The influence of paternal age on Down syndrome

Purpose: Children born to older parents are at greater risk for genetic abnormalities, such as Down syndrome. The influence of maternal age on Down syndrome is well established but little is known about the genetic consequences of advanced paternal age. Materials and Methods: Data on the incidence of Down syndrome from 1983 to 1997 (3,419 cases) were obtained from the New York State Department of Health congenital malformations registry. Parental age was modeled as individual age groups and by a single linear covariate (drift model). The log linear chi-square test and a test of significance of different explanatory variables were used to evaluate these models to determine significance. We compared actual Down syndrome rates by maternal age with the estimated rate corrected for paternal age. Results: From 1983 to 1997 a dramatic increase in the number of infants born to parents 35 years or older was observed. During the 15-year study period there was an increase of 111% and 60% in the number of mothers and fathers 35 years old or older, respectively. There was no parental age influence on Down syndrome until age 35 years and older. A paternal age effect was seen in association with a maternal age of 35 years and older, and it was most pronounced when maternal age was 40 years and older (p = 0.0004). In this later maternal age group the paternal contribution to Down syndrome was 50%. Conclusions: Advanced paternal age combined with maternal age significantly influences the incidence of Down syndrome. This effect may represent a paradigm for other genetic abnormalities in children of older fathers.