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指南速递 | ERS/TSANZ工作组声明:患有呼吸道疾病女性生殖和妊娠管理(上)

2020-12-17 14:55 来源: 中国妇产科网 作者: 中国妇产科网 浏览量: 6937

翻译:李乐谦1 余欣玥1 梁晶晶2 黄启涛3

(1. 南方医科大学第一临床医学院;2. 南方医科大学第二临床医学院;3. 南方医科大学南方医院妇产科)

审核:陈继明

(南京医科大学附属常州第二人民医院妇产科;南京医科大学常州临床医学院妇产科学教研室)

背景:该声明概述了有关治疗呼吸道疾病妇女生殖和妊娠的文献和专家意见。该声明是欧洲呼吸学会(ERS)和澳大利亚和新西兰胸科学会(TSANZ)为制定此类文件而开展的第一次合作。

该声明涵盖呼吸道疾病,即哮喘,囊性纤维化(CF)和非CF支气管扩张。现在,患有这些疾病的许多妇女正处于生育年龄,其中一些在成年早期发展为中度至严重的肺功能损害。该声明涵盖了生育,怀孕期间的管理,药物作用和分娩期间的问题。

该声明总结了当前的知识,但未提出推荐。该声明将不讨论怀孕期间发生的生理变化,例如气道生理,休息通气和睡眠的变化,这些变化已在其他地方进行了总结[1]。该声明将不涵盖其他形式的肺部疾病,例如肺纤维化,肺动脉高压,与胃食管反流相关的肺部疾病或尼古丁消耗问题。

方法:ERS / TSANZ工作队由呼吸科医生,妇产科医生,全科医生,专职医疗人员和患有呼吸道疾病的妇女组成。该工作队获得了ERS方法学家和欧洲肺基金会的支持,与患者志愿者合作,设计了一项在线调查表,以更好地了解妇女患上呼吸道疾病时的看法。所有合著者都严格审查并批准了最终声明,并完成了利益冲突表。

本ERS声明基于文献搜索和面对面会议,结合了基于证据的方法以及工作组成员的临床专业知识。使用了Medline,Embase和CINAHL数据库进行文献搜索,仅限1995年以后的英文文献。

两位主席(PM和VB)对文献检索的所有参考文献进行了审查,然后向选择相关文献的工作组成员提供了一些论文。分歧通过协商解决。选择的依据是人群(患有哮喘,CF或支气管扩张的孕妇)以及这些疾病对妊娠相关并发症和流产,母乳喂养,营养因素,肺功能,长期母体结局以及妊娠期间管理因素的影响。几乎没有随机对照试验(仅限于哮喘妇女的妊娠处理),因此证据包括观察性研究(前瞻性或回顾性),横断面调查和病例系列。最近出版的其他指南,可能对读者有所帮助[2]。当前的工作组建立在这些其他准则的基础上,但是NICE文件仅涉及产时护理,其中当前的文件限制了疾病类别(即哮喘,CF和支气管扩张),但涵盖了妊娠之前,期间和之后的问题。

本文档旨在提供文献和当前证据的概述,并未针对每个主题或临床实践建议提供全面的系统综述和荟萃分析。

患有呼吸道疾病的妇女的生殖和受孕问题

许多慢性呼吸道疾病在生命早期就开始出现,因此在试图怀孕的成年女性中也存在。尽管已发现哮喘女性的生育能力受损,但该领域的研究很少[3]。对于囊性纤维化(CF),年轻成年女性临床状态变化导致很难将较早的研究与更多现有文献进行对比,而对于支气管扩张则几乎没有可用的数据。

哮喘患者的生育能力

不同的研究发现,哮喘的存在与妇女生育能力低下之间有着不同的联系[3,5,6]。最近的研究表明哮喘会通过增加怀孕时间(TTP)和降低出生率而对生育产生负面影响[3,6]。哮喘妇女的TTP,尤其是在35岁以上[3],随着孕妇年龄的增加而增加,生育治疗的使用增加,这可能意味着疾病的严重程度或接触低级别炎症的时间对生育能力有负面影响。

