Congenital malformations in Grave’s disease

Traditional approach is to use propylthiouracil (PTU) for Grave’s disease during the first trimester. This article points otherwise, that both methimazole and PTU can increase the risk of congenital malformations when used in the first three months of pregnancy. I suspect more research would be needed before changing guidelines or standard of care.


Also see:

Other related thyroid-pregnancy articles


Annals of Internal Medicine


January 2018


Untreated or insufficiently treated Graves disease in pregnancy may pose risks to both mother and fetus. Antithyroid drugs (ATDs) are the treatment mainstay, but the potential teratogenic effect of these drugs has prompted clinicians to question the safe management of this vulnerable population.


To examine the association between maternal prescriptions for ATDs and congenital malformations in live births. Nationwide cohort study. Korean National Health Insurance database. A cohort of 2,886,970 completed pregnancies linked to live-born infants in 2,210,253 women between 2008 – 2014.


Maternal prescriptions for ATDs in the first trimester. The risk for overall and organ-specific congenital malformations in offspring, with logistic regression models used to control for potential confounders.


12,891 pregnancies (0.45%) were exposed to ATDs during the first trimester. The prevalence of malformations in exposed offspring was 7.27%, compared with 5.94% in offspring of women who were not prescribed ATDs during pregnancy (adj OR 1.19, p< 0.001).

Absolute increases in the prevalence of congenital malformations per 1000 live births were 8.81 cases for propylthiouracil alone, 17.05 cases for methimazole (MMI) alone, and 16.53 cases for propylthiouracil and MMI, compared with pregnancies without ATD prescriptions (all p<0.05).

In the MMI group, a high cumulative dose (>495 mg) during the first trimester was associated with an increased risk for malformations compared with a low dose (<126 mg) – adj OR 1.87, p<0.05.

Limitation: the study used a prescription claims database to assess ATD exposure.


Exposure to ATDs during the first trimester was associated with increased risk for congenital malformations, particularly for pregnancies in which women received prescriptions for MMI or both ATDs.