Researchers who studied records of all births occurring in California in the 1990s found that the risk of having a child with autism was significantly higher when the mother was older, regardless of the father's age, except when the mother was younger, the risk was also higher if the father were older.

The study was the work of researchers from the University of California (UC), Davis, and you can read about in a report published in the 8 February Early View issue of the journal Autism Research.

Autism is a pervasive development disorder that affects between 1 in 100 and 1 in 110 children in the US, said the researchers. It starts before the age of 3 and is characterized by repetitive and restricted behaviors and deficiency in social skills and communication and is thought to be linked to abnormal brain development that probably starts in the womb.

Other studies have shown that the older the parents, the higher the risk of having a child with autism, but the results tend to be contradictory when it comes to deciding whether it is the age of the mother or the age of the father that most contributes to the risk. For example one study concluded that when the father was over 40 the risk of having a child with autism was six times higher than when the father was under 30.

Lead and corresponding author Janie Shelton, a doctoral student in the UC Davis Department of Public Health Sciences, told the media that:

"This study challenges a current theory in autism epidemiology that identifies the father's age as a key factor in increasing the risk of having a child with autism."

"It shows that while maternal age consistently increases the risk of autism, the father's age only contributes an increased risk when the father is older and the mother is under 30 years old," she added, explaining that:

"Among mothers over 30, increases in the father's age do not appear to further increase the risk of autism."

For the study, Shelton and colleagues examined the electronic records for all births in California from 1 January 1990 to 31 December 1999 and then extracted from the California Department of Developmental Services records cases of autism in children born in that period. They defined a case of autism as a diagnosis of full-syndrome autism registered at a California Regional Center. From the detailed information in the birth records they were also able to find out the ages and levels of education of both parents.

A small number of records did not contain parental age and level of education, so the researchers excluded them from the analysis, and they also analysed cases of multiple births separately from singletons.

Taking all these exclusions into account, the total size of the study sample was in the region of 4.9 million births and 12,159 cases of autism, making it one of the largest population-based studies to quantify how each parent's age -- separately and together-- affects the risk of having a child with autism.

After analysing the data using a statistical method called multivariate logistic regression the researchers found that:
  • The risk of having a child with autism went up in step with advancing maternal age regardless of the age of the father.

  • The risk of having a child with autism went up by 18 per cent (nearly one fifth) for every 5 years of increase in the mother's age.

  • Compared with mothers aged between 25 and 29, the risk of a mother aged 40 and over having a child with autism was 51 per cent higher (adjusted odds ratio, aOR, 1.51, 95 per cent confidence interval, CI, ranged from 1.35 to 1.71).

  • Compared to mothers under 25 years of age this figure was 77 per cent (aOR 1.77, 95 per cent CI 1.56 to 2.00).

  • In contrast, risk of autism was linked to advanced paternal age primarily when the mother was under 30.

  • For mothers under 30, the risk of autism when fathers were over 40 was 59 per cent higher compared to fathers aged 25 to 29 (aOR 1.59, 95 per cent CI 1.37 to 1.85).

  • However, this figure changed dramatically once the mother's age went over 30 such that the risk of autism due to father's age dropped to 13 per cent when the father was over 40 (compared to 25 - 29 year old fathers).
Shelton and colleagues concluded that based on these results it would appear that:

"Women's risk for delivering a child who develops autism increases throughout their reproductive years whereas father's age confers increased risk for autism when mothers are <30, but has little effect when mothers are past age 30."

"We also calculated that the recent trend towards delayed childbearing contributed approximately a 4.6% increase in autism diagnoses in California over the decade," they added.

In California during the 1990s, the number of women who gave birth when they were over 40 went up by more than 300 per cent, while the number of cases of autism went up by 600 per cent. This study suggests that only a tiny fraction of the 6-fold increase in autism cases in the 1990s can be put down to women waiting longer to have children.

One of the advantages of the large study size was that the researchers were able to explore the interaction between the parental ages and the risk of autism: they could hold one parent's age constant while they explored the link with the other parent's age. They wrote that this methodology is more effective and requires fewer assumptions than the models used in earlier studies.

Understanding the intricacies of the relationship between parental age and risk of autism is crucial if we are to shed light on its biological causes.

Other studies have already shown that the older the mother the higher the risk for a range of conditions including loss of the baby, infertility, low birth-weight, congential abnormalities and genetic defects.

Senior author Dr Irva Hertz-Picciotto, professor of public health sciences at UC Davis and also a researcher at the UC Davis MIND Institute, said that we don't know what the biological explanation is for why having an older parent increases the risk of a child having autism.

"We still need to figure out what it is about older parents that puts their children at greater risk for autism and other adverse outcomes, so that we can begin to design interventions," she said.

However, one UC Davis study published in 2008 suggested a clue: in the cohort they studied they found that some mothers of children with autism had antibodies to fetal brain protein, while none of the mothers of the children without autism did.

Getting older tends to increase autoantibody production, so further studies into this might be useful said the authors, adding that as we get older we also tend to accumulate more chemicals from the environment in our bodies, and this could be another mechanism that influences the parental age effect.

The authors also suggested epigenetics could be a factor. Epigenetics is still an emerging field and there is some confusion about exactly what the term means, but essentially it reflects the likelihood that it is not our DNA per se that decides what happens in our cells and bodies but how the "map" is interpreted and this changes as we get older, such that, as the authors suggested, an older parent may transfer a "multitude of molecular functional alterations to a child".

"Thus epigenetics may be involved in the risks contributed by advancing parental age as a result of changes induced by stresses from environmental chemicals, co-morbidity or assistive reproductive therapy," they added.

"Independent and dependent contributions of advanced maternal and paternal ages to autism risk."
Janie F. Shelton, Daniel J. Tancredi, Irva Hertz-Picciotto.
Autism Research, Early View, Published online 8 February 2010.
DOI:10.1002/aur.116

Source: UC Davis MIND.

Written by: Catharine Paddock, PhD