Older fathers and morbidity in their offspring: what’s new ?

Around sixty years ago an article was published in the Lancet demonstrating, for the first time, a link between advancing paternal age and the increased risk of a birth defect in their offspring, namely achondroplasia. In spite of the fact that in the six decades since then there have been numerous studies showing similar associations between the age of fathers and a variety of birth defects, relevant textbooks usually fail to mention these findings and until recently the popular press has resolutely ignored the topic. So while healthcare workers and indeed prospective parents are very much aware of the increased risk of morbidity in the infants of older expectant mothers, most remain blissfully ignorant of potential problems linked to advanced paternal age.
The most robust studies in the field have been carried out in the Nordic countries, where the age of prospective fathers has long been included in antenatal records. Advanced paternal age has been correlated with Down syndrome, as well as with many conditions resulting from autosomal dominant mutations, such as Apert syndrome, Marfan’s syndrome, osteogenesis imperfecta and neurofibromatosis. The risk of several common conditions with less straightforward inheritance patterns, such as cleft palate, increases with paternal age. Advanced paternal age has been correlated with an increased risk of recessive mutations on the X chromosome of female offspring as well. Data on sex-linked conditions such as Duchenne muscular dystrophy and hemophilia in male grandchildren have allowed this association to be demonstrated; presumably recessive autosomal mutations are also more common in the children of older fathers. Several recent studies have now linked increased paternal age at their children’s births with risk of neuropsychiatric disorders in the offspring. A very robust Danish population-based study that followed the health records of nearly 3 million individuals from birth found an increased risk of schizophrenia, mental retardation and autism in the offspring of older fathers. A Swedish/American population study of 2.6 million individuals concluded that increased genetic mutations during spermatogenesis in older men increased the risk of attention-deficit hyperactivity disorder, psychosis and bipolar disorder as well as autism in their offspring.
Such population studies are complex and their analysis can always be criticised, but surely we should not, yet again, try to sweep these results under the carpet, particularly since the trend in the West is towards delayed parenthood. Healthcare workers should be made aware of the increased risks to the offspring of older fathers as well as mothers, and relevant information should be disseminated so that older men are not lulled into reproductive irresponsibility.