Abstract
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.
Highlights
Hyperthyroidism is a condition with increased production of thyroid hormones in the thyroid gland
Out of 1699 pregnancies, 838 (49.3%) were among women who had a first diagnosis of hyperthyroidism before pregnancy, while 861 (50.7%) pregnancies were among women with new-onset hyperthyroidism
Subanalysis adjusted for first time diagnosis of hyperthyroidism prior to pregnancy revealed the following results (Supplemental table 3): Treatment with CMZ alone during pregnancy was associated with low birth weight and preterm birth
Summary
Hyperthyroidism is a condition with increased production of thyroid hormones in the thyroid gland. Graves' disease (GD) is the most common cause of hyperthyroidism in women of reproductive age, and the main type of overt hyperthyroidism during pregnancy. Several international studies have shown an association between maternal hyperthyroidism and increased risk of preterm birth and low birth weight [6,7,8,9]. Maternal complications, such as pregnancy-induced hypertension and preeclampsia are more common in pregnancies with hyperthyroidism [8,9,10]
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