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Prenatal antithyroid drug exposure increases risk for birth defects

Maternal use of antithyroid drugs, such as methimazole and propylthiouracil, during the first trimester of pregnancy was linked to a higher risk for congenital malformations, according to findings published in Annals of Internal Medicine.

“Untreated or insufficiently treated Graves disease in pregnancy may pose risks to both mother and fetus,” Gi Hyeon Seo, MD, from the Health Insurance Review and Assessment Service, Wonju-si, Gwangwon-do, Korea, and colleagues wrote. “Antithyroid drugs are the treatment mainstay, but the potential teratogenic effect of these drugs has prompted clinicians to question the safe management of this vulnerable population.”

Seo and colleagues performed a nationwide cohort study in Korea to investigate if antithyroid drug use during the first trimester of pregnancy increases the risk for congenital malformations in live births. The researchers used the Korean National Health Insurance database to identify 2,886,970 completed pregnancies with live-born infants between 2008 to 2014 in 2,210,253 women. Of these pregnancies, 12,891 were exposed to antithyroid drugs during the first trimester.

Malformations were observed in 7.27% of the exposed offspring, compared with 5.94% of those not exposed to antithyroid drugs (adjusted OR = 1.19; 95% CI, 1.12-1.28). Compared with pregnancies with no exposure to antithyroid drugs, prenatal exposure to methimazole during the first trimester increased the risk for congenital malformations by 31% and exposure to propylthiouracil increased the risk by 16. This translated to 17.05 additional cases per 1,000 live births for methimazole and 8.81 additional cases per 1,000 live births for propylthiouracil.

During the first trimester, a high cumulative dose of methimazole of more than 495 mg increased risk for malformations compared with a low dose of 1 mg to 126 mg (aOR = 1.87; 95% CI, 1.06-3.3).

“[Antithyroid drug] exposure during the first trimester was associated with significantly increased risk for congenital malformations, particularly for pregnancies in which women received prescriptions for [methimazole] or both [antithyroid drugs]. These findings confirm the importance of minimizing [methimazole] use in the first trimester and suggest that the current recommendation of switching from [methimazole] to [propylthiouracil] after pregnancy detection be reconsidered.” – by Alaina Tedesco

Disclosure: The authors report no relevant financial disclosures.