Teratogen update: Antithyroid drugs - Methimazole, carbimazole, and propylthiouracil

Antithyroid drugs are the treatment of choice for thyrotoxicosis in pregnancy. They do not represent major human teratogens. Data is insufficient to draw a definitive conclusion as to the teratogenic potential of MMI and CMZ. There are no prospective controlled studies supporting the teratogenicity of MMI. A cluster of case reports of ACC in association with prenatal MMI exposure suggests a probable weak association. They may be a result of a reporting bias. Controlled cohort studies will probably not give an answer because, for rare anomalies, their sample size may be inadequate. A case-control study comparing the incidence of ACC among offspring of women treated with MMI in pregnancy compared to another rare anomaly may provide an answer. A comparative study of the incidence of ACC among infants of women treated in pregnancy with MMI vs. PTU may further help. A rare MMI embryopathy has been suggested in the literature. The evidence is yet insufficient to substantiate a causal relationship. PTU has not been implicated in increasing the rate of major malformations in most studies. It may be advantageous over MMI or CMZ in pregnancy due to the lack of an association between PTU and ACC or an embryopathy, even if placental transfer of both drugs is similar. With all antithyroid drugs, if used after the 10th gestational week, fetal toxicity should be looked for. Congenital goiter, thyroid dysfunction, or both occasionally occur. The risk is probably minimal after maternal treatment with MMI or CMZ and small after PTU, but prospective studies are still needed for a true risk estimate. In most cases, the effect is transient, and resolves spontaneously. Infants are at increased risk for hyperthyroidism due to placental transfer of thyroid stimulating immunoglobulins, as well as for hypothyroidism and goiter due to a direct drug effect. Prenatal ultrasonographic assessment of fetal thyroid gland is advised in women who are treated with antithyroid drugs during pregnancy. Invasive procedures should be considered in cases of significant enlargement of the thyroid gland or hydrops fetalis. Post natal assessment of neonatal thyroid fimction should be performed.