Advanced Paternal Age Is Associated with Impaired Neurocognitive Outcomes during Infancy and Childhood

Abstract

BackgroundAdvanced paternal age (APA) is associated with an increased risk of neurodevelopmental disorders such as autism and schizophrenia, as well as with dyslexia and reduced intelligence. The aim of this study was to examine the relationship between paternal age and performance on neurocognitive measures during infancy and childhood.Methods and FindingsA sample of singleton children (n = 33,437) was drawn from the US Collaborative Perinatal Project. The outcome measures were assessed at 8 mo, 4 y, and 7 y (Bayley scales, Stanford Binet Intelligence Scale, Graham-Ernhart Block Sort Test, Wechsler Intelligence Scale for Children, Wide Range Achievement Test). The main analyses examined the relationship between neurocognitive measures and paternal or maternal age when adjusted for potential confounding factors. Advanced paternal age showed significant associations with poorer scores on all of the neurocognitive measures apart from the Bayley Motor score. The findings were broadly consistent in direction and effect size at all three ages. In contrast, advanced maternal age was generally associated with better scores on these same measures.ConclusionsThe offspring of older fathers show subtle impairments on tests of neurocognitive ability during infancy and childhood. In light of secular trends related to delayed fatherhood, the clinical implications and the mechanisms underlying these findings warrant closer scrutiny.

Paternal age and reproduction

“…Nonetheless, children of older fathers are not only more likely to have several diseases of clear genetic cause (Kühnert and Nieschlag, 2004;Lambert et al, 2006), they show also an increased risk for multifactorial diseases such as birth defects (Olshan et al, 1994;McIntosh et al, 1995;Kazaura et al, 2004;Bille et al, 2005;Zhu et al, 2005a, b;Archer et al, 2007;Yang et al, 2007), childhood cancers (Moll et al, 1996;Hemminki et al, 1999;Sharpe et al, 1999;Murray et al, 2002;Yip et al, 2006), prostate cancer (Zhang et al, 1999), breast cancer (controversial) (Colditz et al, 1991;Choi et al, 2005), diabetes mellitus type l (Bingley et al, 2000;Cardwell et al, 2005), multiple sclerosis (Montgomery et al, 2004), some forms of cerebral palsy (Fletcher and Foley, 1993), schizophrenia (Malaspina, 2001), bipolar disorder (Frans et al, 2008), autism (Reichenberg et al, 2006), epilepsy (Vestergaard et al, 2005), Alzheimer disease (Whalley et al, 1995) and lower intelligence quotients (Malaspina et al, 2005;Saha et al, 2009). However, some of the reported associations need to be considered with caution for methodological reasons in the statistical analysis, especially in regard to the validity of the data sources (Kirby, 2007) (Fig.…”

Explanations for Elevated Psychiatric Vulnerability in Nonheterosexuals: Environmental Stressors, Genetics, and the HPA and HPG Axes

“…However, traits affected by mutation load are also expected to be associated with advanced paternal age, since the sperm of older men carry more de novo mutations (Crow 2000). Accordingly, advanced paternal age has been associated with higher risk of autism, bipolar, schizophrenia, and lower IQ (Auroux et al 1989;Malaspina et al 2001;Reichenberg et al 2006;Frans et al 2008;Saha et al 2009). In contrast, paternal (or maternal) age appears to h a v e n o e f f e c t o n e i t h e r s e x u a l o r i e n t a t i o n or depression (Zietsch et al in press).…”

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).…”