系统性红斑狼疮患者不良妊娠结局的预测因素

doi:10.19723/j.issn.1671-167X.2025.03.026

摘要/Abstract

摘要：

目的: 探讨系统性红斑狼疮(systematic lupus erythematosus, SLE)不良妊娠结局(adverse pregnancy outcomes, APOs)的预测因素。方法: 回顾性分析2016年5月至2021年9月于北京大学人民医院产科住院分娩的SLE患者318例，根据患者是否存在APOs分为APOs组85例和非APOs组233例，分析SLE患者的病程、临床表现、实验室指标和疾病活动度(systematic lupus erythematosus disease activity index 2000, SLEDAI-2000)对妊娠结局的影响。结果: (1) SLE的平均发病年龄为(24.65±5.26)岁。在318次妊娠中，娩出302个活产婴儿(302/318, 94.97%)，16例(16/318, 5.03%)死胎，无新生儿死亡；活产婴儿中有足月儿206例(206/302, 68.21%)，小于胎龄儿(small for gestational age infant, SGA)65例(65/302, 21.52%)，早产儿31例(31/302, 10.26%)。(2)APOs组SLEDAI-2000评分显著高于非APOs组(5.82±4.97 vs. 3.74±3.72, t=4.019, P=0.001)。(3)APOs组糖皮质激素用量高于非APOs组[12.50 (7.50, 50.00) mg vs. 10.00 (5.00, 15.00) mg, P < 0.001]。(4)单因素分析显示，狼疮性肾炎(31.76% vs. 21.03%, χ²=3.946, P=0.047)、血小板减少(24.71% vs. 9.01%, χ²=13.380, P < 0.001)、低补体血症(36.47% vs. 26.03%, χ²=4.847, P=0.028)、抗磷脂抗体阳性(20.00% vs. 11.16%, χ²=4.163, P=0.041)和妊娠期未接受治疗(21.18% vs. 11.59%, χ²=4.713, P=0.030)与SLE患者发生APOs相关。在多因素分析中，低补体血症(OR=1.935, 95%CI: 1.104~3.393, P=0.021)、血小板减少(OR=2.671, 95%CI: 1.309~5.449, P=0.007)及抗磷脂抗体阳性(OR=2.153, 95%CI: 1.054~4.399, P=0.035)是SLE患者发生不良妊娠结局的独立危险因素。结论: 血小板减少、低补体血症及抗磷脂抗体阳性可以预测SLE患者APOs的发生，对指导SLE患者计划妊娠具有重要意义。

关键词: 系统性红斑狼疮, 不良妊娠结局, 预测因素

Abstract:

Objective: To identify predictors of adverse pregnancy outcomes (APOs) in patients with systemic lupus erythematosus (SLE). Methods: A retrospective analysis was conducted on 318 SLE patients who delivered at Peking University People' s Hospital from May 2016 to September 2021. These patients were categorized into two groups The APOs group (n=85) and the non-APOs group (n=233). Various factors, including disease duration, clinical manifestations, laboratory parameters, and systemic lupus erythematosus disease activity index 2000 (SLEDAI-2000) scores, were analyzed for their association with APOs. SPSS 26.0 software was used to analyze the data. Results: The mean age of SLE patients in this study was (24.65±5.26) years. Among the 318 pregnancies studied, 302 (302/318, 94.97%) resulted in live births, while 16 (16/318, 5.03%) cases ended in stillbirths, with no neonatal deaths reported. Among the live births, 206 (206/302, 68.21%) were full-term infants, 65 (65/302, 21.52%) cases were small for gestational age (SGA), and 31 (31/302, 10.26%) cases were preterm. The SLEDAI-2000 scores were significantly higher in the APOs group compared with the non-APOs group (5.82±4.97 vs. 3.74±3.72, t=4.019, P=0.001), suggesting greater disease activity as a risk factor. Similarly, glucocorticoid doses were markedly higher in the APOs group [12.50 (7.50, 50.00) mg vs. 10.00 (5.00, 15.00) mg, P < 0.001], underscoring the link between disease severity and APOs. Univariate analysis revealed that lupus nephritis (31.76% vs. 21.03%, χ²=3.946, P=0.047), thrombocytopenia (24.71% vs. 9.01%, χ²=13.380, P < 0.001), hypocomplementemia (36.47% vs. 26.03%, χ²=4.847, P=0.028), antiphospholipid antibody positivity (20.00% vs. 11.16%, χ²=4.163, P=0.041), and absence of pregnancy treatment (21.18% vs. 11.59%, χ²=4.713, P=0.030) were associated with increased APOs risk. Multivariate Logistic regression identified thrombocytopenia (OR=2.671, 95%CI 1.309-5.449, P=0.007), hypocomplementemia (OR=1.935, 95%CI 1.104-3.393, P=0.021), and antiphospholipid antibody positivity (OR=2.153, 95%CI 1.054-4.399, P=0.035) as independent predictors of APOs. Conclusion: These findings highlight that certain clinical and laboratory features, including thrombocytopenia, hypocomplementemia, and antiphospholipid antibody positivity, are critical independent predictors of APOs in SLE patients. The study underscores the importance of close monitoring and proactive management of these risk factors to improve pregnancy outcomes in SLE patients.

