Background: Hyperthyroidism is associated with maternal, obstetrical and fetal complications during pregnancy. Antithyroid drugs (ATD) are the main therapy for hyperthyroidism. Observational studies, however, show an increased risk of birth defects for carbimazole and methimazole (CMZ/MMI). Propylthiouracil (PTU) is assumed to be the safer alternative for the unborn child, even though it can induce liver injury in the mother. A “Dear Doctor letter” issued in 2019 recommended that i) women planning a pregnancy and treated with TMZ/MMI should be switched to PTU before conception and ii) the use of TMZ/MMI in the 1st trimester should be limited to intolerance to PTU.
Objectives: To assess the occurrence of pregnancies under ATD and examine switching patterns and their changes over time.
Methods: In a cohort of 57,516 female ATD users aged 13-49 years in the German Pharmacoepidemiological Research Database (GePaRD), we identified all pregnancies exposed to ATD between 2005 and 2020. Exposure was defined as an ATD dispensing during pregnancy or an ATD supply overlapping the pregnancy beginning (supply estimated based on the number of dispensed defined daily doses). We described the type of ATD used before and during pregnancy. The study was financed by the German Federal Institute for Drugs and Medical Devices (BfArM).
Results: Overall, we identified 4,446 exposed pregnancies, of which 81.9% ended in a live birth, 0.4% in a stillbirth, 3.4% in an induced abortion, 1.4% in a spontaneous abortion, 1.5% were ectopic pregnancies and 11.4% of pregnancies did not have a recorded outcome (assumed to be spontaneous abortions not requiring medical treatment or induced abortions without medical indication). In 2,203 pregnancies (49.6%), the woman was already on ATD treatment at pregnancy onset, thereof 82.8% used CMZ/MMI (no clear changes over time). In 30.2% of these pregnancies, CMZ/MMI was also dispensed during the 1st trimester. The percentage switching to PTU increased from 43.5% in 2005-2008 to 59.5% in 2017-2020. Of those using PTU at pregnancy onset, 54.9% had used CMZ/MMI before pregnancy, i.e. they had switched to PTU. The switch occurred in median 5 (25%-75%: 2-13) months before pregnancy. The percentage switching to PTU before onset of pregnancy increased from 43.5% in 2005-2008 to 56.5% in 2017-2018 and was 75% in 2020. Of the 2,243 pregnancies starting ATD treatment during pregnancy, 1,114 (49.7%) started with CMZ/MMI thereof 67.1% during the 1st trimester. This percentage decreased from 70.3% in 2005 to 30.8% in 2020.
Conclusions: Our study showed that exposure to CMZ/MMI during the first trimester decreased, but there is still a considerable number of pregnancies exposed to these drugs.