The Association Between Parental Age and Autism‐Related Outcomes in Children at High Familial Risk for Autism

Abstract

Advanced parental age is a well‐replicated risk factor for autism spectrum disorder (ASD), a neurodevelopmental condition with a complex and not well‐defined etiology. We sought to determine parental age associations with ASD‐related outcomes in subjects at high familial risk for ASD. A total of 397 younger siblings of a child with ASD, drawn from existing prospective high familial risk cohorts, were included in these analyses. Overall, we did not observe significant associations of advanced parental age with clinical ASD diagnosis, Social Responsiveness Scale, or Vineland Adaptive Behavior Scales scores. Instead, increased odds of ASD were found with paternal age < 30 years (adjusted odds ratio [AOR] = 2.83 and 95% confidence intervals [CI] = 1.14–7.02). Likewise, younger age (<30 years) for both parents was associated with decreases in Mullen Scales of Early Learning early learning composite (MSEL‐ELC) scores (adjusted β = −9.62, 95% CI = −17.1 to −2.15). We also found significant increases in cognitive functioning based on MSEL‐ELC scores with increasing paternal age (adjusted β associated with a 10‐year increase in paternal age = 5.51, 95% CI = 0.70–10.3). Results suggest the potential for a different relationship between parental age and ASD‐related outcomes in families with elevated ASD risk than has been observed in general population samples. Autism Res 2020, 13: 998‐1010. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary Previous work suggests that older parents have a greater likelihood of having a child with autism. We investigated this relationship in the younger siblings of families who already had a child with autism. In this setting, we found a higher likelihood of autism, as well as poorer cognitive scores, in the siblings with younger fathers, and higher cognitive scores in the siblings with older parents. These results suggest that parental age associations may differ based on children's familial risk for autism.

Individual and Environmental Factors Affecting Adaptive Behavior of Toddlers with Autism Spectrum Disorder: Role of Parents’ Socio-cultural Level

“…Previous studies found that advanced parental age is associated with an increased risk of ASD in the offspring (Wu et al 2017 ). Our study indicates that advanced parental age is not an environmental risk factor for weakened adaptive behavior in toddlers with ASD, consistent with previous studies (Ben Itzchak et al 2011 ; Lyall et al 2020 ; Vierck and Silverman 2015 ).…”

“…Regarding other environmental factors, previous investigations have explored the influence of parental sociodemographic characteristics, such as parents' age, on the adaptive behavior of children with ASD (Vierck and Silverman 2015). Several previous studies reported no statistically significant relationships between both maternal and paternal age and the adaptive behavior of their offspring with ASD (Ben Itzchak et al 2011;Lyall et al 2020;Vierck and Silverman 2015).…”

A phenotypic spectrum of autism is attributable to the combined effects of rare variants, polygenic risk and sex

“…This result is consistent with an increased susceptibility of males to rare-variant risk. Thus rare variants of large effect in fathers could explain an increased risk for ASD in the children of parents who are very young 42 . Likewise, previous reports of a U-shaped effect of father's age on risk for developmental impairments in offspring 43 may be attributable to 343 the combined effects of inhLoF, DNMs and PSEA.…”

Parental age and autism severity in the Rhode Island Consortium for Autism Research and Treatment (RI‐CART) study

“…This is only the second study to our knowledge that has utilized the ADOS in examining this association, with one prior study finding no differences in ADOS symptom severity score between older (34+) and younger (<34) parents at the child's birth ( n = 529) (Ben Itzchak et al, 2011). When using parent‐report measures, ASD severity correlated with paternal age (but not maternal age) in one ASD sample (Rieske & Matson, 2019), but did not correlate with parental age in a sample of siblings of children with ASD (Lyall et al, 2020). The magnitude of the association in the current study was statistically significant, yet objectively small, and thus inconsistencies in prior findings may be due to issues of statistical power.…”