Impact of rheumatoid arthritis and methotrexate on pregnancy outcomes: retrospective cohort study of the Italian Society for Rheumatology

OBJECTIVE: To evaluate the impact of rheumatoid arthritis (RA) and methotrexate (MTX) on the probability of becoming pregnant, pregnancy losses, elective termination of pregnancy (TOP) and congenital malformations. METHODS: A retrospective cohort study on administrative healthcare databases was conducted. Three patients’ cohorts were enrolled among childbearing-age women. The first cohort included patients with RA starting MTX between July 2004 and December 2011. The second cohort included patients with RA without MTX treatment randomly selected from the same population (ratio 1:1). Finally, a cohort of subjects without RA was identified (ratio 1:4). Multivariate logistic regression models were implemented, ORs and 95% CI were reported. RESULTS: The two matched RA cohorts included 3564 patients with MTX and without MTX. The cohort without RA included 14 256 subjects. In the three cohorts, the proportion of women achieving pregnancy during follow-up was 6.3%, 9.1% and 11.9%, respectively. Congenital malformations were very rare in all cohorts. RA women treated with MTX at any time before conception showed significantly higher risks of pregnancy losses than non-RA women (OR (95% CI) 2.22 (1.40 to 3.45)). We observed a significant positive relationship between the exposure to MTX in the 3 months window before conception and increased risk of elective TOP (OR (95% CI) 4.77 (1.08 to 19.40)). CONCLUSION: MTX-treated patients appeared to be the cohort with the highest risk of pregnancy losses. The positive association with elective TOP and exposure to MTX in the three months window before conception in patients with RA reinforces the need for adequate preconception counselling to avoid unplanned pregnancies.