Down syndrome and paternal age, a new analysis of case–control data collected in the 1960s

There has been a long-running debate about the association between paternal age and Down syndrome. Some studies have failed to adequately control for maternal age, and have suffered from high levels of missing paternal age, raising concerns over selection bias. This paper analyzes an anonymously case-controlled dataset with 98% complete parental age data, originally collected to investigate the association between parental exposure to radiation and Down syndrome. In our methods the cases and controls were matched on maternal age to within 6 months, and conditional logistic regression was used to estimate the odds ratio associated with a 10-year increase in paternal age. Our results showed the estimated odds ratio for a Down syndrome pregnancy associated with a 10-year increase in paternal age was 1.13, 95%CI (0.85, 1.52). There was no statistically significant evidence of an association between paternal age and Down syndrome, but the estimated association was positive. The size of the estimated effect is much smaller than the effect of maternal age.