Bawle E V, Conard J V, Weiss L
Children's Hospital of Michigan, Wayne State University, Detroit 48201, USA.
Teratology. 1998 Feb;57(2):51-5. doi: 10.1002/(SICI)1096-9926(199802)57:2<51::AID-TERA2>3.0.CO;2-9.
The folic acid antagonists, methotrexate and aminopterin, are known to be teratogenic in humans. The critical period for their teratogenecity is suspected to be between 6 to 8 weeks post-conception. Fetal exposure from 10 to 32 weeks weeks post-conception to methotrexate alone or in combination with other anti-cancer drugs has not resulted in obvious teratogenic effects. Methotrexate is often used to treat cancers but is occasionally used as an abortifacient. The long-term outcome of the fetal aminopterin syndrome has been published in only four adults. We report on a 28-year-old man with fetal methotrexate syndrome and two children with mild manifestations of the syndrome. One child was inadvertently exposed to methotrexate from 7 1/2 through 30 weeks post-conception because his mother was receiving it for treatment of breast cancer. The other was exposed from 11 weeks and 5 days through 25 weeks in an attempt to induce abortion. The 28-year-old man has craniofacial and digital anomalies, growth retardation but normal intelligence as noted in the previously reported cases. These cases remind us of the teratogenicity of methotrexate and should serve as a warning that if methotrexate is used as an abortifaciant and an abortion does not ensue, there is a teratogenic risk.
已知叶酸拮抗剂甲氨蝶呤和氨蝶呤对人类具有致畸性。怀疑其致畸的关键时期是在受孕后6至8周之间。受孕后10至32周胎儿单独暴露于甲氨蝶呤或与其他抗癌药物联合使用，尚未产生明显的致畸作用。甲氨蝶呤常用于治疗癌症，但偶尔也用作堕胎药。胎儿氨蝶呤综合征的长期结果仅在4名成年人中发表过。我们报告了一名患有胎儿甲氨蝶呤综合征的28岁男性以及两名有该综合征轻度表现的儿童。一名儿童在受孕后7.5周至30周期间意外接触了甲氨蝶呤，因为他的母亲正在接受该药治疗乳腺癌。另一名儿童在11周零5天至25周期间接触甲氨蝶呤，目的是引产。这名28岁男性有颅面和手指异常、生长发育迟缓，但智力正常，这与之前报道的病例情况一致。这些病例提醒我们甲氨蝶呤的致畸性，并且应作为一个警示：如果将甲氨蝶呤用作堕胎药但未导致流产，存在致畸风险。
