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

Aims: The aim of this study was two-fold: i) to describe factors associated with antithyroid drug (ATD) treatmentduring gestation among women with hyperthyroidism in pregnancy, ii) to investigate the impact of ATDtreatment during gestation on pregnancy outcomes.Methods: Women with hyperthyroidism in pregnancy and ATD treatments were identified through linkage ofthree national registries (2008-2018): The Medical Birth Registry of Norway, the Norwegian PrescriptionRegistry and the Norwegian Patient Registry. Pregnancies were categorized as ATD treated or untreated basedon 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. Generalizedestimating 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 treatedwith ATD in 44.4% of the pregnancies, while 55.6% were untreated. Pregnant women treated with ATD hadmore often asthma compared to untreated women. Prenatal exposure to CMZ was associated with increased riskof preterm birth (aOR 1.8, 95% CI 1.1-2.8) whereas PTU exposure in the first trimester was associated with anincreased risk of cardiac malformations (aOR 9.0, 95% CI 1.8-44.7). There was no association between ATDtreatment in pregnancy and maternal preeclampsia (aOR 0.8, 95% CI 0.4-1.3) and gestational hypertension (aOR0.9, 95% CI 0.5-1.8).Conclusion: This nationwide registry study found an association between treatment with carbimazole and increasedrisk of preterm birth. Exposure to propylthiouracil in the first trimester was associated with an increasedrisk of cardiac malformations. These findings should be interpreted in light of international findings on the riskof untreated hyperthyroidism and the potential risk of ATD treatment for the mother and child.