The Impact of Maternal Thyrotoxicosis and Antithyroid Drug Exposure on Fetal/Neonatal Brain Development

Abstract

Elevated maternal thyroid hormone levels during pregnancy, as well as antithyroid drugs, can influence fetal and neonatal brain development. Elevated thyroid hormone levels in pregnancy are associated with an increased risk of miscarriage, preterm delivery, intrauterine growth restriction, preeclampsia, and heart failure. Fetal exposure to excessive maternal thyroid hormone is associated with inhibition of the fetal hypothalamic–pituitary–thyroid axis, impaired maturation of pituitary thyrotrophs and thyroid gland development, and potential disruption of neurologic development. Early diagnosis and treatment of maternal hyperthyroidism during pregnancy with antithyroid drugs improves pregnancy outcomes, fetal growth, and neurologic development. The antithyroid drugs methimazole (MMI) and carbimazole (CAB), however, are associated with a rare embryopathy that may include aplasia cutis, choanal atresia, tracheoesophageal fistulas, omphalocele, omphalomesenteric duct anomalies, and facial abnormalities. Although the number of reported cases is small relative to the number of women taking MMI or CAB at the time of conception, similar congenital abnormalities have not been reported in association with exposure to the antithyroid drug propylthiouracil (PTU). Developmental delay has been described in a subset of cases of MMI/CAB-related embryopathy, potentially due to the perinatal hypoxia associated with bilateral choanal atresia. PTU has been associated with severe maternal hepatotoxicity. The current guidelines for treatment of hyperthyroidism in pregnancy reconcile the adverse profile of antithyroid drugs in pregnancy by recommending PTU in the first trimester, to minimize the risk for embryopathy, and MMI in the second and third trimesters, to minimize the risk of liver failure.