“First-born children of older parents are more likely to be autistic,” warned The Daily Telegraph. It reported on a study that examined the medical records of 240,000 children born in the US in 1994, and found that both maternal and paternal age were independently associated with autism. It said mothers aged 35 or older had a 30% higher chance of having an autistic child compared to mothers aged 25 to 29, while Fathers over 40 years had a 40% higher risk than those aged 25 to 29.

The study quoted in this news piece was not limited to autism but looked at the broader condition of autistic spectrum disorder (ASD). The study’s limitations mean that a definitive conclusion cannot be drawn about the contribution of parental age to overall risk for ASD. Its cause is still largely unknown, and it is unlikely that one factor alone will be responsible. The researchers themselves say that large long-term studies of well-characterised birth cohorts are needed to confirm these findings.

Where did the story come from?

Dr Maureen Durkin and colleagues from the University of Wisconsin School of Medicine and Public Health carried out this study. The work was funded by the Center for Disease Control and Prevention in Atlanta. The study was published in the peer-reviewed medical journal, American Journal of Epidemiology.

What kind of scientific study was this?

In this case-cohort study, the researchers were interested in the effects of parental age on the risk of autism spectrum disorder in the offspring. In this sort of study, both cases and controls come from the same cohort (population group).

The population comprised all 253,347 live births that took place in 1994 to women living in 10 areas around the US, (including Alabama, Arizona, Arkansas, Colorado, Georgia, Maryland, Missouri, New Jersey, North Carolina and Wisconsin). Information on these births was obtained from birth records held at the Wisconsin Department of Health and Family Services, and birth data from the National Center for Health Statistics. The records included information on the age of the mother and father, birth order, and other important variables.

From this population, the researchers identified children who had been diagnosed with autism in 2002 (at age eight) using the Autism and Developmental Disabilities Monitoring Network. This gave a total of 2,142 children with a ‘diagnosis’ of autistic spectrum disorder [ASD], namely autistic disorder, pervasive developmental disorder not otherwise specified, or Asperger’s syndrome.

Birth certificate information and information on birth order and parental age was only available for 1,251 of the children diagnosed with autism (58% of the total number of cases), so only these children were used in analysis as the ‘cases’. A ‘diagnosis’ was made if there was documented classification of a disorder, or if there was evidence from a medical or educational setting that indicated ‘unusual behaviours consistent with ASD’.

The researchers then assessed whether the age of the child’s parents had any effect on whether they went on to develop an autistic spectrum disorder. They took into account (i.e. adjusted for) other factors such as gender, gestational age, birth weight, multiple birth, maternal ethnicity, education and site of recruitment.

What were the results of the study?

The researchers found a link between increasing parental age and odds of ‘diagnosis’ of autistic spectrum disorder by age eight. First-born children to mothers aged 35 years and over who also had fathers aged 40 years and over were at the greatest risk of autism (triple the likelihood). This was compared with children who were third or more in order of birth to younger parents (mother aged 20-34 years and father younger than 40 years). In separate analyses, there were generally “modest” links between autism and other parental age groups and other birth orders, ranging from 1.4 times as likely to 2.3 times.

What interpretations did the researchers draw from these results?

The researchers conclude that these results provide the “most compelling evidence to date that autistic spectrum disorder risk is linked to both maternal and paternal age, and decreases with birth order”. They say that the increased risk of autism with both maternal and paternal age has implications for public health planning.

What does the NHS Knowledge Service make of this study?

This case-cohort study concluded that there is a link between maternal and paternal age and risk of developing autistic spectrum disorder. In a study of this design, it is important to measure and adjust for other factors that may be responsible for the link. Here, the researchers have adjusted for a number of these factors, but they note that they did not adjust for infertility treatments and psychopathology or behavioural traits of parents. The researchers also note that their study cannot control for the fact that older parents may have more knowledge of developmental disorders and therefore be more likely to seek a diagnosis for their child. Therefore, it is possible that the different numbers of autistic children diagnosed to parents of different ages may be a result of this different rate of diagnosis.

The researchers identify other shortcomings of their study, saying that measures of parity (numbers of children) only relates to mothers and does not account for other children of the fathers in the cohort. They also say that other confounders may not have been measured, including possible misclassification of ASD, and an inability to adjust for paternal education due to missing information.

Importantly, the study assessed the link between parental age and autistic spectrum disorders, and this includes a wide range of conditions, including typical autism. However, the researchers note that 80% of the ASD cases were autistic disorder, and among the remaining 20% they could not differentiate between autism, PDD-NOS and Asperger’s. The ‘diagnosis’ of ASD was not necessarily reliant on a clinical process, and the researchers relied on school or medical evaluations to determine the diagnosis themselves in 35% of the participating children. The accuracy of this process is questionable.

Another important point is that only 58% of the actual ‘cases’ were included in the analyses because of missing information from birth certificates, maternal or paternal age and birth order. Although the researchers state that their final sample was comparable to the total population of ASD cases regarding demographic factors and ASD case characteristics, differences in the factors being measured between the children who were included and those who were excluded would have biased the results. The researchers have considered this however, and say that the exclusion for missing information applied to both ‘cases’ and the comparison cohort, so it is unlikely to have affected the cases differently.

What causes ASD is largely unknown, but it is likely that several factors are responsible. The study has too many limitations for a definitive conclusion to be drawn about the contribution of parental age to overall risk for ASD. As the researchers say, large long-term studies of well-characterised birth cohorts are needed to confirm these findings.