Parental Age and Differential Estimates of Risk for Neuropsychiatric Disorders: Findings From the Danish Birth Cohort

Abstract

Objective: Parental age at birth has been shown to affect the rates of a range of neurodevelopmental disorders, but the understanding of the mechanisms through which it mediates different outcomes is still lacking. We used a population-based cohort to assess differential effects of parental age on estimates of risk across pediatric-onset neuropsychiatric disorders: autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD) and Tourette syndrome/chronic tic disorder (TS/CT). Method: Our study cohort included all singleton births in Denmark between 1980 and 2007 with full information on parental ages (N=1,490,745), followed through December 31, 2013. Cases of ASD, ADHD, OCD and TS/CT were identified in the Danish Psychiatric Central Register and the National Patient Register. Associations with parental age were modeled using a stratified Cox regression, allowing for changes in baseline diagnostic rates across time. Results: Younger parental age was significantly associated with increased estimates of risk for ADHD and TS/CT, while older parental age was associated with ASD and OCD. Except for OCD, we did not observe any evidence for differential effects of parental ages on male vs. female offspring. Conclusion: We provide novel evidence for the association between age at parenthood and TS/CT and OCD, and show for the first time in a population-based sample that parental age confers differential risk rates for pediatric-onset psychiatric disorders. Our results are consistent with a model of both shared and unshared risk architecture for pediatric-onset neuropsychiatric conditions, highlighting unique contributions of maternal and paternal ages.

Parental Age in Relation to Offspring’s Neurodevelopment

“…Mikkelsen et al (2016) found in a population-based sample (N = 943,785) that offspring of mothers who gave birth to children early in their reproductive lives were more vulnerable to develop ADHD. This same outcome was also observed in a casecontrol (N = 10,409; N = 39,125) study by Chudal et al (2015) and in population-based cohort studies (N = 1,495,543; N = 1,490,745) by Chang et al (2014) and Janecka et al (2019). The results are more diverse for fathers; while Mikkelsen et al (2016) found no effect for fathers ' age, D'Onofrio et al (2014) reported in a population-based study (N = 2,615,081) that offspring of fathers 45 years and older were at higher risk for ADHD.…”

“…Alternatively, SES could affect at what age offspring is born, which in turn influences offspring outcome. In that case, adjusting for SES could introduce bias (Janecka et al, 2019). Hence, we conclude that older parents tend to have offspring with fewer attention problems, higher IQ, and educational achievement, but for fathers the associations are small and mostly explained by higher SES.…”

“…for offspring on a psychosocial or contextual level improving neurocognitive functioning (Janecka et al, 2019;Noble et al, 2007). Parents who postpone parenthood are typically highly educated with higher incomes at the time they start a family.…”

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

“…We also observed significantly decreased MSEL scores when both parents were younger (under the age of 30). As noted, a number of studies have suggested that young parental age may also increase risk of adverse neurodevelopmental outcomes [Janecka et al, 2019;Lundstrom et al, 2010;Merikangas et al, 2017]. Liabilities associated with younger age at childbearing [Chen et al, 2008;Lundstrom et al, 2010] (see also below) may also influence risk of adverse cognitive development.…”

“…Beyond the well-documented associations with chromosomal disorders like Down syndrome, parental age has also been associated with other conditions with relevance to ASD [de Kluiver, Buizer-Voskamp, Dolan, & Boomsma, 2017;McGrath et al, 2014], though patterns of associations may differ. For example, studies have reported a nonlinear association between paternal age and offspring verbal IQ [Gajos & Beaver, 2017], increased risk of child intellectual disability with younger mothers [McGrath et al, 2014], and increased risk of attention deficit hyperactivity disorder and Tourette's/chronic tic disorder with younger parents [Janecka et al, 2019]. Prior work examining associations with quantitatively measured ASD-related traits is limited.…”