NEW YORK (Reuters Health) - Women who want to become mothers have long been told to heed the ticking of their biological clocks. Now a large Scandinavian study adds to evidence that men need to wake up and pay attention too.

Based on millions of children born in Sweden since the 1970s, researchers say those born to fathers older than 45 were significantly more likely to develop autism, bipolar disorder, attention deficit hyperactivity disorder and schizophrenia than those born to much younger fathers.

The analysis of all the births in Sweden over 28 years also found that children of older fathers were at heightened risk for substance abuse, suicide and academic failure.

"Historically, the focus has been on the mothers' age at childbirth," lead author Brian D'Onofrio told Reuters Health. "This study is adding to a growing body of research that suggests we also need to consider fathers' age at childbearing."

In the largest study to date on the effects of paternal age, D'Onofrio, an Indiana University psychologist, worked with Karolinska Institute researchers to analyze the civil and medical records of more than 2.6 million children born in Sweden between 1973 and 2001.

Several past studies have suggested that the age of a child's father - and even of its grandfather - can affect many aspects of the child's physical and psychological health for a lifetime (see Reuters article of March 20, 2013, here: http://reut.rs/1crroRh).

D'Onofrio and his colleagues wanted to look specifically at mental health in kids born to older fathers and began by comparing all the kids in their data pool to each other and seeing which children were most at risk of specific psychological disorders.

Fathers aged 45 to 79 years old were considered older, and the average age of older dads in the study was 49, D'Onofrio said. The younger fathers were 20 to 24 years old.

In their analysis, the researchers also wanted to eliminate social and environmental factors that could influence how kids turned out, so they compared individual children to their own eldest sibling - born when the parents were potentially much younger - as well.

In that comparison, the children born to older fathers were 25 times more likely to be diagnosed with bipolar disorder, 13 times more likely to be diagnosed with attention deficit hyperactivity disorder and 3.5 times more likely to suffer from autism than children born to fathers aged 20 to 24.

Children of older fathers also were more than twice as likely to attempt suicide and to become substance abusers, 1.6 times more likely to receive failing grades and 1.7 times more likely to drop out of school, the team reported in JAMA Psychiatry.

D'Onofrio said his findings from the sibling comparisons so "shocked" him that he spent months adding new variables to see if he could shrink the discrepancies or make them disappear. He could not.

Nonetheless, he pointed out, the chance of an older father having a mentally ill child remains small.

The study found 2,424 cases of autism out of about 900,000 children born between the years 1992 and 2001 and 6,819 cases of bipolar disorder out of 2.3 million children born from 1973 to 1997.

"We are not saying that all children born to older men are going to have psychiatric problems," D'Onofrio said. "Couples, along with their doctors and society at large, need to consider the advantages and disadvantages of delaying childbearing."

"How that plays out in terms of medical practice is certainly up for debate," D'Onofrio said.

Dr. Fred Volkmar, a psychiatrist and director of the Child Study Center at the Yale School of Medicine said the new study would not change his advice to prospective parents. "Any time you have a baby, there's risk," he said.

Epidemiologist Irva Hertz-Picciotto of the University of California, Davis, agrees there's evidence that paternal age may contribute to the development of autism, which she has studied extensively. But Hertz-Picciotto, who was not involved in the new study, told Reuters Health she thinks the sibling comparisons overstate the effect of paternal age because mothers' and fathers' ages are so interrelated.

"If the father has aged, so has the mother," she said. "From my perspective, that's a shaky analysis."

The new study also did not examine the possible role of older couples' use of infertility treatments on childhood mental illness, though D'Onofrio said the researchers plan to do that analysis.

The birth rate for U.S. women aged 40 to 44 years old rose by 2 percent a year from 2000 to 2012, according to government statistics. Average childbearing age has increased steadily for both men and women since the 1970s, with the average age increasing four years for women and three years for men, D'Onofrio said.

A previous study of Icelandic children diagnosed with autism and schizophrenia identified paternal age at conception as the single largest risk factor for passing on new gene mutations (see Reuters article of August 22, 2012, here: reut.rs/1cq3AYg).

In that study, about two more new gene mutations appeared in offspring for every year of increase in a father's age - meaning the number of new mutations passed on by fathers would double every 16.5 years from puberty onwards.

That possible explanation the new study's results makes sense to Volkmar. "As fathers get older, their sperm basically degrades. There is potential for small errors to creep in," he said, but other mechanisms could also be at work.

"It's not impossible," he said, "that older fathers are getting married later because they're strange people, and it takes them longer to find a mate."

SOURCE: bit.ly/1mHPKdH JAMA Psychiatry, online February 26, 2014.

(This story has been corrected in paragraphs 16 and 17 to clarify attribution of quotes)