Carbimazole, methimazole and propylthiouracil: Use in women of childbearing age and exposed pregnancies in Germany

BackgroundHyperthyroidism during pregnancy is associated with maternal, obstetrical and fetal complications. Antithyroid drugs (ATD) including carbimazole (CMZ), methimazole (MMI) and propylthiouracil (PTU) are the main pharmacotherapy for hyperthyroidism. Exposure to CMZ and MMI during the first trimester was associated with birth defects, while PTU is assumed to be the safer alternative. ObjectiveTo calculate the prescription prevalences of ATD in women of childbearing age over time and to describe pregnancies occurring after or during ATD use. MethodsUsing the GePaRD database (claims data; 20% of the German population), we conducted year-wise cross-sectional studies for the period 2004-2020 to calculate prescription prevalences of CMZ, MMI and PTU in females aged 13-49 years. In longitudinal analyses, we included all women with any ATD dispensing between 2005 and 2020 aged 13- 49 years at the first dispensing. We identified pregnancies occurring in this cohort and described ATD use before and during pregnancy. ResultsThe age-standardized prescription prevalence of ATDs decreased by 32.1% between 2004 (2.71 per 1,000) and 2020 (1.84 per 1,000). This decrease was attributable to CMZ (2004: 1.40 per 1,000; 2020: 0.76 per 1,000; relative decrease: 45.7%) and MMI (2004: 1.25 per 1,000; 2020: 0.99 per 1,000; relative decrease: 20.8%). In the cohort including 9,723 women, 13,586 pregnancies were observed, of which 67% (n=9,140) occurred after ATD use. In 16.2% of the pregnancies (n=2,203), ATD use overlapped with pregnancy onset. The proportion exposed to CMZ/MMI at pregnancy onset decreased from 30.7% in 2005 to 10.9% in 2020. In 16.5% of pregnancies (n=2,243), ATD use was started during pregnancy. ConclusionThe prescription prevalence of ATD overall and specifically of CMZ/MMI in girls and women of childbearing age decreased between 2005 and 2020 in Germany. The decrease in exposure to CMZ/MMI at pregnancy onset indicate that physicians became increasingly aware of the potential risks of CMZ/MMI to the unborn child.