Methimazole is contraindicated in the first trimester of pregnancy because it is associated with which rare congenital syndrome?

Explanation

## Methimazole Teratogenicity **Key Point:** Methimazole crosses the placenta and is associated with a rare but distinctive pattern of congenital anomalies termed **methimazole embryopathy**, characterized by aplasia cutis (scalp defects), choanal atresia, and esophageal atresia. This risk is highest in the first trimester. ## Antithyroid Drugs in Pregnancy | Trimester | Drug of Choice | Rationale | | --- | --- | --- | | First trimester | PTU | Methimazole carries teratogenic risk (embryopathy); PTU has lower placental transfer | | Second & third trimester | Methimazole preferred | Lower hepatotoxicity risk; PTU black box warning for liver failure | | Postpartum | Either (based on clinical need) | Risk–benefit reassessed | **High-Yield:** PTU is the preferred antithyroid drug in the first trimester despite its hepatotoxicity risk because the teratogenic risk of methimazole outweighs the hepatic risk in this critical window. Many guidelines recommend switching to methimazole after the first trimester to reduce PTU-related liver toxicity. **Mnemonic: METH = Methimazole Embryopathy — Thyroid (defects), Hematologic (anemias), Esophageal/choanal atresia** **Clinical Pearl:** The incidence of methimazole embryopathy is approximately 1–2% of exposed pregnancies. Neonatal hypothyroidism (from transplacental passage of the drug) is transient and resolves as the drug is cleared; permanent fetal hypothyroidism is not a direct teratogenic effect but rather a pharmacological consequence.