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中华妇幼临床医学杂志(电子版)

中华妇幼临床医学杂志(电子版) ›› 2024, Vol. 20 ›› Issue (02) : 125 -132. doi: 10.3877/cma.j.issn.1673-5250.2024.02.001

妊娠合并症专辑

妊娠合并重症肌无力患者的围产结局和重症肌无力病情恶化的影响因素分析
林雪1, 陈锰2, 杨梅琳3, 刘兴会2, 周红雨1,†()   
  1. 1. 四川大学华西医院神经内科，成都　610041
    2. 四川大学华西第二医院妇产科，成都　610041
    3. 厦门大学附属妇女儿童医院妇产科，厦门　361003
  • 收稿日期:2024-02-08 修回日期:2024-03-12 出版日期:2024-04-01
  • 通信作者: 周红雨

Perinatal outcomes of pregnant women with myasthenia gravis and risk factors for disease exacerbation of myasthenia gravis

Xue Lin1, Meng Chen2, Meilin Yang3, Xinghui Liu2, Hongyu Zhou1,†()   

  1. 1. Department of Neurology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
    2. Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
    3. Department of Obstetrics and Gynecology, Women′s and Children′s Hospital, Xiamen University, Xiamen 361003, Fujian Province, China
  • Received:2024-02-08 Revised:2024-03-12 Published:2024-04-01
  • Corresponding author: Hongyu Zhou
  • Supported by:
    Key Research and Development Project of Science & Technology Department of Sichuan Province(2022YFS0315)
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引用本文：

林雪, 陈锰, 杨梅琳, 刘兴会, 周红雨. 妊娠合并重症肌无力患者的围产结局和重症肌无力病情恶化的影响因素分析[J]. 中华妇幼临床医学杂志(电子版), 2024, 20(02): 125-132.

Xue Lin, Meng Chen, Meilin Yang, Xinghui Liu, Hongyu Zhou. Perinatal outcomes of pregnant women with myasthenia gravis and risk factors for disease exacerbation of myasthenia gravis[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2024, 20(02): 125-132.

目的

探讨妊娠合并重症肌无力(MG)患者的围产结局及导致其孕期及产褥期MG病情恶化影响因素。

方法

选择2015年1月至2023年12月在四川大学华西第二医院或厦门大学附属妇女儿童医院分娩的35例妊娠合并MG患者为研究对象。这35例患者，共计妊娠71次，其中活产为39次。根据35例妊娠合并MG患者39次活产中，该病是否导致患者孕期及产褥期MG病情恶化，将其分别纳入恶化组[n＝6，孕期及产褥期MG病情加重或发生肌无力危象(MC)]与稳定组(n＝33，孕期及产褥期MG病情稳定)。对于有≥2次妊娠的患者，进行分组与数据分析时，每次妊娠作为1例患者进行处理。采用回顾性分析方法，收集所有患者临床特征、妊娠经过、围产结局及MG病情转归等临床资料，并采用成组t检验或Mann-Whitney U检验或Fisher确切概率法，对2组患者临床资料进行比较，分析导致妊娠合并MG患者孕期与产褥期发生MG病情恶化的潜在危险因素。本研究通过四川大学华西医院医学伦理委员会审批(伦理号：2019-536)。

结果

①本研究35例妊娠合并MG患者39次活产中，3例为双胎，活产儿为42例。39次活产中，该病导致孕期及产褥期MG病情加重者为4例(10.3%)，发生MC者为2例(5.1%)，其余33例(84.6%)孕期及产褥期MG病情均平稳，无严重产科并发症发生；分娩孕龄为(38.5±2.4)孕周。其中，7例(17.9%)发生早产，28例(71.8%)为剖宫产术分娩，10例(10.3%)产后转重症监护病房(ICU)。分娩的42例新生儿中，2例(4.8%)发生新生儿一过性MG(TNMG)，8例(19.0%)转新生儿ICU(NICU)，无围产儿死亡者。②恶化组患者孕前MG定量评分(QMG)和孕期需要使用药物治疗MG者占比分别为10.5分(6.5分，16.0分)与100.0%(6/6)，均显著高于稳定组的6.0分(4.0分，8.0分)与45.5%(15/33)，并且差异均有统计学意义(Z＝－1.97、P＝0.049，P＝0.020)。

结论

妊娠合并MG患者孕期及产褥期MG病情多平稳，并且围产结局良好。但是，孕前QMG高和孕期需要采取药物控制MG病情者发生疾病恶化风险增加，临床应尤其重视此类孕妇的孕期及产褥期管理。

关键词: 重症肌无力, 妊娠, 围产结局, 疾病恶化, 危险因素, 孕妇
Objective

To investigate the perinatal outcomes of pregnant women with myasthenia gravis (MG) and risk factors leading to disease exacerbation of MG during pregnancy and puerperium.

