The Father Factor: Advanced Paternal Age

We are used to the idea that advanced age of mothers places children at risk for Downs' Syndrome. New evidence is coming to light that the advanced age of fathers may be a factor as well. This article from Scientific American is based on the Israeli study I have already reported on this blog, here, here, here and here.
But the article has some new info as well:

Researchers had analyzed medical records in Israel, where all young men and most women must report to the draft board for mandatory medical, intelligence and psychiatric screening. They found that children born to fathers 40 or older had nearly a sixfold increase in the risk of autism as compared with kids whose fathers were younger than 30. Children of fathers older than 50—that includes me—had a ninefold risk of autism.

The researchers said that advanced paternal age, as they call it, has also been linked to an increased risk of birth defects, cleft lip and palate, water on the brain, dwarfism, miscarriage and “decreased intellectual capacity.”

What was most frightening to me, as someone with mental illness in the family, is that older fatherhood was also associated with an increased risk of schizophrenia. The risk rises for fathers with each passing year. The child of a 40-year-old father has a 2 percent chance of having schizophrenia—double the risk of a child whose father is younger than 30. A 40-year-old man’s risk of having a child with schizophrenia is the same as a 40-year-old woman’s risk of having a child with Down syndrome....
a 1912 study not(ed) that a form of dwarfism called achondroplasia was more common among the last-born children in families than among the first-born. Weinberg didn’t know why that was so, but he speculated that it might be related to the age of the parents, who were obviously older when their last children were born. Weinberg’s prescient observation was confirmed decades later when research showed that he was half right: the risk of dwarfism rose with the father’s age but not the mother’s.

Since then, about 20 inherited ailments have been linked to paternal age, including progeria, the disorder of rapid aging, and Marfan syndrome, a disorder marked by very long arms, legs, fingers and toes, as well as life-threatening heart defects. More recent studies have linked fathers’ age to prostate and other cancers in their children. And in September 2008 researchers linked older fathers to an increased risk of bipolar disorder in their children.

Read it all here.

Advanced Paternal Age and Autism

An on-line friend has been compiling research and references on the impact of advance paternal age on children. There is evidence that older fathers are statistically more likely to have children with conditions such as schizophrenia and autism. I have alluded briefly to this research in some of my speeches and articles, such as this one.
This compilation of research runs to 223 pages. If anyone is interested in having this report, I will gladly forward it along to you.

Autism and Advanced Parental Age

Regular readers of this blog know that I have an interest in everything relating to fertility, and to delayed child-bearing. Here is more evidence that advanced paternal age may be a factor in a child's risk of autism. From the abstract:

After adjustment for the other parent's age, birth order, maternal education, and other covariates, both maternal and paternal age were independently associated with autism (adjusted odds ratio for maternal age 35 vs. 25–29 years = 1.3, 95% confidence interval: 1.1, 1.6; adjusted odds ratio for paternal age 40 years vs. 25–29 years = 1.4, 95% confidence interval: 1.1, 1.8). Firstborn offspring of 2 older parents were 3 times more likely to develop autism than were third- or later-born offspring of mothers aged 20–34 years and fathers aged <40 years (odds ratio = 3.1, 95% confidence interval: 2.0, 4.7). The increase in autism risk with both maternal and paternal age has potential implications for public health planning and investigations of autism etiology.

This differs from other studies I have posted, in that the mothers' age appears to be a risk factor, as well as the fathers' age.
We have been trying to fool Mother Nature by postponing fertility indefinitely. Women have learned to their sorrow that this is not always possible: advanced maternal age increases the risk of infertility. So it is now interesting to see that advanced paternal age can be a problem as well.
For those who are new to this blog, here is the theory: as a man ages, his "fertility" doesn't necessarily decline, in that his sperm count may be just fine. But it appears that when the DNA replicates, it does not replicate precisely. The older the man is, the greater the likelihood of small genetic defects appearing in his DNA as it replicates. When I say "small" genetic defects, I mean that they are not substantial enough to be fatal to the infant. But, these genetic defects are thought to be the cause of the increased risk of not only autism, as observed in this study, but also schizophrenia and cancer later in life as well.



I have posted evidence

Male Biological Clock

We are all familiar with teh fact that women's fertility declines with age. We are now discovering that male fertility does as well. And worse, the damage to male sperm may do more than reduce the likelihood of conception. Advanced paternal age has been implicated in a number of birth defects. From an article in Psychology Today:

Nonetheless, a virtual tidal wave of recent research has made it irrefutable: Not only does male fertility decrease decade by decade, especially after age 35, but aging sperm can be a significant and sometimes the only cause of severe health and developmental problems in offspring, including autism, schizophrenia, and cancer. The older the father, the higher the risk. But what's truly noteworthy is not that infertility increases with age—to some degree, we've known that all along—but rather that older men who can still conceive may have such damaged sperm that they put their offspring at risk for many types of disorders and disabilities.

The mechanism seems to be that as men age, their DNA does not replicate as accurately as at earlier ages. Therefore, small abnormalities in the genetic struction which are not large enough to be fatal, can cause a wide array of damage to the child:

These mutations could reflect the differences in male and female reproduction, notes Jabs (Ethylin Wang Jabs, professor of pediatric genetics at Johns Hopkins University). By the time females reach their teen years, their eggs have already been formed—just one new egg matures each month. Men, on the other hand, produce millions of sperm cells every time they ejaculate. After each ejaculation, they must literally replicate those cells, and each replication multiplies the chance for a DNA "copy error"—a genetic chink in the sperm DNA. The more ejaculations a man produces, the greater the chance for chinks to arise, leading to increased point mutation and thus increased infertility and birth defects. While a woman's reproductive capacity halts more or less abruptly after all her eggs have been used up somewhere in their forties or fifties, men experience a longer, more gradual winnowing and disintegration. "We believe that something in men's DNA replication machinery keeps becoming less efficient and less accurate with age, and the problems accumulate," says Jabs.

This is yet another unintended consequence of delaying childbirth, a delay made possible by conctraception. We are increasingly organizing society around the premise that sex is essentially a sterile activity, with childbearing thrown in as an after-thought, if you happen to like that sort of thing. Widespread access to contraception has made indefinite postponement of childbearing the norm, not the exception among the educated classes.
It is time to rethink this.

Autism, Schizophrenia and advanced paternal age

A reader sent me these links on these subjects. I pass them along to my readers. Make of them what you will. I find this fascinating, and plan to keep my ear to the ground on this topic.
Dr J
http://themalebiologicalclock.blogspot.com/
autism-prevention
parentalagepostings
howoldistooold
ebdblog.com/paternalage

Many of these blogs are citing the same studies, but there are some differences in perspective among them. I report them for what they may be worth to my readers.