What is the risk to the fetus when taking methimazole (antithyroid medication) during the first trimester of pregnancy?

From the Guidelines

Methimazole use during the first trimester of pregnancy poses a significant risk of birth defects to the fetus, specifically a condition called methimazole embryopathy, and propylthiouracil is preferred over methimazole in the first trimester due to its lower risk of teratogenicity. The risk of methimazole embryopathy includes defects such as aplasia cutis, choanal atresia, esophageal atresia, facial abnormalities, and developmental delays 1. According to the American Family Physician guidelines, propylthiouracil is recommended in the first trimester, while methimazole is preferred in the second and third trimesters due to possible teratogenicity in the first trimester with methimazole and propylthiouracil-associated hepatotoxicity in subsequent trimesters 1.

Key points to consider:

• Methimazole embryopathy is a rare but serious condition that can occur when methimazole is taken during the first trimester of pregnancy
• The risk of birth defects is highest when methimazole is taken between weeks 6-10 of pregnancy, a critical period for fetal organ development
• Propylthiouracil is generally recommended instead of methimazole in the first trimester due to its lower risk of birth defects
• After the first trimester, switching to methimazole may be considered as propylthiouracil carries a higher risk of liver damage with prolonged use 1
• Any woman of childbearing age taking methimazole should use reliable contraception or discuss medication changes with her healthcare provider before attempting pregnancy.

From the FDA Drug Label

Methimazole crosses the placental membranes and can cause fetal harm, when administered in the first trimester of pregnancy Rare instances of congenital defects, including aplasia cutis, craniofacial malformations (facial dysmorphism; choanal atresia) gastrointestinal malformations (esophageal atresia with or without tracheoesophageal fistula) omphalocele and abnormalities of the omphalomesenteric duct have occurred in infants born to mothers who received methimazole in the first trimester of pregnancy Because of the risk for congenital malformations associated with use of methimazole in the first trimester of pregnancy it may be appropriate to use other agents in pregnant women requiring treatment for hyperthyroidism If methimazole is used during the first trimester of pregnancy or if the patient becomes pregnant while taking this drug, the patient should be warned of the potential hazard to the fetus

The risk to the fetus when taking methimazole during the first trimester of pregnancy includes:

• Congenital malformations such as aplasia cutis, craniofacial malformations, gastrointestinal malformations, omphalocele, and abnormalities of the omphalomesenteric duct
• Fetal harm due to methimazole crossing the placental membranes It is recommended to use the lowest possible dose to control the maternal disease and consider alternative treatments, especially during the first trimester of pregnancy 2.

From the Research

Risk to the Fetus

The risk to the fetus when taking methimazole during the first trimester of pregnancy includes:

• Congenital malformations, such as ectodermal anomalies, choanal atresia, esophageal atresia, and omphalocele 3, 4, 5, 6
• The absolute risk of these malformations appears to be very small 3
• There is no evidence that children prenatally exposed to methimazole have an increased risk of neurodevelopmental delay 3

Comparison with Propylthiouracil

• Propylthiouracil is recommended during the first trimester of pregnancy due to the potential risks associated with methimazole 3, 5
• However, propylthiouracil has been associated with hepatotoxicity in approximately 0.1% of exposed adults 3
• Methimazole may be considered during the second and third trimesters due to the risks associated with propylthiouracil 3

Studies on Methimazole Exposure

• A case-control study found an association between prenatal exposure to maternal hyperthyroidism treated with methimazole and choanal atresia 6
• A retrospective study found no significant difference in the rates of spontaneous miscarriage and major congenital malformations between women treated with methimazole and those not treated with antithyroid drugs 7
• Another study suggested that the mother's disease might be the causal factor for choanal atresia, rather than the methimazole treatment 6