Antithyroid drug treatment and pregnancy outcomes among women with hyperthyroidism in pregnancy: A Norwegian population-based registry-linkage study

Abstract

Aims: The aim of this study was two-fold: i) to describe factors associated with antithyroid drug (ATD) treatment during gestation among women with hyperthyroidism in pregnancy, ii) to investigate the impact of ATD treatment during gestation on pregnancy outcomes. Methods: Women with hyperthyroidism in pregnancy and ATD treatments were identified through linkage of three national registries (2008-2018): The Medical Birth Registry of Norway, the Norwegian Prescription Registry and the Norwegian Patient Registry. Pregnancies were categorized as ATD treated or untreated based on filled prescriptions indicating ATD exposure during pregnancy. ATD treatment was examined by trimester (T1, T2/T3) and by substance carbimazole (CMZ), propylthiouracil (PTU) and by both CMZ/PTU. Generalized estimating equations analysis with a robust variance estimator was used to estimate adjusted odds ratio (aOR) and adjusted standardized mean difference (aSMD) with 95% confidence interval (CI). Results: We identified 1699 pregnancies with hyperthyroidism during gestation. Hyperthyroidism was treated with ATD in 44.4% of the pregnancies, while 55.6% were untreated. Pregnant women treated with ATD had more often asthma compared to untreated women. Prenatal exposure to CMZ was associated with increased risk of preterm birth (aOR 1.8, 95% CI 1.1-2.8) whereas PTU exposure in the first trimester was associated with an increased risk of cardiac malformations (aOR 9.0, 95% CI 1.8-44.7). There was no association between ATD treatment in pregnancy and maternal preeclampsia (aOR 0.8, 95% CI 0.4-1.3) and gestational hypertension (aOR 0.9, 95% CI 0.5-1.8). Conclusion: This nationwide registry study found an association between treatment with carbimazole and increased risk of preterm birth. Exposure to propylthiouracil in the first trimester was associated with an increased risk of cardiac malformations. These findings should be interpreted in light of international findings on the risk of untreated hyperthyroidism and the potential risk of ATD treatment for the mother and child.