Cassina M, Johnson D L, Robinson L K, Braddock S R, Xu R, Jimenez J L, Mirrasoul N, Salas E, Luo Y J, Jones K L, Chambers C D
University of Padua, Padua, Italy.
Arthritis Rheum. 2012 Jul;64(7):2085-94. doi: 10.1002/art.34419.
Findings from animal studies have suggested that leflunomide may be a human teratogen. In the only human cohort study published to date, an increase in adverse outcomes in pregnancies after exposure to leflunomide was not detected. The aim of the present analysis was to expand on the previously published data with a description of birth outcomes among women who did not meet the previous cohort study criteria but who were exposed to leflunomide either during pregnancy or prior to conception.
Data on pregnancy exposures and outcomes were collected from 45 pregnant women who had contacted counseling services of the Organization of Teratology Information Specialists in the US or Canada between 1999 and 2009. Sixteen women were exposed to leflunomide during the first trimester of pregnancy and 29 women were exposed preconception.
All 16 of the pregnancies with leflunomide exposure during pregnancy and 27 (93%) of the pregnancies with exposure prior to conception resulted in liveborn infants. There were 2 infants with major malformations from mothers who were exposed during pregnancy, and no malformations reported in the preconception group. There was a potential known alternative etiology for at least some of the defects observed.
These data provide additional reassurance to women who inadvertently become pregnant while taking leflunomide and who undergo the washout procedure, as well as women who discontinue the medication prior to conception but have no prepregnancy documentation of drug clearance. However, until more conclusive data become available, women receiving leflunomide should be advised to use contraceptive methods and avoid pregnancy.
动物研究结果表明来氟米特可能是一种人类致畸剂。在迄今为止发表的唯一一项人类队列研究中，未检测到来氟米特暴露后妊娠不良结局增加。本分析的目的是扩展先前发表的数据，描述未符合先前队列研究标准但在孕期或受孕前暴露于来氟米特的女性的出生结局。
收集了1999年至2009年间联系美国或加拿大致畸信息专家组织咨询服务的45名孕妇的妊娠暴露和结局数据。16名女性在妊娠早期暴露于来氟米特，29名女性在受孕前暴露。
孕期暴露于来氟米特的所有16例妊娠以及受孕前暴露的27例（93%）妊娠均产下活婴。孕期暴露的母亲中有2例婴儿患有严重畸形，受孕前暴露组未报告畸形。至少部分观察到的缺陷存在已知的潜在替代病因。
这些数据为在服用来氟米特时意外怀孕并接受洗脱程序的女性，以及在受孕前停药但无孕前药物清除记录的女性提供了更多安心。然而，在获得更确凿的数据之前，应建议接受来氟米特治疗的女性采用避孕方法并避免怀孕。