试图阐明哮喘药物和潜在哮喘严重程度对生育能力的相对影响的流行病学数据尚无定论。Gade等[3] 尽管无法区分哮喘本身的严重程度和治疗水平[3],但发现未经治疗的哮喘(定义为无常规吸入器)与TTP之间存在关联,以及每日吸入皮质类固醇(ICS)与较长的TTP之间存在关联。然而,在随后的临床研究中并未发现这一点[7]。最近,来自SCOPE研究的有趣数据显示,仅使用短效β2激动剂(SABA)自我报告哮喘的妇女的TTP延长并生育力降低[6],而接受ICS处方的自我报告哮喘的妇女生育力却没有降低。这表明治疗哮喘合并系统性炎症可降低生育能力[6]。基于这些数据,应告知患有哮喘的女性生育能力可能降低的风险,尤其对于未采取ICS维持治疗以及年龄超过35岁的女性[7,8]。

CF和支气管扩张患者的生育力

由于改善了治疗方法,CF患者的预期寿命一直在延长[4,9],这就使越来越多的CF男女患者活到成年并且想生育。在这两种情况下,建议对伴侣进行CFTR突变测试,以进行有关产前测试和植入前遗传学诊断的适当讨论[10,11]。

众所周知,大多数(95%)患有CF的男性因输精管阻塞或没有输精管而不育,这就需要在怀孕时进行IVF干预[10]。相反,虽然囊性纤维化跨膜电导调节剂(CFTR)在子宫颈中表达,宫颈粘液的含水量不显示正常的月经周期变化,但大多数患有CF[13]的成年妇女输卵管仍然是开放的。患有CF的妇女的生育能力可能因营养不良而恶化,导致排卵不正常或继发闭经。最近的一项跨国调查显示,患有CF的妇女经历不孕的比例为35%,而一般人只有5-15%[14]。年龄大、胰功能不全与低生育力有关,而肺功能及BMI与低生育无关。正常生育妇女中CFRD阳性率为16%,低生育组为23%(p=0.02),而CFRD妇女尝试受孕的可能性明显低于正常生育妇女。在生育率下降的情况下,有必要采用体外受精[14]。最近,法国对2001至2012年间报告怀孕的CF妇女进行了一项登记研究,发现有14/29患有妊娠前糖尿病的妇女报告了医疗辅助怀孕情况,而没有CFRD的妇女中有51/160报告了医疗辅助怀孕的情况(p=0.06)[15]。

对于患有CF相关糖尿病(CFRD)的女性,预期良好的血糖控制能够提高受孕能力,并降低非CF糖尿病女性孕前保健中流产和先天性畸形的风险[16]。妊娠期糖尿病很常见,因此目前的指南建议对所有患有CF的孕妇在怀孕前和怀孕期间重复进行口服葡萄糖耐量试验(OGTT)[17-19]。

与之相对的是关于哮喘和CF生育问题的知识,由于其他原因,对支气管扩张的这些问题却知之甚少。通常,大多数临床医生将使用类似的方法来控制生育,以最大程度地提高肺功能和营养,并最大限度地减少慢性感染。

适用于所有部分的呼吸道药物概述:

持续使用吸入疗法对妊娠期呼吸道疾病的治疗至关重要。本节概述了针对不同呼吸道疾病的常用的药物及其对子宫,胎儿和母乳喂养的影响。没有对文献进行系统的审查,参考文献是由具有相关领域经验的临床药理学家根据其相关性和来自监管机构的产品信息选择的。

单个药物的完整详细信息,可通过澳大利亚治疗商品管理局(TGA)[20],欧洲药品管理局[21]和美国食品药品管理局[22]处获取。TGA对所有在怀孕和哺乳期使用的药物进行评级,并根据感知风险进行分类。应当指出,FDA的新《怀孕和哺乳标签规则》删除了怀孕字母类别(A,B,C,D和X),并提倡传达有关在怀孕和哺乳期使用药物的益处和风险的信息。为了完整起见,此处将其包括在内。