Key words: Systemic Lupus Erythematosus, Adverse pregnancy outcomes, Predictors

中图分类号:

R593.2

王文琼, 侯玉珂, 李春, 张学武. 系统性红斑狼疮患者不良妊娠结局的预测因素[J]. 北京大学学报（医学版）, 2025, 57(3): 599-603.

Wenqiong WANG, Yuke HOU, Chun LI, Xuewu ZHANG. Predictors of adverse pregnancy outcomes in patients with systemic lupus erythematosus[J]. Journal of Peking University (Health Sciences), 2025, 57(3): 599-603.

图/表 1

表1

参考文献 31

1	Petri M . Pregnancy and systemic lupus erythematosus[J]. Best Pract Res Clin Obstet Gynaecol, 2020, 64 (3): 24- 30.
2	中国系统性红斑狼疮研究协作组专家组, 国家风湿病数据中心. 中国系统性红斑狼疮患者围产期管理建议[J]. 中华医学杂志, 2015, 95 (14): 1056- 1060. doi: 10.3760/cma.j.issn.0376-2491.2015.14.005
3	张学武. 系统性红斑狼疮患者的妊娠及用药[J]. 中国临床医生杂志, 2015, 43 (7): 19- 21. doi: 10.3969/j.issn.2095-8552.2015.07.007
4	Hamijoyo L , Martha JW , Hidayat S , et al. Risk factors for poor pregnancy outcome in systemic lupus erythematosus patients[J]. Acta medica Indonesiana, 2019, 51 (2): 102- 109.
5	Nakai T , Kitada A , Fukui S , et al. Risk of adverse pregnancy outcomes in Japanese systemic lupus erythematosus patients with prior severe organ manifestations: A single-center retrospective analysis[J]. Lupus, 2021, 30 (9): 1415- 1426. doi: 10.1177/09612033211016074
6	Fava A , Petri M . Systemic lupus erythematosus: Diagnosis and clinical management[J]. J Autoimmun, 2019, 96 (1): 1- 13.
7	Yelnik CM , Laskin CA , Porter TF , et al. Lupus anticoagulant is the main predictor of adverse pregnancy outcomes in aPL-positive patients: Validation of PROMISSE study results[J]. Lupus Sci Med, 2016, 3 (1): e000131. doi: 10.1136/lupus-2015-000131
8	Kim MY , Buyon JP , Guerra MM , et al. Angiogenic factor imba-lance early in pregnancy predicts adverse outcomes in patients with lupus and antiphospholipid antibodies: results of the PROMISSE study[J]. Am J Obstet Gynecol, 2016, 214 (1): 108.e1- 108.e14. doi: 10.1016/j.ajog.2015.09.066
9	Kaul A , Gordon C , Crow MK , et al. Systemic lupus erythematosus[J]. Nat Rev Dis Primers, 2016, 2, 16039. doi: 10.1038/nrdp.2016.39
10	Velo-García A , Castro SG , Isenberg DA . The diagnosis and management of the haematologic manifestations of lupus[J]. J Autoimmun, 2016, 74 (9): 139- 160.
11	Artım-Esen B , Çene E , Șahinkaya Y , et al. Autoimmune haemolytic anaemia and thrombocytopaenia in a single-centre cohort of patients with systemic lupus erythematosus from Turkey: Clinical associations and effect on disease damage and survival[J]. Lupus, 2019, 28 (12): 1480- 1487. doi: 10.1177/0961203319877245
12	Shi H , Chen L , Wang Y , et al. Severity of anemia during pregnancy and adverse maternal and fetal outcomes[J]. JAMA Netw Open, 2022, 5 (2): e2147046. doi: 10.1001/jamanetworkopen.2021.47046
13	Lin L , Wei Y , Zhu W , et al. Prevalence, risk factors and associated adverse pregnancy outcomes of anaemia in Chinese pregnant women: A multicentre retrospective study[J]. BMC Pregnancy Childbirth, 2018, 18 (1): 111. doi: 10.1186/s12884-018-1739-8
14	Venkatachala RP , Sheela CN , Anandram S , et al. Autoimmune hemolytic anaemias in pregnancy: Experience in a Tertiary Care Hospital in South India[J]. J Obstet Gynaecol India, 2021, 71 (4): 379- 385. doi: 10.1007/s13224-021-01443-8
