High-dose methotrexate during pregnancy: risk of malformations

Methotrexate is a cytotoxic and immunosuppressant drug mainly used in oncology and rheumatology. It is sometimes used at high doses to treat unruptured ectopic pregnancy. Methotrexate is teratogenic. Malformations reported after exposure in utero include: abnormalities of the skull and face, limb defects, failure of ossification, and congenital cardiopathy.The risk of malformations is probably dose-dependent and seems to be relatively low at the low weekly doses used in rheumatology. Three cases of malformations have been reported after failure of high-dose methotrexate in pregnancies that were misdiagnosed as ectopic. Two newborns had scoliosis, facial dysmorphism, limb malformations, or cardiopathy.The third newborn had minor malformations. In practice, high-dose methotrexate must only be used to treat ectopic pregnancy if the diagnosis has been confirmed. The woman should be informed of the risks to her unborn child in case of diagnostic error or treatment failure.