Risk of birth abnormalities in the offspring of men with a history of cancer: a cohort study using Danish and Swedish national registries

The potential mutagenic effects of cancer therapies and the growing number of young male cancer survivors have given rise to concern about the health of their offspring. We identified all singleton children born alive in Denmark between 1994 and 2004 and in Sweden between 1994 and 2005 (n = 1,777,765). Of the 8670 children with a paternal history of cancer, 8162 were conceived naturally and 508 were conceived using assisted reproductive technologies (ARTs) (in vitro fertilization or intracytoplasmatic sperm injection). Of the 1,769,095 children without a paternal history of cancer, 25,926 were conceived using ARTs. Associations between paternal history of cancer and risk of adverse birth outcomes of children conceived naturally or by ARTs were investigated using log-linear binomial models, yielding risk ratios (RRs) with 95% confidence intervals (CIs). All statistical tests were two-sided. The offspring of male cancer survivors were more likely to have major congenital abnormalities than the offspring of fathers with no history of cancer (RR = 1.17, 95% CI = 1.05 to 1.31, P = .0043, 3.7% vs 3.2%). However, the mode of conception (natural conception or ARTs) did not modify the association between paternal history of cancer and risk of congenital abnormalities (natural conception, RR = 1.17, 95% CI = 1.04 to 1.31; ARTs, RR = 1.22, 95% CI = 0.80 to 1.87, P(interaction) = .84). We observed a statistically significant but modest increase in the risk of major congenital abnormalities among offspring of males with a history of cancer, independent of the mode of conception.