Parental age and the risk of autism spectrum disorders: findings from a Swedish population-based cohort

Methods: The sample consisted of 417 303 Swedish children born 1984-2003. ASD case status (N = 4746) was ascertained using national and regional registers. Smoothing splines in generalized additive models were used to estimate associations of parental age with ASD. Results: Whereas advancing parental age increased the risk of child ASD, maternal age effects were non-linear and paternal age effects were linear. Compared with mothers at the median age 29 years, those < 29 had similar risk, whereas risk increased after age 30, with an odds ratio (OR) of 1.75 [95% (CI): 1.63-1.89] at ages 40-45. For fathers, compared with the median age of 32 years, the OR for ages 55-59 was 1.39 (1.29-1.50). The risk of ASD was greater for older mothers as compared with older fathers. For example, mothers aged 40-45 (epsilon 97.2th percentile) had an estimated 18.63 (95% CI: 17.25-20.01) ASD cases per 1000 births, whereas fathers aged 55-59 (epsilon 99.7th percentile) had 16.35 (95% CI: 15.11-17.58) ASD cases per 1000 births. In analyses stratified by co-parental age, increased risk due to advancing paternal age was evident only with mothers 35 years. In contrast, advancing maternal age increased risk regardless of paternal age. Advancing parental age was more strongly associated with ASD with ID, compared with ASD without ID. Conclusions: We confirm prior findings that advancing parental age increases risk of ASD, particularly for ASD with ID, in a manner dependent on co-parental age. Although recent attention has emphasized the effects of older fathers on ASD risk, an increase of n years in maternal age has greater implications for ASD risk than a similar increase in paternal age.