合并胎儿心脏病变的抗SSA抗体阳性孕妇的临床及实验室特征

doi:10.19723/j.issn.1671-167X.2023.06.015

摘要/Abstract

摘要：

目的: 探究合并胎儿心脏病变的抗干燥综合征相关抗原A(Sjögren’s-syndrome-related antigen A, SSA)抗体阳性孕妇的临床表现、实验室指征及药物特征。方法: 在2013年1月至2023年7月于北京大学人民医院就诊且最终确诊自身免疫病的孕妇中, 选择抗SSA抗体阳性且超声确诊胎儿心脏病变的患者作为病变组, 抗SSA抗体阳性且超声检查无胎儿心脏病变的患者作为对照组, 收集两组患者的临床、实验室及用药信息, 比较组间基线数据无差异后对其临床指标进行统计学分析。结果: 合并胎儿心脏病变的抗SSA抗体阳性患者共11例, 其中有先天性房室传导阻滞表现者共7例, 是最常见的胎儿心脏病变类型。病变组患者孕前确诊自身免疫病的比例显著低于对照组(P=0.032), 多因胎儿心脏病变首次进行相关免疫学检查。病变组患者孕期白细胞水平[(9.29±2.58)×10⁹/L vs. (7.10±1.90)×10⁹/L, t=3.052, P=0.004]、红细胞沉降率[49.50(48.00, 51.00) mm/h vs. 23.00(15.00, 30.25) mm/h, Z=-2.251, P=0.024]、IgA水平[3.46(2.30, 5.06) g/L vs. 2.13(1.77, 2.77) g/L, Z=-2.181, P=0.029]、抗核抗体(antinuclear antibody, ANA)滴度[1∶320(1∶160, 1∶320) vs. 1∶80(1∶40, 1∶160), Z=-3.022, P=0.003]显著高于对照组。组间孕期合并SSB抗体阳性的比例(37.5% vs. 7.7%, P=0.053)、羟氯喹使用剂量及起用时间差异均无统计学意义。病变组孕期使用激素的比例及剂量显著高于对照组(P＜0.05), 其中孕早期两组间差异无统计学意义, 而孕中期、孕晚期病变组激素使用剂量显著高于对照组。结论: 胎儿心脏病变是一种罕见但与抗SSA抗体阳性高度相关的胎儿畸形, 孕期白细胞、红细胞沉降率、IgA水平及ANA滴度显著升高的患者胎儿心脏病变发生的风险更高。胎儿房室传导阻滞一旦发生便难以逆转, 因此, 预防和监测的重要性高于补救治疗。

关键词: 抗SSA抗体, 先天性心脏缺损, 心脏传导阻滞, 妊娠, 危险因素

Abstract:

Objective: To investigate the clinical manifestations and laboratory indicators of anti-Sjögren's-syndrome-related antigen A (SSA) antibody associated fetal cardiac disease. Methods: Pregnant women hospitalized at Peking University People's Hospital from January 2013 to July 2023 were included. Eleven patients with anti-SSA antibody positive were eventually diagnosed with fetal cardiac di-sease. And patients with anti-SSA antibody positive without fetal cardiac disease were selected as controls. Clinical manifestations, laboratory indications and drug usage were compared between the two groups. Results: Among these 11 patients, congenital heart block was confirmed in seven, which was the most common manifestations of fetal cardiac malformation. The proportion of the patients diagnosed with autoimmune disease before pregnancy in fetal cardiac malformation group was significantly lower than that in the control group (P=0.032), while most of the patients in the fetal cardiac malformation group received immune-related examinations for the first time because of this time's fetal cardiac diagnosis. While most of the patients in the control group received routine examinations because of autoimmune diseases diagnosed before pregnancy. During pregnancy, the white blood cell level [(9.29±2.58)×10⁹/L vs. (7.10±1.90×10⁹/L, t=3.052, P=0.004], erythrocyte sedimentation rate [(49.50 (48.00, 51.00) mm/h vs. 23.00 (15.00, 30.25) mm/h, Z=-2.251, P=0.024], IgA level [3.46 (2.30, 5.06) g/L vs. 2.13 (1.77, 2.77) g/L, Z=-2.181, P=0.029], and antinuclear antibody (ANA) titers [1∶320 (1∶160, 1∶320) vs. 1∶80 (1∶40, 1∶160), Z=-3.022, P=0.003] were significantly higher in fetal cardiac malformation group than in the control group. The proportion of positive anti-SSB antibody during pregnancy did not show a statistically significant difference between the two groups (37.5% vs. 7.7%, P=0.053). There was no significant difference in hydroxychloroquine dosage and initiation time between the two groups. The dosage of prednisone in the second and third trimesters was significantly higher in the cardiac malformation group than that in the control group, but there was no significant difference in the first trimester. Conclusion: Fetal cardiac disease is rare in pregnant women with anti-SSA antibody. White blood cell, erythrocyte sedimentation rate, IgA, the titer of ANA positivity were higher in the fetal heart disease group during pregnancy. Since congenital heart block is difficult to reverse, its prevention and monitoring are more important than remedial treatment.

