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引用本文:汪凤梅,王灵杰.妊娠期和哺乳期妇女抗甲状腺药物的安全性评价[J].中国现代应用药学,2017,34(12):1747-1750.
WANG Fengmei,WANG Lingjie.Evaluation the Safety of Methimazole and Propylthiouracil in Pregnancy and Lactation[J].Chin J Mod Appl Pharm(中国现代应用药学),2017,34(12):1747-1750.
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妊娠期和哺乳期妇女抗甲状腺药物的安全性评价
汪凤梅1, 王灵杰2
1.浙江大学医学院附属妇产科医院, 杭州 310006;2.浙江省嵊州市人民医院, 浙江 嵊州 312400
摘要:
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。
关键词:  抗甲状腺药物  丙基硫氧嘧啶  甲巯咪唑  妊娠期  哺乳期  安全性
DOI:10.13748/j.cnki.issn1007-7693.2017.12.023
分类号:R969.3
基金项目:浙江省人口计生委(JSW2013-A010)
Evaluation the Safety of Methimazole and Propylthiouracil in Pregnancy and Lactation
WANG Fengmei1, WANG Lingjie2
1.Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China;2.Shengzhou People's Hospital, Shengzhou 312400, China
Abstract:
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.
Key words:  antithyroid drugs  propylthiouracil  methimazole  pregnancy  lactation  safety
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