Randomised controlled trials (RCTs), cohort studies, longitudinal observational studies and surveys that evaluated the effects of methotrexate at doses used in rheumatology (7.5 to 25mg per week), in adults (aged over 18 years) with rheumatoid arthritis, were eligible for inclusion. Studies had to evaluate the following: male or female fertility; pregnancy complications, malformations, miscarriages, induced abortions and still births; breast feeding complications, infections, immunosuppression; or dose of methotrexate in human milk.
In the included studies of methotrexate and pregnancy, the mean methotrexate dose ranged from 5 to 25mg per week, women were exposed to methotrexate from conception to the first trimester of pregnancy, and their mean age ranged from 28 to 35 years (where reported).
Two reviewers independently selected studies and resolved disagreements by consensus.