Antithyroid drugs associated with increased congenital malformation risk when taken during the first trimester of pregnancy
The risk appeared to be higher in those who received methimazole or both methimazole and propylthiouracil versus propylthiouracil alone.
Antithyroid drugs taken during the first trimester of pregnancy may be associated with an increased risk of congenital malformations, a new study has found.
Researchers in Korea performed a nationwide cohort study using a national health insurance database to determine whether maternal prescriptions for antithyroid drugs were associated with congenital malformations in live births. Completed pregnancies were linked with live-born infants between 2008 and 2014. Risks for overall and organ-specific congenital malformations in offspring were examined, controlling for potential confounders. The results were published online Jan. 22 by Annals of Internal Medicine.
The cohort included 2,886,970 completed pregnancies in 2,210,253 women. A total of 12,891 pregnancies (0.45%) were exposed to antithyroid drugs during the first trimester. Of these, 77.0% received propylthiouracil only, 8.7% received methimazole only, and 14.3% received both drugs. Exposed offspring had a malformation prevalence of 7.27% versus 5.94% in offspring of women who did not have a prescription for antithyroid drugs during pregnancy (P<0.001; adjusted odds ratio, 1.19; 95% CI, 1.12 to 1.28). When specific drugs were considered, absolute increases in prevalence of congenital malformations per 1,000 live births were 8.81 cases for propylthiouracil only, 17.05 cases for methimazole only, and 16.53 cases for both drugs versus pregnancies without antithyroid drug prescriptions. Among patients prescribed methimazole during the first trimester, a high cumulative dose, defined as greater than 495 mg, was associated with increased malformation risk versus a low cumulative dose, defined as 1 to 126 mg (adjusted odds ratio, 1.87; 95% CI, 1.06 to 3.30).
The authors noted that their study was based on a prescription claims database and that some women who were prescribed antithyroid drugs may not have taken them, among other limitations. However, they concluded that exposure to antithyroid drugs during the first trimester of pregnancy was associated with a significant increased risk for congenital malformations and that this risk appeared to be higher in those who received methimazole or both methimazole and propylthiouracil versus propylthiouracil alone.