Although maternal age is clearly associated with risk for congenital malformations, the independent effects of paternal age remain unclear, mainly because of the strong correlation between maternal and paternal age. To tease out these effects, investigators in Denmark used national registries to identify 71,937 firstborn children (all singletons) of couples in which the mother was between 20 and 29 years of age and the father was at least 20.
A total of 3910 children (5.4%) were determined to have congenital malformations; fewer than one third of these malformations were diagnosed at birth, and about half were diagnosed within the first year of life. Although advancing paternal age was not related to the overall prevalence of congenital malformations, it was significantly associated with malformations of the extremities, syndromes of multiple systems, and Down syndrome. The occurrence of such malformations was about one third higher with fathers aged 40 or older than with fathers aged 20 to 29 (although the absolute increase in risk was quite small).
This study, the largest to date on the topic, raises the possibility that advanced paternal age might be associated with an increased occurrence of certain abnormalities. The authors suggest that this association might be attributable to mutations of the male gametes induced by biological or environmental factors.
Reference:
Zhu JL et al. Paternal age and congenital malformations. Hum Reprod 2005 Nov; 20:3173-7.