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Interpretation on the 2022 Chinese Guideline for the Management of Pregnancy and Reproduction in Patients with Systemic Lupus Erythematous
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摘要: 系统性红斑狼疮(systemic lupus erythematosus，SLE)多发于育龄期女性，其生育管理已成为SLE患者疾病管理的重要内容。在国家皮肤与免疫疾病临床医学研究中心、国家妇产疾病临床医学研究中心、中国系统性红斑狼疮研究协作组、中国风湿免疫病相关生殖及妊娠研究委员会的联合组织与指导下，制定了我国首部系统性红斑狼疮患者生殖与妊娠管理指南。该指南针对13个亟待解决的临床问题作出基于循证证据的推荐，涵盖了孕前准备(孕前咨询、妊娠风险评估、妊娠时机选择、辅助生育措施选择)、妊娠期疾病监测与治疗、胎儿监测与并发症诊治、产后随访与哺乳注意事项及新生儿监护的母婴全程管理，指南还就SLE患者妊娠的适应证、禁忌证、妊娠过程中一些重要脏器损害的识别与治疗、妊娠与哺乳期药物的使用、妊娠终止的适应证与围妊娠终止期药物的调整、合并抗磷脂抗体综合征患者的诊治等临床关心的重大问题作出了详细推荐，旨在提高SLE患者的妊娠成功率，降低母婴病死率。Abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease most prevalent in child-bearing young women. With the progress of treatment, the survival rate of SLE patients has been remarkably improved. Reproduction management of SLE patients has become one of the most important parts of SLE patients management. However, due to the complicated inter-reaction between SLE disease and the related concurrent problems, reproduction management of SLE patients remains a big challenge. Led and guided by the National Clinical Research Center for Dermatologic and Immunologic Diseases, the National Clinical Research Center for Obstetrics and Gynecology, Chinese Systemic Lupus Erythematosus Treatment and Research Group and Chinese Research Committee of Pregnancy and Reproduction in Autoimmune Rheumatic Diseases, the first guideline dedicated to the management of pregnancy and reproduction in patients with systemic lupus erythematous has been developed. This guideline is composed of 13 evidence-based recommendations, including pre-pregnant preparation (pre-pregnant consultation, risk assessment, indications and contraindications for pregnancy and the choices of assisted reproduction technology), monitoring and treatment strategy during pregnancy, monitoring and complications identification and management of the fetus, and recommendations for disease follow-up after delivery and feeding of the neonates. These recommendations, covering the whole process of pregnancy of SLE patients, are aimed to improve the success rate of pregnancy of SLE patients and decrease the morbidity and mortality of SLE patients and their fetus.
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Key words:
- systemic lupus erythematosus /
- reproduction /
- pregnancy /
- guideline /
- interpretation
作者贡献：田新平、赵久良、李梦涛、宋亦军、刘俊涛负责文献查阅、资料收集及论文撰写；曾小峰负责组织选题及论文审校。利益冲突：所有作者均声明不存在利益冲突 -
表 1 SLE患者妊娠期随访频率和随访内容
孕周 随访频率 随访内容 风湿免疫科 产科 孕4~10周 每4周1次 血常规、肝肾功能、凝血、补体、甲状腺功能、ANA、抗dsDNA抗体、抗SSA抗体、抗SSB抗体、抗磷脂抗体谱、尿常规+沉渣、24 h尿蛋白、心电图、超声心动图 (1)HIV、HBV、HCV、TORCH
(2)早孕超声确认妊娠
(3)建立产科档案
(4)确认预产期
(5)测量基线BP、体质量孕10~16周 每4周1次 SLE妊娠病情评估量表 孕11~14周进行妊娠期母体血清学筛查或无创胎儿游离DNA检测及超声NT检测 孕16~28周 每4周1次 (1)SLE妊娠病情评估量表
(2)抗SSA和/或抗SSB抗体阳性患者条件允许情况下, 建议孕16周开始每1~2周监测胎儿心脏超声，评估有无胎儿心脏异常(1)孕24~28周筛查妊娠期糖尿病
(2)记录胎心率
(3)孕18~24周彩色多普勒超声胎儿畸形筛查孕28~34周 每2周1次 SLE妊娠病情评估量表 (1)每2周进行彩色多普勒超声检查，评估胎儿脐动脉、子宫动脉、胎儿静脉导管、胎儿大脑中动脉
(2)筛查FGR
(3)根据母亲(高血压、抗凝治疗情况)和胎儿情况决定分娩方式
(4)进行临产和分娩准备相关宣教孕34周~分娩 每周1次 SLE妊娠病情评估量表 同孕28~34周 分娩后~产后6个月 每1~3个月1次 (1)SLE疾病活动评估量表
(2)静脉血栓预防(1)哺乳宣教
(2)产后康复锻炼SLE：系统性红斑狼疮；ANA：抗核抗体；HIV：人类免疫缺陷病毒；HBV：乙型肝炎病毒；HCV；丙型肝炎病毒；FGR：胎儿宫内生长受限 
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表 2 SLE患者妊娠期和哺乳期药物应用
药物 孕前 妊娠期 哺乳期 糖皮质激素 可用 现有证据未提示增加致畸风险；妊娠期应维持最小有效剂量 可用，应维持最小有效剂量；如剂量＞20 mg/d，须在服药后4 h内避免哺乳并将乳汁弃去，以减少婴儿暴露 羟氯喹 可用 现有证据未提示增加致畸风险，整个妊娠期均可应用 少量进入乳汁，但并未损害婴儿 硫唑嘌呤 可用 现有证据未提示增加致畸风险，整个妊娠期均可应用，最大剂量为2 mg/(kg·d) 可用 环孢素A 可用 现有证据未提示增加致畸风险，整个妊娠期均可应用，且应用最小有效剂量 可用 他克莫司 可用 现有证据未提示增加致畸风险，整个妊娠期均可应用，且应用最小有效剂量 可用 甲氨蝶呤 孕前须停用至少3个月 存在致畸风险，禁用 避免应用 环磷酰胺 存在明确致畸风险，孕前须停用3个月 存在致畸风险，禁用 避免应用 吗替麦考酚酯 存在明确致畸风险，孕前须停用3个月 存在致畸风险，禁用 避免应用 来氟米特 存在明确致畸风险，由于可经肝肠循环被再吸收入血，建议应用消胆胺(8 g，3次/d，连续11 d)清除后，停用6个月 存在致畸风险，禁用 避免应用 柳氮磺吡啶 可用 现有证据未提示增加致畸风险，每日最大剂量2 g，需补充叶酸5 mg/d 哺乳期可用，每日最大剂量2 g，须补充叶酸5 mg/d，以避免婴儿叶酸缺乏；由于早产儿可能存在G6PD缺乏，或有明确G6PD缺乏的新生儿，建议避免应用 IVIG 可用 可用 可用 利妥昔单抗 可用 现有证据未提示增加致畸风险，特殊情况下孕早期可应用；孕中晚期避免应用，以防导致胎儿B细胞缺乏等风险 避免应用 贝利尤单抗 可用 现有证据未提示增加致畸风险，但证据有限，建议妊娠期停用 避免应用 SLE：同表 1；IVIG：静脉注射用人免疫球蛋白；G6PD：6-磷酸葡萄糖脱氢酶
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