Nørgård B, Pedersen L, Jacobsen J, Rasmussen S N, Sørensen H T
Department of Clinical Epidemiology, Aarhus and Aalborg University Hospital, Aarhus, Denmark.
Aliment Pharmacol Ther. 2004 Mar 15;19(6):679-85. doi: 10.1111/j.1365-2036.2004.01889.x.
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.
To examine the risk of congenital abnormalities in children fathered by men exposed to azathioprine or mercaptopurine before conception.
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.
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).
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.
硫唑嘌呤和巯嘌呤的免疫抑制疗法常用于患有各种慢性疾病的患者。关于这些药物在受孕前父亲使用后的生殖安全性的现有数据很少且尚无定论。
研究受孕前接触硫唑嘌呤或巯嘌呤的男性所生育子女的先天性异常风险。
这是一项基于丹麦人群的队列研究，数据来自丹麦北日德兰郡的处方数据库、医疗出生登记处和医院出院登记处。纳入了54例暴露妊娠，其中父亲在受孕前开具了硫唑嘌呤或巯嘌呤的处方（1991年1月1日至2001年12月31日之间）。对照组包括57195例父亲未使用硫唑嘌呤或巯嘌呤的妊娠。
54例暴露妊娠中有4例先天性异常儿童（父亲潜在疾病：肾小球肾炎和严重皮肤病）（7.4%），而对照组中有2334例（4.1%）。接受硫唑嘌呤或巯嘌呤治疗的男性所生育子女先天性异常的校正比值比为1.8（95%置信区间，0.7 - 5.0）。
我们的数据可能表明受孕前父亲使用硫唑嘌呤或巯嘌呤与先天性异常风险增加有关。然而，需要更多数据来确定这种关联是否具有因果关系。
