妊娠期药物致畸风险咨询技术规范

doi:10.3877/cma.j.issn.1673-5250.2021.04.004

中华妇幼临床医学杂志(电子版) ›› 2021, Vol. 17 ›› Issue (04) : 393 -401. doi: 10.3877/cma.j.issn.1673-5250.2021.04.004

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妊娠期药物致畸风险咨询技术规范

陶晶¹^,¹, 李小洪¹^,²^,¹^,², 谭曦³^,³, 陈力⁴^,⁴, 尹爱华⁵^,⁵, 王和⁶^,⁶, 赵扬玉⁷^,⁷, 杨勇⁸^,⁸, 张欣文⁹^,⁹, 张晓辉¹⁰^,¹⁰, 王雪燕¹¹^,¹¹, 陈敦金¹²^,¹², 杜娟¹³^,¹³, 陈素华¹⁴^,¹⁴, 蒋小青¹⁵^,¹⁵, 张国英¹⁵^,¹⁵, 李力¹⁶^,¹⁶, 张岩¹⁷^,¹⁷, 顾锦华¹⁸^,¹⁸, 李芬¹⁹^,¹⁹, 谢兰⁸^,⁸, 赵娟娟²⁰^,²⁰, 张春红²¹^,²¹, 朱军¹^,²^,^†^,¹^,²(

)

收稿日期:2021-03-22 修回日期:2021-07-19 出版日期:2021-08-01
通信作者: 朱军

Technical specification for consultation on the risk of drug teratogenicity during pregnancy

Jing Tao¹^,¹, Xiaohong Li¹^,²^,¹^,², Xi Tan³^,³, Li Chen⁴^,⁴, Aihua Yin⁵^,⁵, He Wang⁶^,⁶, Yangyu Zhao⁷^,⁷, Yong Yang⁸^,⁸, Xinwen Zhang⁹^,⁹, Xiaohui Zhang¹⁰^,¹⁰, Xueyan Wang¹¹^,¹¹, Dunjin Chen¹²^,¹², Juan Du¹³^,¹³, Suhua Chen¹⁴^,¹⁴, Xiaoqing Jiang¹⁵^,¹⁵, Guoying Zhang¹⁵^,¹⁵, Li Li¹⁶^,¹⁶, Yan Zhang¹⁷^,¹⁷, Jinhua Gu¹⁸^,¹⁸, Fen Li¹⁹^,¹⁹, Lan Xie⁸^,⁸, Juanjuan Zhao²⁰^,²⁰, Chunhong Zhang²¹^,²¹, Jun Zhu¹^,²^,¹^,²^,^†()

Received:2021-03-22 Revised:2021-07-19 Published:2021-08-01
Corresponding author: Jun Zhu
Supported by:
National Key Research and Development Program of China(2018YFC1002201); Key Project of Research and Development of Science and Technology Department of Sichuan Province(2019YFS0530)

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陶晶, 李小洪, 谭曦, 陈力, 尹爱华, 王和, 赵扬玉, 杨勇, 张欣文, 张晓辉, 王雪燕, 陈敦金, 杜娟, 陈素华, 蒋小青, 张国英, 李力, 张岩, 顾锦华, 李芬, 谢兰, 赵娟娟, 张春红, 朱军. 妊娠期药物致畸风险咨询技术规范[J/OL]. 中华妇幼临床医学杂志(电子版), 2021, 17(04): 393-401.

Jing Tao, Xiaohong Li, Xi Tan, Li Chen, Aihua Yin, He Wang, Yangyu Zhao, Yong Yang, Xinwen Zhang, Xiaohui Zhang, Xueyan Wang, Dunjin Chen, Juan Du, Suhua Chen, Xiaoqing Jiang, Guoying Zhang, Li Li, Yan Zhang, Jinhua Gu, Fen Li, Lan Xie, Juanjuan Zhao, Chunhong Zhang, Jun Zhu. Technical specification for consultation on the risk of drug teratogenicity during pregnancy[J/OL]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2021, 17(04): 393-401.

