Use of Methotrexate in Girls and Women of Childbearing Age, Occurrence of Methotrexate-Exposed Pregnancies and Their Outcomes in Germany: A Claims Data Analysis.

Background And Objective: Methotrexate should be withdrawn before pregnancy because of its teratogenic potential. We aimed to describe the use of methotrexate in women of childbearing age in Germany and the occurrence and outcomes of pregnancies exposed to methotrexate.

Methods: Using the German Pharmacoepidemiological Research Database (GePaRD, covering ~ 20% of the German population), we determined the age-specific and age-standardized prevalence of methotrexate use for each year between 2004 and 2019 among women aged 13-49 years (cross-sectional analyses). In a cohort analysis, we assessed the number and outcomes of pregnancies exposed to methotrexate in the critical time window. Exposure was defined as a dispensation overlapping with the onset of pregnancy or a dispensation in the first 8 weeks of pregnancy. For children born from exposed pregnancies, the mother's and children's data were linked and the occurrence of malformations was assessed by reviewing all available data of these children.

Results: The age-standardized prevalence of methotrexate use per 1000 females increased from 1.5 in 2004 to 2.3 in 2019, i.e., by 52%. Overall, we identified 184 pregnancies exposed to methotrexate. Of these, 53% ended in a live birth (21% preterm) and 11% in an induced abortion. Among 81 live-born children linked to their mothers, five children (6%) had relevant malformations including congenital heart defects and musculoskeletal malformations.

Conclusions: In Germany, the use of methotrexate in women of childbearing age has substantially increased since 2004. Despite the known teratogenic effect, there was a considerable number of exposed pregnancies.  Also, malformations likely associated with methotrexate and thus avoidable were observed.