Is advanced paternal age a health risk for the offspring?

Abstract

In this article we review the epidemiologic evidence for adverse health effects in offspring of fathers of advanced age. First the evidence regarding fetal survival is addressed, and afterward we review the evidence regarding morbidity in children with older fathers. The adverse conditions most consistently associated with increased paternal age are stillbirths, musculo-skeletal syndromes, cleft palate, acute lymphoblastic leukemia and retinoblastoma, and neurodevelopmental disorders in the autism spectrum and schizophrenia. Finally, we consider the public health impact of the increasing paternal age. We conclude that the adverse health effects in children that might be caused by the present increase in paternal age are severe but quantitatively of minor importance. However, identification of morbidities that are more frequent in offspring of older fathers, after having taken any maternal age effects and other confounding into account, may lead to a better understanding of the pathogenesis behind such conditions.

Paternal factors in preconception care: the case of paternal age

“…With the growing understanding of the importance of contributions by men to perinatal health, however, preconception health is increasingly being defined as the health of all people of reproductive age, regardless of sex 13. A key component of preconception health is having a reproductive life plan—defined by the US Centers for Disease Control and Prevention as a plan for “a person’s intentions regarding the number and timing of pregnancies in the context of their personal values and life goals.”14 Given that many couples might not be aware of the potential impact of paternal age on perinatal health, the current findings underscore the importance of including, in reproductive life plans, discussions of paternal age and declines in sperm quality, and other risk factors such as chronic disease, that are related to age 9. Currently, the best method for engaging men in preconception care remains elusive 13.…”

“…These factors have also been linked to adverse perinatal outcomes 9. Therefore, although the observed association between paternal age and adverse perinatal outcomes could be real, it might not be causal 9. As described by previous authors, age is both a “biological fact” and a “social construct,”9 and the reasons for delaying childbearing—and their potential influences on perinatal outcomes—should be acknowledged.…”

“…Studies have shown that advanced paternal age is associated with negative health behaviours such as smoking and frequent alcohol consumption, obesity, chronic disease, mental illness, and subfertility 8910. These factors have also been linked to adverse perinatal outcomes 9. Therefore, although the observed association between paternal age and adverse perinatal outcomes could be real, it might not be causal 9.…”

“…The authors estimated that as much as 18% of adverse perinatal outcomes over the past decade could be attributable to an increase in fathers aged 45 or older 7. However, since population attributable risk is driven not only by the strength of the association between exposure and outcome but also by the exposure’s prevalence,11 the importance of advanced paternal age at a population level would be expected to increase as its prevalence continues to rise 9. Whether driven by biological or selection factors, the impact warrants attention.…”

Disease burden in offspring is associated with changing paternal demographics in the United States

“…Several reports have shown that advanced paternal age is associated with an increased risk of certain cancers and neuropsychiatric diseases in offspring (D'Onofrio et al ., ; Ramasamy et al ., ; Urhoj et al ., ; Frans et al ., ). Nevertheless, the number of expected attributable cases of disease due to older fathers has yet to be determined (Nybo Andersen & Urhoj, ).…”