孕妇妊娠期用药不当可能具有导致胎儿发生畸形的风险。妊娠期药物致畸风险咨询服务在保障母胎用药安全、减少出生缺陷方面发挥重要作用。目前，我国部分医疗机构已开展妊娠期药物致畸风险咨询服务，但是尚未制定涉及该项服务的相关技术规范。四川大学华西第二医院全国妇幼卫生监测办公室/中国出生缺陷监测中心，联合国内多家三级甲等医疗机构的产科、儿科、药剂科等多学科专家，共同制定《妊娠期药物致畸风险咨询技术规范》。该技术规范规定了妊娠期药物致畸风险咨询服务的定义、原则、流程、服务方式等内容，旨在指导我国医疗机构规范开展该项咨询服务工作，提升服务水平，保障母胎用药安全。

关键词: 妊娠, 药物毒性, 畸形，药物性, 药物副反应报告系统, 指示性咨询

Improper use of drugs by pregnant women during pregnancy may lead to fetal malformations. Counseling service on the risk of drug teratogenicity during pregnancy plays an important role in ensuring the safety of maternal and fetal medication and reducing birth defects. At present, some medical institutions in China have carried out counseling service on the risk of drug teratogenicity during pregnancy, but there is no relevant technical specification of the service. The Technical Specification for Consultation on the Risk of Drug Teratogenicity During Pregnancy has been jointly formulated by National Office for Maternal and Child Health Surveillance of China/National Center for Birth Defects Monitoring of China and multidisciplinary experts in department of obstetrics, pediatrics, pharmacy, etc. from Grade 3A medical institutions in China. The technical specification stipulates the definition, principle, process and service mode of drug teratogenic risk consultation service during pregnancy, in order to guide China′s medical institutions to standardize the counseling service, improve the service level, and ensure the safety of maternal and fetal medication.

Key words: Pregnancy, Drug toxicity, Abnormalities, drug-induced, Adverse drug reaction reporting systems, Directive counseling

图1 妊娠期药物致畸风险咨询服务流程图

表1 孕妇妊娠期用药对不同发育阶段胚胎/胎儿的影响

药物暴露时孕妇孕龄	药物对胎儿发育影响
受精后2周内(细胞增殖早期)	致畸因子的影响是"全"或"无"，即导致自然流产或对胚胎无影响
受精后3~8周(胚胎器官分化发育期)	致畸高敏感期，胚胎最易受到致畸因子影响而发生器官形态异常，但是各器官组织对不同致畸因子的反应各异
受精后第9周直至分娩(胚胎功能发育期)	胎儿生长、器官发育、功能完善形成期，胎儿外生殖器、骨骼系统、神经系统仍继续分化，致畸因子可能对这些结构和功能造成影响

表1 孕妇妊娠期用药对不同发育阶段胚胎/胎儿的影响

药物暴露时孕妇孕龄	药物对胎儿发育影响
受精后2周内(细胞增殖早期)	致畸因子的影响是"全"或"无"，即导致自然流产或对胚胎无影响
受精后3~8周(胚胎器官分化发育期)	致畸高敏感期，胚胎最易受到致畸因子影响而发生器官形态异常，但是各器官组织对不同致畸因子的反应各异
受精后第9周直至分娩(胚胎功能发育期)	胎儿生长、器官发育、功能完善形成期，胎儿外生殖器、骨骼系统、神经系统仍继续分化，致畸因子可能对这些结构和功能造成影响

