Older dads 'more likely' to have autistic grandkids ...

"Having an older grandfather 'raises autism risk'," the Daily Telegraph reports, saying that older fathers are much more likely to go on to have grandchildren with autism. However, this doesn't mean men should change their plans for having a family.

The association between fathers' ages and the likelihood of their children having autism has been seen before. This news comes from a study suggesting that the link may go back another generation. Men who had a son or daughter later in life were more likely to have a grandchild diagnosed with autism when compared with men who became fathers in their early twenties.

This association was particularly clear for men who had children after the age of 50. The odds of having a grandchild with autism increased by 67% when looking at the age of the child's father's father, and 79% when examining the age of the child's mother's father.

The researchers speculate that the association seen in the study may be caused by mutations in men's sperm cells that develop as they grow older, and that a certain proportion of these mutations may have an indirect impact on autism in later generations. But despite their findings, the researchers say that, "older men should not be discouraged to have children".

A single cause for autism, such as genetics, is unlikely. Several interacting risk factors for autistic spectrum conditions have been proposed. We don't yet know precisely what causes autism, so there's no need to plan when to have children based on the results of studies like this.

Where did the story come from?

The study was carried out by researchers from the Karolinska Institute in Sweden, King's College London, Mount Sinai School of Medicine in the US, and the University of Queensland in Australia. The research was funded by the Swedish Research Council, the Swedish Council for Working Life and Social Research, and the Karolinska Institute.

It was published in the peer-reviewed medical journal JAMA Psychiatry.

The research was covered appropriately in the media, with both BBC News and The Daily Telegraph pointing out that the results do not mean that older people should be discouraged from having children. The chances of a child being born with autism are quite small, despite more alarming figures of a 67-79% relative increase.

What kind of research was this?

This was a case-control study using data from patient records in Sweden. The study assessed the association between paternal age and autism among grandchildren.

As a case-control study, this research can only describe associations between age and autism risks two generations later. It cannot tell us conclusively that one causes the other, and can only speculate as to possible causes underlying the association.

What did the research involve?

Using the Swedish Patient Registry, researchers identified a large group of individuals diagnosed with childhood autism between 1987 and 2009 (the cases) and another group of individuals with no autism diagnosis (the controls).

Five controls were selected for each autism case, and were matched to the individual with autism according to gender and exact year of birth.

This means that if a boy born in 1995 was diagnosed with autism during childhood, the researchers selected five other boys born in 1995 who were not diagnosed with autism.

Autism was diagnosed by specialists and conformed to international definitions that excluded Asperger's syndrome.

For each of the case and control children, the researchers used the Swedish Multi-generation Register to collect data on the parents' ages at the time of the child's birth, as well as information on their grandfathers' ages at the time of their parents' birth.

Data from three generations was used in the analyses:

child's autism status (the main outcome)
parents' ages at the child's birth
grandparents' ages at the parent's birth

The researchers used this data to estimate the association between the age of a grandfather at the parent's birth and autism in the child. Two separate analyses were carried out:

the first assessed the impact of maternal grandfather age (that is, the grandfather's age when the child's mother was born)
the second assessed the impact of paternal grandfather age (the grandfather's age when the child's father was born)

They analysed grandfathers' ages separately by those:

less than 20 years old
20 and 24 years old (referent group)
25 to 29 years old
30 to 34 years old
35 to 39 years old
40 to 44 years old
45 to 49 years old
more than 50 years old

The odds of having a grandchild with autism were calculated for each grandfather age band. This was compared with the odds seen among grandfathers who were between 20 and 24 years old when the child's parent was born. This calculation provides an idea of the association between increasing grandfather paternal age and autism in the grandchild.

Several other variables (confounders) were included in the analysis to control for their affect on the relationship, including:

a family history of schizophrenia, bipolar disorder or autism
parental educational attainment (as a marker for the child's socioeconomic status)
place of residence

What were the basic results?

