Intrauterine growth retardation as an endpoint in mutation epidemiology: an evaluation based on paternal age.

Czeizel recently suggested that intrauterine growth retardation might be of value as a phenotypic endpoint in mutation epidemiology. We hypothesized that if some fraction of small-for-gestational age (SGA) births are due to new germinal mutations, then an association with advanced paternal age should be present. We evaluated the relation between paternal age and SGA, low birthweight, and preterm births using a large sample of births (n = 254,892) from North Carolina. The analyses were restricted to births of mothers aged 20-34 years and adjusted for maternal age, race, education, marital status, gravidity, and smoking. No material increase in the risk of SGA, low birthweight, and preterm delivery was found for fathers in any age category. For example, odds ratios for SGA ranged from 0.87 (fathers aged 50 years or greater) to 1.13 (fathers aged 45-49 years). The results indicate no discernable relationship between SGA and related endpoints and the increase in increase of mutations that accompany advanced paternal age.