*8.4.3 Methotrexate*

Methotrexate (MTX) is a folate antagonist – it inhibits the enzyme dihydrofolate reductase which impairs purine and pyrimidine synthesis. It is contraindicated during pregnancy, due to its teratogenic effects. MTX exposure *in utero* can induce multiple congenital abnormalities, such as cleft palate, hydrocephalus, anencephaly and meningoencephalocele, delayed ossification and multiple facial deformities. It is strongly advised contraceptive use in patients taking MTX. This medication should be discontinued 3 months before attempting to conceive. If a woman is being treated with a low dose of MTX within 3 months prior to conception, or an accidental pregnancy occurs, the drug should be stopped immediately and the mother should continue to take folate supplementation (5 mg daily) throughout pregnancy. In the last case, a careful evaluation of fetal risk at an experienced center must take place [67].