Methods

A total of 35 pregnant women with MG in West China Second University Hospital, Sichuan University and Women′s and Children′s Hospital, Xiamen University from January 2015 to December 2023 was selected as research subjects. These 35 patients had a total of 71 pregnancies, of which 39 were live births. These 39 live births were divided into two groups: deterioration group [n=6, with a worsened MG or myasthenic crisis (MC) during pregnancy and puerperium] and stable group (n=33, with a stable MG during pregnancy and puerperium). For patients with ≥ 2 pregnancies, each pregnancy was considered as one case when grouping and data analysis. Clinical characteristics, pregnancy courses, perinatal outcomes, and MG prognosis were retrospectively collected and analyzed. Independent-samples t test or Mann-Whitney U test or Fisher′s exact test was used to explore the potential risk factors for MG exacerbation. This study was approved by the Medical Ethics Committee of West China Hospital, Sichuan University (Ethics No. 2019-536).

Results

①Among the 35 pregnant women with MG, including 39 cases of live birth, 3 cases of twin pregnancies and 42 neonates. Among the 39 cases of live birth, 4 cases (10.3%) experienced a worsened MG during pregnancy and puerperium, 2 cases (5.1%) developed MC, and the remaining 33 cases (84.6%) had a stable MG during pregnancy and puerperium. No serious obstetrical complications occurred. The gestational age of delivery was (38.5±2.4) gestational weeks. Preterm birth occurred in 7 cases (17.9%). 28 cases (71.8%) were delivered by cesarean section. 10 cases (10.3%) were admitted to intensive care unit (ICU) after delivery. 2 (4.8%) of the 42 neonates experienced transient neonatal MG (TNMG), and 8 neonates (19.0%) were admitted to neonatal ICU (NICU) after birth. There was no perinatal death. ②The quantitative MG (QMG) score before pregnancy and the proportion of patients needing for medication to treat MG during pregnancy in deterioration group were 10.5 points (6.5 points, 16.0 points) and 100.0% (6/6), respectively, which were both significantly higher than those 6.0 points (4.0 points, 8.0 points) and 45.5% (15/33) in stable group (Z=-1.97, P=0.049; P=0.020).

Conclusions

Most pregnant women with MG could have a stable condition during pregnancy and puerperium and have good perinatal outcomes. However, those with a high QMG score before pregnancy or need medication to control MG during pregnancy and puerperium have an increased risk of disease exacerbation of MG, thus special attention should be paid to the pregnancy and puerperium management of these patients by clinicians.

