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

doi:10.3877/cma.j.issn.1673-5250.2024.02.001

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
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	眼肌型	全身型	AChR抗体阳性^b
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
组别	例数	孕前QMG(分)^a	Ⅰ型	Ⅱ型	Ⅲ型	Ⅳ型	孕前发生MC	孕期采取治疗MG	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＝0.10^d
P值		0.049	0.455				0.600	0.020	0.752

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
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	眼肌型	全身型	AChR抗体阳性^b
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
组别	例数	孕前QMG(分)^a	Ⅰ型	Ⅱ型	Ⅲ型	Ⅳ型	孕前发生MC	孕期采取治疗MG	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＝0.10^d
P值		0.049	0.455				0.600	0.020	0.752

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