Older fathers may face higher risks than previously thought for having children with psychiatric problems, including bipolar disorder, autism and attention deficits, according to the largest study to examine the potential links.
American and Swedish researchers examined data on more than 2.6 million Swedes born from 1973-2001. Men who fathered kids after age 24 faced increasing odds for having children with psychiatric problems or academic difficulties, with the greatest risks seen at age 45 and older.
The results add to evidence challenging the notion that men's sperm are timeless, but this kind of research isn't proof. And by no means are children of older dads certain to have problems. Absolute risks were small -- less than 1 percent of kids of older dads had autism, attention deficit-hyperactivity disorder or bipolar disorder; and less than 4 percent had schizophrenia or fell victim to substance abuse or attempted suicide.
Academic difficulties were more common but still didn't affect most kids of older dads.
Even so, the magnitude of increased risks faced by kids born to dads aged 45 and older versus dads aged 20 to 24 was surprising, said lead author Brian D'Onofrio, an associate professor in the psychological and brain sciences department at Indiana University.
Compared with kids of the youngest dads, those fathered by men at age 45 and older faced risks almost 25 times greater for bipolar disorder; 13 times greater for ADHD; more than three times greater for autism; almost three times greater for suicide attempts; and about two times greater for schizophrenia and substance abuse.
The study was published online Wednesday in JAMA Psychiatry.
Molecular geneticist Simon Gregory, an associate professor at Duke University, called the new study impressive because of its size and depth -- the authors had access to a registry of most births in Sweden over more than 20 years, along with reams of data on psychiatric treatment, education and social welfare.
Still, Gregory said, "There's no reason to ring the alarm bells that older men shouldn't have kids" unless the results are replicated in additional research and molecular evidence is found.
D'Onofrio said the researchers took into account several factors that could have influenced the results, including the mothers' age at conception, parents' education and history of psychiatric problems, and siblings' health, and still found strong risks linked with older men.
"People frequently ask me, 'What's the safe age'" to father children, but the answer isn't clear-cut, D'Onofrio said. "There is no threshold where on one side it's safe and on the other side it's problematic."
He's among scientists who think the reason risks may increase with advancing age is that sperm are continually produced throughout men's lives and mutations may occur each time cells divide to create new sperm.
By contrast, women are born with a set number of eggs that become susceptible to certain genetic mutations, including those that cause Down syndrome, as women age. Other research has suggested women's age might play a role in autism and other disorders, but fathers' advanced age wasn't considered a potential risk until fairly recently.
Dr. Christopher Pittenger, a Yale University expert in psychiatric disorders, called the results convincing and said it's likely that many genetic mutations linked with older age contribute to the conditions studied, but that other factors also play a role.