图2 不同发育阶段胚胎/胎儿药物暴露与畸形发生关系示意图

[1]	Fan H, Gilbert R, O′Callaghan F, et al. Associations between macrolide antibiotics prescribing during pregnancy and adverse child outcomes in the UK: population based cohort study[J]. BMJ, 2020, 368: m331. DOI: 10.1136/bmj.m331.
[2]	Patorno E, Huybrechts KF, Bateman BT, et al. Lithium use in pregnancy and the risk of cardiac malformations[J]. NEJM, 2017, 376(23): 2245-2254. DOI: 10.1056/NEJMoa1612222.
[3]	Thomsen AML, Liew Z, Riis AH, et al. Nitrosatable drug exposure during pregnancy and risk of stillbirth[J]. Pharmacoepidemiol Drug Saf, 2019, 28(9): 1204-1210. DOI: 10.1002/pds.4867.
[4]	Zhang J, Ung COL, Wagner AK, et al. Medication use during pregnancy in mainland China: a cross-sectional analysis of a national health insurance database[J]. Clin Epidemiol, 2019, 11: 1057-1065. DOI: 10.2147/CLEP.S230589.
[5]	Lacroix I, Damase-Michel C, Lapeyre-Mestre M, et al. Prescription of drugs during pregnancy in France[J]. Lancet, 2000, 356(9243): 1735-1736. DOI: 10.1016/S0140-6736(00)03209-8.
[6]	Daw JR, Mintzes B, Law MR, et al. Prescription drug use in pregnancy: a retrospective, population-based study in British Columbia, Canada (2001-2006)[J]. Clin Ther, 2012, 34(1): 239.e2-249.e2. DOI: 10.1016/j.clinthera.2011.11.025.
[7]	Lupattelli A, Spigset O, Twigg MJ, et al. Medication use in pregnancy: a cross-sectional, multinational web-based study[J]. BMJ Open, 2014, 4(2): e004365. DOI: 10.1136/bmjopen-2013-004365.
[8]	Li HT, Xue M, Hellerstein S, et al. Association of China′s universal two child policy with changes in births and birth related health factors: national, descriptive comparative study[J]. BMJ, 2019, 366: l4680. DOI: 10.1136/bmj.l4680.
[9]	赵扬玉，原鹏波，陈练. 二孩时代高龄产妇面临的问题[J]. 中国实用妇科与产科杂志，2020, 36(2): 97-100. DOI: 10.19538/j.fk2020020101.
[10]	Devkota R, Khan GM, Alam K, et al. Impacts of counseling on knowledge, attitude and practice of medication use during pregnancy[J]. BMC Pregnancy Childbirth, 2017, 17(1): 131. DOI: 10.1186/s12884-017-1316-6.
[11]	Schwarz EB, Parisi SM, Handler SM, et al. Counseling about medication-induced birth defects with clinical decision support in primary care[J]. J Womens Health (Larchmt), 2013, 22(10): 817-824. DOI: 10.1089/jwh.2013.4262.
[12]	Griffin BL, Stone RH, El-Ibiary SY, et al. Guide for drug selection during pregnancy and lactation: what pharmacists need to know for current practice[J]. Ann Pharmacother, 2018, 52(8): 810-818. DOI: 10.1177/1060028018764447.
[13]	Mosley JF, Smith LL, Dezan MD. An overview of upcoming changes in pregnancy and lactation labeling information[J]. Pharm Pract (Granada), 2015, 13(2): 605. DOI: 10.18549/pharmpract.2015.02.605.
[14]	夏东胜. 我国药品说明书孕妇及哺乳期妇女用药标示问题分析及风险控制建议[J]. 中国药物警戒，2015, 12(4): 211-218. DOI: 10.19803/j.1672-8629.2015.04.006.
[15]	中国医院协会药事专业委员会《医疗机构药学服务规范》编写组. 医疗机构药学服务规范[J]. 医药导报，2019, 38(12): 1535-1556. DOI: 10.3870/j.issn.1004-0781.2019.12.001.
[16]	罗晓芳，漆洪波. 如何保证孕周的准确性[J]. 中华围产医学杂志，2015, 18(5): 331-333. DOI: 10.3760/cma.j.issn.1007-9408.2015.05.002.
[17]	Zhao Y, Hebert MF, Venkataramanan R. Basic obstetric pharmacology[J]. Semin Perinatol, 2014, 38(8): 475-486. DOI: 10.1053/j.semperi.2014.08.011.
