Fetal Risk Assessment of an Unintended Pregnancy Exposed to Methotrexate and Leflunomide in a Patient with Rheumatoid Arthritis

OBJECTIVE To provide reference for the risk assessment and consultation of medication use during pregnancy by sharing practice of fetal risk assessment of a patient with rheumatoid arthritis who was exposed to leflunomide and methotrexate within 16 weeks of unintended pregnancy. METHODS Pharmacists fully reviewed the relevant literatures at home and abroad, and analyzed the possible impacts of methotrexate and leflunomide on fetus from the aspects of drug metabolism characteristics, animal reproductive toxicity and human pregnancy evidence with the aid of pregnancy drug risk assessment tools. The patient was fully informed, then pregancy registry and follow-up were performed. RESULTS Information about drug-induced fetal malformation and developmental abnormalities mostly came from animal studies and case reports, but some large cohort studies had optimistic data. On the evidence so far, no conclusion could be drawn on the risk of leflunomide and methotrexate use during pregnancy. The risk of drug exposure couldn't be excluded, but the dose taken by the patient was lower than the teratogenic dose reported in the literature, which need to be taken into consideration and the risks and benefits should be weighed carefully. The patient continued pregnancy, and successfully gave birth to a small-for- gestational-age baby at term without obvious deformities in appearance, skeleton, and internal organs. CONCLUSION The low-dose leflunomide and methotrexate exposure did not increase the risk of birth defects in this case. The fetal growth restriction may be related to both maternal conditions and medication exposure, and further follow-up for long-term outcome of the baby is required.