15	Laužikien D , Ramašauskait D , Lūža T , et al. Pregnancy induced autoimmune warm antibodies hemolytic anemia: A case report[J]. Geburtshilfe Frauenheilkd, 2015, 75 (11): 1167- 1171. doi: 10.1055/s-0035-1558131
16	Chapin J , Terry HS , Kleinert D , et al. The role of complement activation in thrombosis and hemolytic anemias[J]. Transfus Apher Sci, 2016, 54 (2): 191- 198. doi: 10.1016/j.transci.2016.04.008
17	Thornton P , Douglas J . Coagulation in pregnancy[J]. Best Pract Res Clin Obstet Gynaecol, 2010, 24 (3): 339- 352. doi: 10.1016/j.bpobgyn.2009.11.010
18	Laude I , Rongières-Bertrand C , Boyer-Neumann C , et al. Circulating procoagulant microparticles in women with unexplained pregnancy loss: A new insight[J]. Thromb Haemost, 2001, 85 (1): 18- 21. doi: 10.1055/s-0037-1612657
19	Ushida T , Kotani T , Moriyama Y , et al. Platelet counts during normal pregnancies and pregnancies complicated with hypertensive disorders[J]. Pregnancy Hypertens, 2021, 24 (2): 73- 78.
20	Subtil S FC , Mendes JMB , Areia ALFD , et al. Update on thrombocytopenia in pregnancy[J]. Rev Bras Ginecol Obstet, 2020, 42 (12): 834- 840. doi: 10.1055/s-0040-1721350
21	Reese JA , Peck JD , Deschamps DR , et al. Platelet counts during pregnancy[J]. N Engl J Med, 2018, 379 (1): 32- 43. doi: 10.1056/NEJMoa1802897
22	Liu J , Zhao Y , Song Y , et al. Pregnancy in women with systemic lupus erythematosus: A retrospective study of 111 pregnancies in Chinese women[J]. J Matern Fetal Neonatal Med, 2012, 25 (3): 261- 266. doi: 10.3109/14767058.2011.572310
23	Nalli C , Lini D , Andreoli L , et al. Low preconception complement levels are associated with adverse pregnancy outcomes in a multicenter study of 260 pregnancies in 197 women with antiphospholipid syndrome or carriers of antiphospholipid antibodies[J]. Biomedicines, 2021, 9 (6): 671.
24	Girardi G , Yarilin D , Thurman J M , et al. Complement activation induces dysregulation of angiogenic factors and causes fetal rejection and growth restriction[J]. J Exp Med, 2006, 203 (9): 2165- 2175.
25	Buyon JP , Kim MY , Guerra MM , et al. Predictors of pregnancy outcomes in patients with lupus[J]. Ann Intern Med, 2015, 163 (3): 153- 163.
26	Smyth A , Oliveira GHM , Lahr BD , et al. A systematic review and meta-analysis of pregnancy outcomes in patients with systemic lupus erythematosus and lupus nephritis[J]. Clin J Am Soc Nephrol, 2010, 5 (11): 2060- 2068.
27	Hladunewich MA . Chronic kidney disease and pregnancy[J]. Semin Nephrol, 2017, 37 (4): 337- 346.
28	Stern C , Chamley L . Antiphospholipid antibodies and coagulation defects in women with implantation failure after IVF and recurrent miscarriage[J]. Reprod BioMed Online, 2006, 13 (1): 29- 37.
29	Saccone G , Berghella V , Maruotti GM , et al. Antiphospholipid antibody profile based obstetric outcomes of primary antiphospholipid syndrome: The PREGNANTS study[J]. Am J Obstet Gynecol, 2017, 216 (5): 525.el- 525.e12.
30	de Carolis S , Tabacco S , Rizzo F , et al. Antiphospholipid syndrome: An update on risk factors for pregnancy outcome[J]. Autoimmun Rev, 2018, 17 (10): 956- 966.
31	Andreoli L , Bertsias GK , Agmon-Levin N , et al. EULAR recommendations for women' s health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome[J]. Ann Rheum Dis, 2017, 76 (3): 476- 485.

