妊娠期和哺乳期妇女抗甲状腺药物的安全性评价

Evaluation the Safety of Methimazole and Propylthiouracil in Pregnancy and Lactation

目的考察抗甲状腺药物甲巯咪唑(methimazole,MMI)和丙硫氧嘧啶(propylthiouracil,PTU)在妊娠期、哺乳期使用的安全性。方法查阅文献,以近几年国内外代表性的大型研究、指南为依据,进行分析、整理和归纳。结果早孕期暴露于抗甲状腺药物出生缺陷发生率增高,随访到2岁的大型研究显示,PTU暴露的儿童缺陷发生率8.0%,主要在面部和颈部有畸形。MMI/卡比马唑(carbimazole,CMZ)暴露的儿童缺陷发生率9.1%,常见鼻后孔闭锁、食管闭锁、脐疝、脐肠系膜管异常和发育不全。母亲孕早期MMI/CMZ向PTU转换的儿童缺陷发生率10.1%,主要与泌尿系统畸形相关。未暴露儿童缺陷发生率5.7%。致畸的高风险阶段在妊娠6~10周。哺乳期妇女服用中等剂量的PTU(<300 mg·d^(-1))或MMI(20~30 mg·d^(-1))都是安全的。结论 MMI和PTU与出生缺陷相关,但畸形谱不同。为减少婴儿的药物暴露量,抗甲状腺药物应分次在母乳喂养后服用。

OBJECTIVE To investigate the safety of methimazole（MMI）and propylthiouracil（PTU） in pregnancy and lactation. METHODS The literatures were reviewed and summarized based on the large-scale representative studies and guidelines in recent years. RESULTS Both MMI/carbimazole（CMZ） and PTU or shift between MMI/CMZ and PTU in early pregnancy were associated with an increased ration of birth defects. The prevalence of birth defects was high in children before 2 years old （PTU, 8.0%; MMI/CMZ, 9.1%; MMI/CMZ and PTU, 10.1%; nonexposed, 5.7%）. MMI/CMZ and PTU were associated with urinary system malformation, and PTU with malformations in the face and neck region. Choanal atresia, esophageal atresia, omphalocele, omphalomesenteric duct anomalies, and aplasia cutis were common in MMI/CMZ-exposed children. The relative high risk is confined to gestational weeks 6-10. MMI at doses up to 20-30 mg.d-1 was safe for lactating mothers and their infants. PTU at doses up to 300 mg·d-1 was a second-line agent due to concerns about severe hepato-toxicity. CONCLUSION Both MMI/CMZ and PTU are associated with birth defects, but the spectrum of malformations is different. Antithyroid drugs should be administrated following a feeding and in divided doses.