审校简介

陈继明,男,副主任医师,医学博士(在站博士后),硕士研究生导师。现任南京医科大学常州临床医学院妇产科学教研室主任,南京医科大学附属常州第二人民医院大妇科副主任兼妇科病区主任,南京医科大学附属常州第二人民医院阳湖院区临床第三党支部书记。主要专业特长为妇科内分泌疾病及妇科良恶性肿瘤的微创治疗,擅长经脐单孔腹腔镜手术(TU-LESS)及经阴道自然通道单孔腹腔镜手术(V-NOTES)。熟练掌握单孔腹腔镜下妇科良恶性肿瘤手术及单孔腹腔镜下深部子宫内膜异位症手术,并将5mm mini切口单孔腹腔镜手术广泛应用于妇科疾病的诊治。单孔腹腔镜技术曾获市医学新技术引进奖一等奖(2017),江苏省医学新技术引进奖二等奖(2019),院医学新技术引进奖二等奖(2019),第六届/第七届中国妇产科网手术视频大赛三等奖,第六届/第七届SESGE优秀手术视频奖,第六届妇科肿瘤长江论坛青年医师优秀视频二等奖,2018江苏抗癌协会妇科肿瘤年会视频比赛二等奖,第六届珠江论坛手术视频决赛优秀奖,第11届子宫内膜异位手术大赛——江苏区域赛冠军,全国总决赛季军等。

现任“中华预防医学会生育力保存分会生殖内分泌生育保护学组委员”、“中国医师协会妇产科分会妇科单孔腹腔镜技术全国科研协作组成员”、“中国成人教育协会继续医学教育委员会腔镜国际培训中心常务委员”、 “中国性科学理事会专家委员会委员” 、“中国中药协会女性生殖健康药物研究专业委员会委员”、 “中国中药协会真实世界研究专业委员会委员”、 “中国中医药研究促进会中西医结合妇产与妇幼保健分会委员”、 “中国医药教育协会毕业后与继续医学教育指导委员会委员”、“中国研究型医院学会妇科肿瘤专业委员会青年委员”、 “中国妇幼保健协会妇幼微创分会青年委员会全国青年委员”、 “中国老年医学学会妇科分会青年委员会委员”、“中国妇幼保健协会妇幼微创分会腹腔镜学组委员”、“中国妇幼保健协会妇科内分泌专业委员会青年科研学组秘书”、“中国妇幼保健协会妇科内分泌专业委员会妇科内分泌与肿瘤青年学组委员”、“中国妇幼保健协会妇科内分泌专业委员会健康扶贫工作学组委员”、 “中国医疗保健国际交流促进会妇产科分会妇产科创新技术与临床转化学组委员”、“中国整形美容协会女性生殖整复分会生殖物理整复专业学组成员”、“江苏省医学会妇科肿瘤学分会委员”、“江苏省医师协会妇产科医师分会委员”、“江苏省老年医学学会妇科分会常务委员”、“江苏省医师协会微无创医学专业委员会妇科学组委员”、“江苏省预防医学会妇女保健专业委员会女性盆底学组成员”、“江苏省预防医学会妇女保健专业委员会妇科内分泌学组成员”、“常州市医学会妇产科分会第五届委员会委员兼秘书”、“常州市医师协会妇产科医师分会第二届委员会委员兼秘书”、“同心.共铸中国心”妇产科专家委员会常州分会副主任委员、“美国妇科腹腔镜医师协会(AAGL)会员”。

获评"江苏省333人才工程第三层次培养对象"、“江苏省卫生拔尖人才”、“常州青年医学创新人才工程培养对象”、“2018常州市引进优秀医学博士”、“2019《健康报》社首批青年医生全明星成长计划”、“院十佳青年医务工作者”、“院十佳党员创新人才”、“院十佳患者信赖的医务工作者”、“常州市医学会先进个人”、“杏霖妇科内分泌研究院优秀科普讲者”等。

现为《中国计划生育与妇产科》、《国际妇产科前沿》、《现代药物与临床》等杂志编委;《药物评价研究》、《实用妇科内分泌》等杂志中青年编委、《Life Research》editor;《World Journal of Gynecology & Women’s Health》editor;《中国肿瘤外科》、《中国性科学》、《石河子大学学报(自然科学版)》、《重庆医学》、《安徽医药》等杂志特邀审稿专家。目前发表各类论文120余篇,其中SCI论文10余篇,教学论文10余篇。参译妇科专业书籍1部,副主编书籍1部,参编书籍2部。主持各类科研项目8项,曾获市医学新技术引进奖一等奖1项,江苏省医学新技术引进奖二等奖1项,院医学新技术二等奖1项,在全国各类病例演讲/科普演讲/论文演讲/手术视频演讲等比赛中荣获冠军/亚军/季军及优秀奖等共计30余项/次。

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