Methotrexate is a proven teratogen and its use periconceptually is strongly advised against. Concerns about possible chromosomal effects in the offspring of women treated with this agent have been raised, but they have not been reported. In vivo and in vitro studies have supported this possibility, however.
A 32-year-old primigravida was treated with low-dose methotrexate for rheumatoid arthritis from prior to conception until six weeks postconception. Her child was born without congenital malformations but subsequently developed seizures and was diagnosed with developmental delay. He was found to have a de novo, apparently balanced, reciprocal translocation between chromosomes 5 and 20 (46,XY,t(5:20)(q15;p12)). Other investigations failed to reveal another cause for his developmental delay.
The possible association between maternal methotrexate exposure and a de novo chromosomal anomaly in an offspring supports the recommendation that women should be advised to cease taking this drug for at least six months prior to conception.