Key words: Myasthenia gravis, Pregnancy, Perinatal outcomes, Disease progression, Risk factors, Pregnant women
表1 本研究35例妊娠合并MG患者(39次活产)临床资料比较[例数(%)]
临床指标 发生率 临床指标 发生率
胸腺瘤病史 5(12.8) MuSK抗体阳性a 0(0)
胸腺切除术 14(35.9) 孕前MGFA临床分型a  
既往发生MC 3(7.7) Ⅰ型 4(30.8)
辅助生殖技术助孕 1(2.6) Ⅱ型 1(7.7)
双胎 3(7.7) Ⅲ型 5(38.4)
MG类型   Ⅳ型 3(23.1)
眼肌型 19(48.7) 孕期MG治疗 21(53.8)
全身型 20(51.3) 溴吡斯的明 13(33.3)
妊娠并发症与合并症   泼尼松 13(33.3)
妊娠期高血压疾病 3(7.7) 他克莫司 3(7.7)
妊娠期糖尿病 6(15.4) 硫唑嘌呤 2(5.1)
胎膜早破 10(25.6) 环孢素 0(0)
甲状腺功能减退症 7(17.9) 血浆置换 0(0)
甲状腺功能亢进症 6(15.4) 免疫球蛋白 2(5.1)
AChR抗体阳性a 10(76.9) 利妥昔单抗 0(0)
表2 本研究35例妊娠合并MG患者(39次活产)及其分娩新生儿结局[例数(%)或±s]
结局指标 发生率或数值 结局指标 发生率或数值 结局指标 发生率或数值
孕期及产褥期MG病情   剖宫产术分娩指征b   分娩孕龄(周) 38.5±2.4
稳定 33(84.6) 以MG为指征 12(42.8) 早产 7(17.9)
加重 4(10.3) 既往剖宫产术 7(25.0) 新生儿情况c  
MC 2(5.1) 双胎 3(10.7) 性别  
分娩方式   巨大儿 1(3.6) 男 20(47.6)
阴道分娩 11(28.2) 胎儿窘迫 1(3.6) 女 22(52.4)
剖宫产术分娩 28(71.8) 胎头下降停滞 1(3.6) 出生体重(g) 2 969±540
阴道分娩情况a   脐带绕颈2周 1(3.6) 窒息 0(0)
催产 1(9.1) 重度子痫前期 1(3.6) TNMG 2(4.8)
产程时间(h) 8.1±5.1 催产失败 1(3.6) 黄疸 7(16.7)
分娩镇痛 3(27.3) 麻醉方式b   入住NICU 8(19.0)
围产期并发症   硬膜外麻醉 4(14.3) 机械通气 1(2.4)
产后出血 0(0) 腰-硬联合麻醉 20(71.4) 先天畸形 2(4.8)
入住ICU 4(10.3) 全身麻醉 4(14.3) 死亡 0(0)
表3 恶化组与稳定组妊娠合并MG患者相关临床资料比较[±s或M(Q1，Q3)或例数(%)]
组别 例数 分娩时年龄(岁) 孕前BMI(kg/m2) 孕期体重增加值(kg) MG发病年龄(岁) 妊娠时MG病程(年) 首次妊娠年龄(岁) 辅助生殖技术助孕 双胎妊娠 妊娠期高血压疾病
恶化组 6 31.2±3.3 22.2±2.5 9.3±5.3 26.0(18.8，29.8) 4.2(1.2，14.5) 27.7±6.1 0(0) 0(0) 1(16.7)
稳定组 33 31.2±3.9 21.2±3.3 12.7±4.7 22.0(8.0，25.0) 10.1(6.0，22.0) 27.7±4.9 1(3.0) 3(9.1) 2(6.1)
统计量   t＝－0.01 t＝－0.71 t＝1.57 Z＝－1.66 Z＝－1.88 t＝0.02 －a －a －a
P值   0.999 0.412 0.137 0.097 0.062 0.985 0.850 0.600 0.350
组别 例数 妊娠期糖尿病 胎膜早破 甲状腺功能减退症 甲状腺功能亢进症 胸腺瘤 胸腺切除术 MG类型 AChR抗体阳性b
眼肌型 全身型
恶化组 6 0(0) 1(16.7) 1(16.7) 0(0) 0(0) 1(16.7) 1(16.7) 5(83.3) 3(75.0)
稳定组 33 6(18.2) 9(27.3) 6(18.2) 6(18.2) 5(15.2) 13(39.4) 18(54.5) 15(45.5) 7(77.8)
统计量   －a －a －a －a －a －a －a －a
P值   0.340 0.360 0.430 0.340 0.410 0.230 0.090 0.706
组别 例数 孕前QMG(分)a 孕前MGFA分型b 孕前发生MC 孕期采取治疗MG 新生儿性别c
Ⅰ型 Ⅱ型 Ⅲ型 Ⅳ型 男 女
恶化组 6 10.5(6.5，16.0) 1(25.0) 0(0) 3(75.0) 0(0) 0(0) 6(100.0) 2(33.3) 4(66.7)
稳定组 33 6.0(4.0，8.0) 3(33.3) 1(11.1) 2(22.2) 3(33.3) 3(9.1) 15(45.5) 18(50.0) 18(50.0)
统计量   Z＝－1.97 －a －a －a χ2＝0.10d
P值   0.049 0.455 0.600 0.020 0.752
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