Methotrexate embryopathy after exposure to low weekly doses in early pregnancy

Reprod Toxicol. 2014 Jan:43:26-9. doi: 10.1016/j.reprotox.2013.10.005.


Objective: Methotrexate (MTX) is a potent teratogen when used in high doses for cancer or termination of tubal pregnancy. In contrast, it has been perceived as safe when used once weekly at low dose for rheumatological conditions.

Methods: A prospective observational controlled study of women exposed to low dose MTX. The control group were women exposed to MTX only before conception.

Results: Among the 8 MTX-exposed pregnancies, there was a case of typical MTX embryopathy, the first to be described to date at this lower once weekly dose Schedule.

Conclusions: This case has important implications for rheumatologists treating women of reproductive age, as the assumption of fetal safety of MTX, implied from small cohorts, is premature.

Publication types

  • Case Reports

MeSH terms

  • Abnormalities, Multiple / chemically induced*
  • Adolescent
  • Adult
  • Antirheumatic Agents / adverse effects*
  • Antirheumatic Agents / therapeutic use
  • Craniofacial Abnormalities / chemically induced*
  • Female
  • Fetal Diseases / chemically induced*
  • Humans
  • Maternal-Fetal Exchange
  • Methotrexate / adverse effects*
  • Methotrexate / therapeutic use
  • Pregnancy
  • Rheumatic Diseases / drug therapy
  • Young Adult


  • Antirheumatic Agents
  • Methotrexate