Is methotrexate (MTX) safe for pregnant women with rheumatoid arthritis (RA)?

Updated: May 11, 2018
  • Author: Katherine K Temprano, MD; Chief Editor: Christine Isaacs, MD  more...
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Methotrexate (MTX), a folic acid antagonist, is contraindicated in pregnancy (category X), because it is an abortifacient and has teratogenic effects, such as causing the development of craniofacial abnormalities, limb defects, and such CNS defects as anencephaly, hydrocephaly, and meningomyelopathy, especially with first-trimester exposure. [20] Because its active metabolites have a long half-life, methotrexate must be discontinued at least 3 months before conception; compensatory treatment with folic acid should be continued during that period and throughout pregnancy. Male partners should also discontinue methotrexate at least 3 months prior to attempting to conceive.

Pregnancy outcomes in women taking MTX (≤30 mg/week) either after conception or within 12 weeks before conception were evaluated in a prospective observational multicenter cohort study and compared with disease-matched women and women without autoimmune diseases. Major birth defects were more common in women with MTX exposure postconception than in the nondiseased comparison group (odds ratio [OR] 3.1, 1.03–9.5). However, there was no significant increase when compared with disease-matched controls. There was no difference in birth defects among women with exposure only in preconception and the two comparison groups. No birth defects in either exposure group were consistent with MTX embryopathy. [25]  While this information is helpful in risk managmenet counseling if an unplanned pregnancy occurs, MTX should always be discontinued prior to conception when pregnancy is being planned (category X). If a woman is receiving MTX, she should be using concomitant contraception.

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