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

Kristen Lyall; Lanxin Song; Kelly Botteron; Lisa A Croen; Stephen R Dager; M Daniele Fallin; Heather C Hazlett; Elizabeth Kauffman; Rebecca Landa; Christine Ladd-Acosta; Daniel S Messinger; Sally Ozonoff; Juhi Pandey; Joseph Piven; Rebecca J Schmidt; Robert T Schultz; Wendy L Stone; Craig J Newschaffer; Heather E Volk

doi:10.1002/aur.2303

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

Autism Res. 2020 Jun;13(6):998-1010. doi: 10.1002/aur.2303. Epub 2020 Apr 21.

Authors

Kristen Lyall¹, Lanxin Song², Kelly Botteron³, Lisa A Croen⁴, Stephen R Dager⁵, M Daniele Fallin², Heather C Hazlett⁶, Elizabeth Kauffman¹, Rebecca Landa⁷, Christine Ladd-Acosta⁸, Daniel S Messinger⁹, Sally Ozonoff¹⁰, Juhi Pandey¹¹, Joseph Piven⁶, Rebecca J Schmidt^{12

13}, Robert T Schultz¹¹, Wendy L Stone¹⁴, Craig J Newschaffer¹⁵, Heather E Volk²

Affiliations

¹ AJ Drexel Autism Institute, Drexel University, Philadelphia, Pennsylvania, USA.
² Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
³ Department of Psychiatry, Washington University, St Louis, Missouri, USA.
⁴ Kaiser Permanente Division of Research, Oakland, California, USA.
⁵ Department of Radiology, University of Washington, Seattle, Washington, USA.
⁶ Department of Psychiatry, University of North Carolina, Chapel Hill, North Carolina, USA.
⁷ Department of Psychiatry and Behavioral Sciences, Center for Autism and Related Disorders, Kennedy Krieger Institute, Johns Hopkins University, Baltimore, Maryland, USA.
⁸ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
⁹ Department of Psychology, University of Miami, Miami, Florida, USA.
¹⁰ MIND Institute, Department of Psychiatry and Behavioral Sciences, University of California Davis, Sacramento, California, USA.
¹¹ Center for Autism Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
¹² Department of Public Health, University of California Davis, Davis, California, USA.
¹³ MIND Institute, University of California Davis, Sacramento, California, USA.
¹⁴ Department of Psychology, University of Washington, Seattle, Washington, USA.
¹⁵ College of Health and Human Development, Pennsylvania State University, State College, Pennsylvania, USA.

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.

Keywords: autism; autism-related traits; high familial risk; parental age.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adult
Autism Spectrum Disorder / epidemiology*
Autism Spectrum Disorder / genetics*
Autistic Disorder / epidemiology
Autistic Disorder / genetics
Child, Preschool
Female
Genetic Predisposition to Disease*
Humans
Infant
Male
Maternal Age*
Paternal Age*
Prospective Studies

Abstract

Publication types

MeSH terms

Grants and funding