was most important,” says Dr Sven Sandin,a statistician and epidemiologist at Karolinska Institutet, also affiliated to the Icahn School of Medicine at Mount Sinai in New York, US. “It turned out to be parental age, though age gaps also contribute significantly.”

Key findings:

• Autism rates were 66 percent higher among children born to dads over 50 years of age than among those born to dads in their 20s. Autism rates were 28 percent higher when dads were in their 40s versus 20s.
• Autism rates were 15 percent higher in children born to mothers in their 40s, compared to those born to moms in their 20s.
• Autism rates were 18 percent higher among children born to teen moms than among those born to moms in their 20s.
• Autism rates rose still higher when both parents were older, in line with what one would expect if each parent’s age contributed to risk.
• Autism rates also rose with widening gaps between two parents’ ages. These rates were highest when dads were between 35 and 44 and their partners were 10 or more years younger. Conversely, rates were high when moms were in their 30s and their partners were 10 or more years younger.

The higher risk associated with fathers over 50 is consistent with the idea that genetic mutations in sperm increase with a man’s age and that these mutations can contribute to the development of autism spectrum disorders (ASD). By contrast, the risk factors associated with a mother’s age remain unexplained, as do those associated with a wide gap between a mother and father’s age.

“These results suggest that multiple mechanisms are contributing to the association between parental age and ASD risk”, says Sven Sandin. “However, it is important to remember that the majority of children born to older or younger parents will develop normally.”

Christina Hultman and Sven Sandin are both affiliated to the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet. The study was funded Autism Speaks, which is the world’s leading autism science and advocacy organization. This news article is an edited version of a press release from Autism Speaks.

Publication

Autism risk associated with parental age and with increasing difference in age between the parents
Sandin Sven, Schendel Diana, Magnusson Patrik, Hultman Christina, Surén Pål, Susser Ezra, Grønborg Therese, Gissler Mika, Gunnes Nina, Gross Raz, Henning Maria, Bresnahan Micki, Sourander Andre, Hornig Mady, Carter Kim, Francis Richard, Parner Erik, Leonard Helen, Rosanoff Michael, Stoltenberg Camilla, Reichenberg Abraham
Molecular Psychiatry (2015) 1359-4184/15, online 9 June 2015