Key words: Anti-Sjögren's-syndrome-related antigen A antibody, Congenital heart defects, Heart block, Pregnancy, Risk factors

中图分类号:

R593.2

李宇菲,闫亚妮,靳家扬,李春,裴秋艳. 合并胎儿心脏病变的抗SSA抗体阳性孕妇的临床及实验室特征[J]. 北京大学学报（医学版）, 2023, 55(6): 1053-1057.

Yu-fei LI,Ya-ni YAN,Jia-yang JIN,Chun LI,Qiu-yan PEI. Clinical characteristics of fetal cardiac disease in patients with anti-SSA antibody positive[J]. Journal of Peking University (Health Sciences), 2023, 55(6): 1053-1057.

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Parameters	Cardiac malformation (n=11)	Control (n=44)	P
Clinical feature, n(%)
History of miscarriage	5 (45.5)	22 (50.0)	> 0.999
Leukopenia during pregnancy	0	7 (15.9)	0.323
Thrombocytopenia during pregnancy	2 (18.2)	10 (22.7)	> 0.999
Diagnosis of autoimmune disease before pregnancy	6 (54.5)	38 (86.4)	0.032
Complicating disease, n(%)
Hashimoto thyroiditis	2 (18.2)	2 (4.5)	0.175
Hyperthyroidism	0	0	> 0.999
Hypothyroidism	1 (9.1)	8 (18.2)	0.669
Gestational diabetes mellitus	1 (9.1)	3 (6.8)	> 0.999
Ovarian tumor	0	2 (4.5)	> 0.999

Parameters	Cardiac malformation (n=11)	Control (n=44)	Z/t/χ²	P
WBC during pregnancy/(×10⁹/L)	9.29±2.58	7.10±1.90	3.052	0.004
PLT during pregnancy/(×10⁹/L)	202.20±79.05	171.51±56.68	1.428	0.159
ESR during pregnancy/(mm/h)	49.50 (48.00, 51.00)	23.00 (15.00, 30.25)	-2.251	0.024
IgA during pregnancy/(g/L)	3.46 (2.30, 5.06)	2.13 (1.77, 2.77)	-2.181	0.029
ANA positive during pregnancy	10/10 (100.0)	38/40 (95.0)		> 0.999
ANA titer during pregnancy	1∶320 (1∶160, 1∶320)	1∶80 (1∶40, 1∶160)	-3.022	0.003
Anti-SSB positive during pregnancy	3/8 (37.5)	3/39 (7.7)		0.053

Parameters	Cardiac malformation (n=11)	Control (n=44)	Z/t/χ²	P
HCQ
Use of HCQ during pregnancy, n(%)	10 (90.9)	35 (79.5)		0.667
Use of HCQ during the first trimester, n(%)	6 (54.5)	33 (75.0)		0.266
HCQ dose in the first trimester/mg, M (P₂₅, P₇₅)	200 (0, 200)	200 (25, 200)	-1.117	0.264
HCQ dose in the second trimester/mg, M (P₂₅, P₇₅)	200 (200, 200)	200 (100, 200)	-0.555	0.579
HCQ dose in the third trimester/mg, M (P₂₅, P₇₅)	200 (200, 200)	200 (125, 200)	-1.098	0.272
Prednisone
Use of prednisone during pregnancy, n(%)	9 (81.8)	16 (36.4)		0.015
Prednisone dose in the first trimester/mg, M (P₂₅, P₇₅)	0 (0, 10.00)	0 (0, 5.00)	-0.593	0.553
Prednisone dose in the second trimester/mg, M (P₂₅, P₇₅)	10.00 (0, 20.00)	0 (0, 5.00)	-2.924	0.003
Prednisone dose in the third trimester/mg, M (P₂₅, P₇₅)	10.00 (5.00, 26.70)	0 (0, 5.00)	-3.347	0.001