First trimester exposure to antithyroid drugs associated with increased risk of birth defects

Originally Published By 2 Minute Medicine®. Reused on Endocrinology Advisor with permission.
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1. First trimester exposure to anytithyroid drugs (ATDs) was associated with a greater risk of congenital malformations, especially for pregnant women who were given prescriptions for methimazole (MMI) or both MMI and propylthiouracil (PTU).

2. These results suggest that first trimester MMI use should be minimized and that the present recommendation of using PTU rather than MMI after pregnancy detection should be reevaluated.

Evidence Rating Level: 2 (Good)          

Study Rundown: Graves' disease (GD) that is insufficiently treated or not treated may give rise to serious sequelae to the fetus and mother or may cause pregnancy loss.  The ATDs PTU, MMI, and carbimazole are effective for managing GD during pregnancy.  However, these ATDs can enter the placenta and result in fetal complications, especially during the first trimester.  This nationwide Korean cohort study studied the link between maternal ATD (MMI and PTU) prescriptions and live birth congenital malformations.  Of 2 886 970 completed pregnancies associated with live births in 2 210 253 women between 2008 and 2014, researchers found that first trimester exposure to ATDs was associated with a greater risk of congenital malformations, especially for pregnant women who were given prescriptions for MMI or both MMI and PTU.  These results suggest that first trimester MMI use should be minimized and that the present recommendation of using PTU rather than MMI after pregnancy detection should be reevaluated.

A strength of the study is the use of the National Health Insurance (NHI) database, which includes the entire Korean population.  A limitation of this study is that a prescription claims databased was used to determine exposure to ATDs.

Click to read the study in Annals of Internal Medicine

Relevant Reading: Treatment of Graves' disease with antithyroid drugs in the first trimester of pregnancy and the prevalence of congenital malformation

In-Depth [retrospective cohort]: Using the Korean NHI database between 2008 and 2014, researchers evaluated a cohort of 2 886 970 completed pregnancies associated with live births in 2 210 253 women.  Of these, 12 891 (0.45%) pregnancies had first trimester ATD exposure.  Exposed infants had a 7.27% prevalence of malformations compared to 5.94% of infants whose mothers did not receive a prescription for ATDs (p < 0.001).  In comparison to pregnancies without prescriptions for ATDs, absolute increases in congenital malformations per 1000 live births for PTU alone, MMI alone, and both PTU and MMI were 8.81 cases, 17.05 cases, and 16.53 cases, respectively.  Relative increases for the risk of malformations was 31% for MMI and 16% for PTU.  The heightened risk of malformations linked to MMI exposure was also present in women who changed from MMI to PTU a few months prior to pregnancy or during the first trimester.  In addition, the authors detected a dose-response correlation between exposure to MMI and malformation risk.  A first trimester cumulative high dose of >495 mg was linked to a greater risk for malformations in comparison to a low dose of 1 to 126 mg (adjusted odds ratio: 1.87).

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