Advanced Parental Age and the Risk of Autism Spectrum Disorder

Abstract

This study evaluated independent effects of maternal and paternal age on risk of autism spectrum disorder. A case-cohort design was implemented using data from 10 US study sites participating in the Centers for Disease Control and Prevention's Autism and Developmental Disabilities Monitoring Network. The 1994 birth cohort included 253,347 study-site births with complete parental age information. Cases included 1,251 children aged 8 years with complete parental age information from the same birth cohort and identified as having an autism spectrum disorder based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. After adjustment for the other parent's age, birth order, maternal education, and other covariates, both maternal and paternal age were independently associated with autism (adjusted odds ratio for maternal age ≥35 vs. 25–29 years = 1.3, 95% confidence interval: 1.1, 1.6; adjusted odds ratio for paternal age ≥40 years vs. 25–29 years = 1.4, 95% confidence interval: 1.1, 1.8). Firstborn offspring of 2 older parents were 3 times more likely to develop autism than were third- or later-born offspring of mothers aged 20–34 years and fathers aged <40 years (odds ratio = 3.1, 95% confidence interval: 2.0, 4.7). The increase in autism risk with both maternal and paternal age has potential implications for public health planning and investigations of autism etiology.

Advancing paternal age and risk of autism: new evidence from a population-based study and a meta-analysis of epidemiological studies

“…Weighted odds ratios (ORs) and 95% CIs were calculated. Three sensitivity analyses were conducted including the removal of studies with (a) the largest magnitude of association; (b) that included autism and high rates of autism spectrum disorders (6,7,36); and (c), high rates of missing data on paternal age (6,8,13).…”

“…Second, to carefully test the possibility that the paternal age effect pertains only to first born children, and consideration of whether 'stoppage' (i.e., after recognizing that a child has a neurodevelopmental problem stopping having subsequent children) might create an artefact of increased likelihood that a child with autism from an older father will also have a low birth order (6). Third, to addresses the hypothesis that fathers of autistic individuals delay paternity because of traits associated with the autism phenotype.…”

“…Several studies report a strong association (6)(7)(8)(9)(10), yet others do not (11)(12)(13). The association may be unclear due to methodological limitations.…”

The association between the interpregnancy interval and autism spectrum disorder in a Canadian cohort

“…6,7 Separate logistic regression models were fit for each case group to estimate crude and adjusted odds ratios (ORs) for ASD in the second-born children, using the same comparison group in each model. A priori, we decided to include the following covariates in the models due to previously documented associations with ASD: child's sex, birth year (we mean-centered this variable and created a quadratic term to account for birth year's non-linear association with ASD in our cohort), and presence of an intellectual disability (defined as a "Multiple Handicaps" special needs code in the Education data, or the presence of various diagnostic codes in the Medical Services or Hospital Discharge Abstracts databases 18 ), as well as maternal age at delivery (<30, 30-34, ≥35 years [19][20][21] ) and whether the mother had ever received income assistance. In a supplementary analysis, we added product terms to the regression models to explore whether certain factors interacted with the IPI to modify the association.…”

Autism Spectrum Disorders and Communication Disorders: Influences of Advanced Parental Age and Use of Assisted Reproductive Technology

“…Studies suggest that parental age at the time of conception or birth increases the risk of a child being diagnosed with ASD and other communication and neurodevelopmental disorders (e.g., Croen et al 2007;Durkin et al 2008;Frans et al 2013;Grether et al 2009;Hultman et al 2011;King et al 2009;Lundstrom et al 2010;Merikangas et al 2016;Reichenberg et al 2006;Sandin et al 2012Sandin et al , 2016Saha et al 2009;van Balkom et al 2012;Weiser et al 2008). In particular, advanced paternal age has been implicated in a higher risk of having a child with ASD (e.g., Shimada et al 2012), and both younger and older mothers have an increased risk for having a child with a CD (Silva et al 2013).…”