The original study included 9,868 children with an autism diagnosis and 49,340 children with no such diagnosis (the controls). Due to missing data on parental age among the parents and grandparents, as well as parental educational attainment, only 5,933 of the original cases (60%) and 30,904 of the original controls (63%) were included in the statistical analyses.

Men who had a daughter when they were younger than 20 years or between 25 and 29 had no significant difference in odds of having a grandchild with autism compared with men who had a daughter when they were between 20 and 24 years old.

At older ages, however, the odds of having a grandchild diagnosed with autism increased with increasing age. Compared with those aged between 20 and 24 when the child's mother was born, the odds of having a grandchild diagnosed were:

19% higher among those aged 30 to 34 years (odds ratio [OR] 1.19, 95% confidence interval [CI] 1.07 to 1.32)
31% higher among those aged 35 to 39 years (OR 1.31, 95% CI 1.15 to 1.49)
31% higher among those aged 40 to 44 years (OR 1.32, 95% CI 1.12 to 1.54)
34% higher among those aged 45 to 49 years (OR 1.34, 95% CI 1.07 to 1.67)
79% higher among those aged 50 years or more (OR 1.79, 95% CI 1.34 to 2.37)

A similar pattern emerged when analysing the association between paternal grandfather age and childhood autism. Compared with men who were 20 to 24 at their son's birth, the odds of having a grandchild with autism were:

not significantly different among those aged less than 20 years (OR 0.91, 95% CI 0.73 to 1.12)
10% higher among those aged 25 to 29 years (OR 1.00 to 1.20)
17% higher among those aged 30 to 34 years (OR 1.17, 95% CI 1.05 to 1.30)
15% higher among those aged 35 to 39 years (OR 1.15, 95% CI 1.02 to 1.31)
23% higher among those aged 40 to 44 years (OR 1.32, 95% CI 1.05 to 1.44)
60% higher among those aged 45 to 49 years (OR 1.23, 95% CI 1.30 to 1.97)
67% higher among those aged 50 years or more (OR 1.67, 95% CI 1.25 to 2.24)

How did the researchers interpret the results?

The researchers concluded that a "grandfather's age is associated with risk of childhood autism, independent of paternal or maternal age", and that their results "provide new information about the paternal age effect and its effect on future generations".

Conclusion

The large study suggests that there is an association between a grandfather's age at the birth of his daughter or son and the diagnosis of autism in his grandchild. This research raises interesting questions surrounding the genetic components of autism spectrum disorders. But the study cannot in itself explain what may underpin this relationship.

The researchers suggest several possible explanations for the links between paternal age and childhood autism. These include the association being caused by "an increase rate of mutations in the sperm of older men", or that it could be explained by other variables such as "men with mental or personality disorders being more likely to become fathers at older ages". However, this study did not test either of these possible explanations.

Previous research has suggested that a father's age when his child is born is associated with an increased risk of autism in his children. Analyses of the data used in the current study support that finding. The main analyses in this current report further suggest that a grandfather's age when his child is born is also associated with an increased risk of autism in his grandchild.

However, it's worth noting the limitations of this study. While there were a large number of cases and controls included in the data analysis, they represent only 60-63% of the original group of participants. This is a fairly high drop-out rate, and may bias the results if those whose data was not available differed from those included in the analysis in important ways.

For example, data on grandparental age may have been harder to come by for older grandparents, because older records may be incomplete. The researchers attempted to account for this by carrying out a sensitivity analysis (a statistical technique that attempts to account for uncertainty). They say the results of this analysis indicate that the association was not biased by missing data on grandparental age, but arguably this is more of an educated guess than a certainty.

The researchers conclude that, "older men should not be discouraged from having children based on these findings," an important conclusion that was also reported by the media.

These results may provide interesting insights for researchers as to the possible mechanisms behind the development of childhood autism. However, as we do not yet know what causes the conditions on the autistic spectrum, there is no need to decide whether and when to have a child based on this study.