Autism risk associated with parental age and with increasing difference in age between the parents

Abstract

Advancing paternal and maternal age have both been associated with risk for autism spectrum disorders (ASD). However, the shape of the association remains unclear, and results on the joint associations is lacking. This study tests if advancing paternal and maternal ages are independently associated with ASD risk and estimates the functional form of the associations. In a population-based cohort study from five countries (Denmark, Israel, Norway, Sweden and Western Australia) comprising 5 766 794 children born 1985–2004 and followed up to the end of 2004–2009, the relative risk (RR) of ASD was estimated by using logistic regression and splines. Our analyses included 30 902 cases of ASD. Advancing paternal and maternal age were each associated with increased RR of ASD after adjusting for confounding and the other parent's age (mothers 40–49 years vs 20–29 years, RR=1.15 (95% confidence interval (CI): 1.06–1.24), P-value<0.001; fathers⩾50 years vs 20–29 years, RR=1.66 (95% CI: 1.49–1.85), P-value<0.001). Younger maternal age was also associated with increased risk for ASD (mothers <20 years vs 20–29 years, RR=1.18 (95% CI: 1.08–1.29), P-value<0.001). There was a joint effect of maternal and paternal age with increasing risk of ASD for couples with increasing differences in parental ages. We did not find any support for a modifying effect by the sex of the offspring. In conclusion, as shown in multiple geographic regions, increases in ASD was not only limited to advancing paternal or maternal age alone but also to differences parental age including younger or older similarly aged parents as well as disparately aged parents.

Role of environmental and genetic factors in autism spectrum disorder

“…In 2015, a population-based study spanning five countries (Denmark, Israel, Norway, Sweden and Western Australia) with 57,66,794 children including 30,902 cases of ASD, researchers found that autism risk was associated with parental age and increasing age difference between parents. 16 In another study on 2,53,347 participants, researchers found that both maternal and paternal age were independently associated with autism. 15 Croen et al found that risk of ASD was increased significantly with each 10 years increase in maternal and paternal age.…”

Pharmaceuticals and Stem Cells in Autism Spectrum Disorders: Wishful Thinking?

“…Despite the myriad studies conducted on ASDs thus far, the exact etiology and pathophysiology of these disorders remain poorly understood. [12][13][14] For instance, although increasing paternal and maternal ages at birth appear to increase the risk of a child developing autism, 15 the underlying molecular processes linking this association to disease pathogenesis remain elusive. In addition, the clear heterogeneity of symptoms between affected individuals very likely reflects the heterogeneity of pathophysiological mechanisms in ASDs.…”

Aging of the Male Germline: Influence of Advanced Male Age on Reproductive Outcome

“…Austim, a mental disorder defined by restricted, repetitive forms of behavior, and substantial deficiencies in social functioning has also been related to APA. Studies have demonstrated that fathers above 40 years of age display a risk three to five times higher to experience an autism onset on their offspring than younger men [115,118,119]. Although the risk is higher when both the mother and father are of advanced age, APA is independently correlated to autism of the offspring [117,119].…”