Is advanced paternal age a health risk for the offspring?

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.