Paternal age and the risk of birth defects in offspring

Previous studies have shown that advanced paternal age is associated with an increase in new dominant mutations that may result in some rare congenital anomalies or syndromes in the offspring. Nevertheless, few epidemiologic studies have evaluated the effect of paternal age on the risk of more common birth defects. We examined data from the British Columbia Health Surveillance Registry, which included a total of 9,660 cases of birth defects (22 specific defect groups). We chose matched controls from the birth files of British Columbia (1952-1973). With the exception of an unusual change in direction in the 45-49 years age category, we found a general pattern of increasing relative risk estimates (adjusted for maternal age and other factors) with increasing paternal age for neural tube defects, congenital cataracts, reduction defects of the upper limb, and Down syndrome. For example, the adjusted relative risk estimates for neural tube defects in the offspring were 1.2 (for fathers age 30-34 years relative to 25-29 years); 1.3 (35-39); 1.6 (40-44); 0.6 (45-49); and 2.3 (men 50 years and older). Men under 20 years of age were also at increased risk for fathering children with birth defects such as neural tube defects, hypospadias, cystic kidney, and Down syndrome. We hypothesize that among certain commonly observed birth defects a subgroup of cases may be due to new, unrecognized dominant mutations.