[18]	Syme MR, Paxton JW, Keelan JA. Drug transfer and metabolism by the human placenta[J]. Clin Pharmacokinet, 2004, 43(8): 487-514. DOI: 10.2165/00003088-200443080-00001.
[19]	杨勇，陈诚，刘心霞. 妊娠期药物在母体和胎儿的药动学特点与用药安全[J]. 医药导报，2017, 36(9): 951-955. DOI: 10.3870/j.issn.1004-0781.2017.09.001.
[20]	Paulzen M, Schoretsanitis G, Gründer G, et al. Pregnancy exposure to venlafaxine-therapeutic drug monitoring in maternal blood, amniotic fluid and umbilical cord blood and obstetrical outcomes[J]. J Affect Disord, 2020, 266: 578-584. DOI: 10.1016/j.jad.2020.02.010.
[21]	Buhimschi CS, Weiner CP. Medications in pregnancy and lactation: part 1. Teratology[J]. Obstet Gynecol, 2009, 113(1): 166-188. DOI: 10.1097/AOG.0b013e31818d6788.
[22]	Tomson T, Battino D, Bonizzoni E, et al. Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry[J]. Lancet Neurol, 2011, 10(7): 609-617. DOI: 10.1016/S1474-4422(11)70107-7.
[23]	McCance-Katz EF. Drug interactions associated with methadone, buprenorphine, cocaine, and HIV medications: implications for pregnant women[J]. Life Sci, 2011, 88(21-22): 953-958. DOI: 10.1016/j.lfs.2010.09.016.
[24]	刘亮，范贞. 以法律的角度看待药品说明书的临床应用[J]. 中国临床药理学杂志，2020, 36(4): 456-457, 461. DOI: 10.13699/j.cnki.1001-6821.2020.04.020.
[25]	陈耀龙，李幼平，杜亮，等. 医学研究中证据分级和推荐强度的演进[J]. 中国循证医学杂志，2008, 8(2): 127-133. DOI: 10.3969/j.issn.1672-2531.2008.02.012.
[26]	刘瀚旻，李胜利，朱军. 中国出生缺陷图谱[M]. 2版. 北京：人民卫生出版社，2021: 4.
[27]	Temming LA, Cahill AG, Riley LE. Clinical management of medications in pregnancy and lactation[J]. Am J Obstet Gynecol, 2016, 214(6): 698-702. DOI: 10.1016/j.ajog.2016.01.187.
[28]	Koren G, Berkovitch M, Ornoy A. Dose-dependent teratology in humans: clinical implications for prevention[J]. Pediatr Drugs, 2018, 20(4): 331-335. DOI: 10.1007/s40272-018-0294-0.
[29]	Ansari J, Carvalho B, Shafer SL, et al. CME pharmacokinetics and pharmacodynamics of drugs commonly used in pregnancy and parturition[J]. Anesth Analg, 2016, 122(3): 786-804. DOI: 10.1213/ANE.0000000000001143.
[30]	药品不良反应报告和监测管理办法——中华人民共和国卫生部令81号第81号[J]. 中国药物经济学，2011，7(5)：68-75.
[31]	国家卫生健康委员会，国家中医药管理局. 关于印发互联网诊疗管理办法(试行)等文件的通知[J]. 中华人民共和国国家卫生健康委员会公报，2018(7): 25-35.
[32]	Smith DA, Beaumont K, Maurer TS, et al. Relevance of half-life in drug design[J]. J Med Chemist, 2018, 61(10): 4273-4282. DOI: 10.1021/acs.jmedchem.7b00969.
[33]	王少华，王霞. 妇产科合理用药[M]. 2版. 北京：人民卫生出版社，2009: 9，37.
[34]	Hill MD, Abramson FP. The significance of plasma protein binding on the fetal/maternal distribution of drugs at steady-state[J]. Clini Pharmacokinet, 1988, 14(3): 156-170. DOI: 10.2165/00003088-198814030-00004.
[35]	Feldkamp ML, Carey JC, Byrne JLB, et al. Etiology and clinical presentation of birth defects: population based study[J]. BMJ, 2017, 357: j2249. DOI: 10.1136/bmj.j2249.

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Technical specification for consultation on the risk of drug teratogenicity during pregnancy

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Technical specification for consultation on the risk of drug teratogenicity during pregnancy