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

Sukanta Saha,Darryl W Eyles,Claire Foldi,Stephen L Buka,John J Mcgrath,Thomas H Burne,Adrian G Barnett,Carol Brayne

doi:10.1371/journal.pmed.1000040

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.

Highlights

In recent decades there has been increased attention to health outcomes in the offspring of older fathers
Evidence shows that advanced paternal age (APA) is associated with an increased risk of a wide range of disorders [1]
The aim of the present study was to explore the association between paternal age and a range of neurocognitive measures using a large, prospective birth cohort: the US-based Collaborative Perinatal Project (CPP)

Summary

Introduction

In recent decades there has been increased attention to health outcomes in the offspring of older fathers. Evidence shows that advanced paternal age (APA) is associated with an increased risk of a wide range of disorders [1]. After puberty, progenitor sperm stem cells undergo mitotic cell division once every 16 d. Advanced 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. Many men can father children throughout their lives, and little attention has been paid to the effects of older fatherhood. A woman’s eggs are formed largely while she is herself in the womb, but spermmaking cells divide throughout a man’s lifetime, increasing the chance of mutations in sperm

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