Midtvedt Karsten, Bergan Stein, Reisæter Anna Varberg, Vikse Bjørn Egil, Åsberg Anders
1 Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway. 2 Department of Pharmacology, Oslo University Hospital, Oslo, Norway. 3 Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway. 4 Norwegian Renal Registry, Oslo University Hospital, Rikshospitalet, Oslo, Norway. 5 Department of Clinical Medicine, University of Bergen, Bergen, Norway. 6 Department of Medicine, Haugesund Hospital, Haugesund, Norway.
Transplantation. 2017 Jul;101(7):e214-e217. doi: 10.1097/TP.0000000000001747.
Mycophenolic acid (MPA) is the active immunosuppressive substance in both mycophenolate mofetil and mycophenolate sodium, and it is widely used after organ transplantation. In women, taking MPA is teratogenic and may also influence spermatogenesis. There is a lack of knowledge regarding outcome of pregnancies fathered by men exposed to MPA.
We compared outcomes in pregnancies fathered by renal transplant men per whether they had been exposed to MPA or not at time of conception. A nationwide population-based retrospective cohort study was performed. Data from the Norwegian Renal Registry with all renal transplanted men alive between January 1, 1995 and December 31, 2015 were included, and relevant outcome data were extracted from the Medical Birth Registry of Norway.
During the given time, 230 immunosuppressed renal transplanted men fathered 350 children (155 on MPA/195 not on MPA). There were no significant increased risks of malformation (3.9% vs. 2.6%, P = 0.49) in MPA exposed versus unexposed cohorts of children. The average dose (±SD) of mycophenolate was 1.42 ± 0.3 g/day and the individual median MPA trough concentration in the time period of anticipated conception and pregnancy was 2.8 ± 1.6 mg/L. Birth weight was similar in exposed and unexposed cohorts of children; 3381 ± 681 g vs. 3429 ± 714 g (P = 0.53).
Paternal exposure to MPA did not increase the risk of adverse birth outcomes in children fathered by male kidney transplanted patients. These results are reassuring and support the continuation of paternal MPA treatment before, during, and after conception.
霉酚酸（MPA）是霉酚酸酯和霉酚酸钠中的活性免疫抑制物质，在器官移植后广泛应用。对于女性而言，服用MPA具有致畸性，并且可能影响精子生成。关于接触MPA的男性所育子女的妊娠结局，目前了解不足。
我们比较了肾移植男性在受孕时是否接触MPA所育子女的妊娠结局。开展了一项基于全国人群的回顾性队列研究。纳入了挪威肾脏登记处1995年1月1日至2015年12月31日期间所有存活的肾移植男性的数据，并从挪威医学出生登记处提取了相关结局数据。
在给定时间内，230名接受免疫抑制治疗的肾移植男性育有350名子女（155名子女的父亲服用MPA，195名子女的父亲未服用MPA）。接触MPA与未接触MPA的子女队列中，畸形风险没有显著增加（3.9%对2.6%，P = 0.49）。霉酚酸的平均剂量（±标准差）为1.42±0.3克/天，在预期受孕和妊娠期间个体霉酚酸谷浓度中位数为2.8±1.6毫克/升。接触MPA与未接触MPA的子女队列中出生体重相似；分别为3381±68克与3429±714克（P = 0.53）。
男性肾移植患者父亲接触MPA不会增加其所育子女不良出生结局的风险。这些结果令人安心，并支持在受孕前、受孕期间和受孕后继续对父亲进行MPA治疗。
