Advanced paternal age and risk of fetal death: a cohort study.

A possible detrimental paternal age effect on offspring health due to mutations of paternal origin should be reflected in an association between paternal age and fetal loss. The authors used data from a prospective study of 23,821 pregnant women recruited consecutively to the Danish National Birth Cohort from 1997 to 1999 to assess the association between paternal age and fetal death. Fathers of the pregnancies were identified by record linkage to population registers. The paternal age-related risks of fetal death and its components, early and late fetal loss, were estimated using survival analysis. Pregnancies fathered by a man aged 50 or more years (n = 124) had almost twice the risk of ending in a fetal loss compared with pregnancies with younger fathers (hazard ratio = 1.88, 95% confidence interval: 0.93, 3.82), after adjustment for maternal age, reproductive history, and maternal lifestyle during pregnancy. Various approaches to adjustment for potential residual confounding of the relation by maternal age did not affect the relative risk estimates. The paternal age-related risk of late fetal death was higher than the risk of early fetal death and started to increase from the age of 45 years. It should, however, be interpreted cautiously because of the restricted number of fetal deaths.