Background : Immunosuppressive therapy with azathioprine and mercaptopurine is commonly used in patients with various chronic diseases. The few existing data on the reproductive safety of these drugs after paternal use before conception are inconclusive.

Aim : To examine the risk of congenital abnormalities in children fathered by men exposed to azathioprine or mercaptopurine before conception.

Methods : This was a Danish population-based cohort study, based on data from the Prescription Database, the Medical Birth Registry and the Hospital Discharge Registry of North Jutland County, Denmark. Fifty-four exposed pregnancies, in which the father filed a prescription for azathioprine or mercaptopurine (between 1 January 1991 and 31 December 2001) before conception, were included. The controls comprised 57 195 pregnancies with no paternal azathioprine or mercaptopurine use.

Results : Four children with congenital abnormalities (underlying paternal diseases: glomerulonephritis and severe skin disease) were found in 54 exposed pregnancies (7.4%), compared with 2334 (4.1%) in controls. The adjusted odds ratio for congenital abnormalities in children fathered by men treated with azathioprine or mercaptopurine was 1.8 (95% confidence interval, 0.7–5.0).

Conclusions : Our data may indicate that paternal use of azathioprine or mercaptopurine before conception is associated with an increased risk of congenital abnormalities. However, more data are needed to determine whether the association is causal.