相关文章 15

[1]	杨树涵, 李奕昕, 崔浩亮, 王佑新, 吴玉莹, 王明月, 杨依凡, 恩卡尔·努尔, 杨磊, 王辉. 代谢相关脂肪性肝病及其心脏代谢风险指标异常与不良妊娠结局的相关性[J]. 北京大学学报（医学版）, 2025, 57(3): 487-495.
[2]	王红彦, 李鑫铭, 房柯池, 朱华群, 贾汝琳, 王晶. 系统性红斑狼疮疾病活动度相关特征分析及评估模型的构建[J]. 北京大学学报（医学版）, 2024, 56(6): 1017-1022.
[3]	陈丹丹, 李云, 卢情怡, 相晓红, 孙峰, 李英妮, 赵静, 王红彦, 李春. 育龄期系统性红斑狼疮患者卵巢功能的评价及其影响因素[J]. 北京大学学报（医学版）, 2024, 56(6): 1023-1028.
[4]	王莉, 高超, 任欢欢, 沈艳平, 黄晓玮, 姚鸿, 韩丹丹. 系统性红斑狼疮患者自我管理能力现状及相关因素分析[J]. 北京大学学报（医学版）, 2024, 56(6): 1029-1035.
[5]	柴静, 王钥, 穆荣, 赵金霞. 系统性红斑狼疮累及穹窿柱导致低钠血症1例[J]. 北京大学学报（医学版）, 2024, 56(6): 1115-1118.
[6]	王明霞, 丁菱, 王敏, 邹婵娟, 颜丝语, 梁颖文, 王伟佳, 何善智. 双靶点嵌合抗原受体T细胞治疗系统性红斑狼疮患者停药后安全孕产1例[J]. 北京大学学报（医学版）, 2024, 56(6): 1119-1125.
[7]	武志慧, 胡明智, 赵巧英, 吕凤凤, 张晶莹, 张伟, 王永福, 孙晓林, 王慧. miR-125b-5p修饰脐带间充质干细胞对系统性红斑狼疮的免疫调控机制[J]. 北京大学学报（医学版）, 2024, 56(5): 860-867.
[8]	乔佳佳,田聪,黄晓波,刘军. 肾结石合并系统性红斑狼疮行经皮肾镜碎石取石术的安全性和有效性评估[J]. 北京大学学报（医学版）, 2024, 56(4): 745-749.
[9]	任立敏,赵楚楚,赵义,周惠琼,张莉芸,王友莲,沈凌汛,范文强,李洋,厉小梅,王吉波,程永静,彭嘉婧,赵晓珍,邵苗,李茹. 系统性红斑狼疮低疾病活动度及缓解状况的真实世界研究[J]. 北京大学学报（医学版）, 2024, 56(2): 273-278.
[10]	赵祥格,刘佳庆,黄会娜,陆智敏,白自然,李霞,祁荆荆. 干扰素-α介导系统性红斑狼疮外周血CD56^dimCD57⁺自然杀伤细胞功能的损伤[J]. 北京大学学报（医学版）, 2023, 55(6): 975-981.
[11]	姚海红,杨帆,唐素玫,张霞,何菁,贾园. 系统性红斑狼疮及成人Still病合并巨噬细胞活化综合征的临床特点及诊断指标[J]. 北京大学学报（医学版）, 2023, 55(6): 966-974.
[12]	罗芷筠,吴佳佳,宋优,梅春丽,杜戎. 伴神经精神系统病变的系统性红斑狼疮相关巨噬细胞活化综合征2例[J]. 北京大学学报（医学版）, 2023, 55(6): 1111-1117.
[13]	游芳凝,罗靓,刘香君,张学武,李春. 未分化结缔组织病患者的妊娠结局、疾病演变及其影响因素[J]. 北京大学学报（医学版）, 2023, 55(6): 1045-1052.
[14]	邵苗,郭惠芳,雷玲彦,赵清,丁艳杰,林进,吴锐,于峰,李玉翠,苗华丽,张莉芸,杜燕,焦瑞英,庞丽霞,龙丽,栗占国,李茹. 短间期小剂量环磷酰胺治疗系统性红斑狼疮耐受性的多中心对照研究[J]. 北京大学学报（医学版）, 2022, 54(6): 1112-1116.
[15]	李敏,侯林卿,金月波,何菁. 系统性红斑狼疮合并视网膜病变的临床及免疫学特点[J]. 北京大学学报（医学版）, 2022, 54(6): 1106-1111.

Metrics

Viewed

Full text

Abstract

Cited

Shared

Discussed

Items	APOs group (n=85)	Non-APOs group (n=233)	t/χ²	P
Age at diagnosis of SLE/years, $\bar x \pm s$	24.20±5.36	24.96±5.20	1.262	0.208
Disease duration/years, $\bar x \pm s$	8.59±6.00	7.35±4.56	1.028	0.307
Clinical manifestations
Malar rash, n (%)	23 (27.06)	60 (25.75)	0.055	0.814
Photosensitivity, n (%)	8 (9.41)	18 (7.73)	0.236	0.627
Oral ulcers, n (%)	5 (5.88)	7 (3.00)	1.421	0.233
Fever, n (%)	24 (28.24)	61 (26.18)	0.134	0.714
Arthritis, n (%)	21 (24.71)	54 (23.18)	0.081	0.776
Myositis, n (%)	2 (2.35)	8 (3.43)	0.239	0.625
Serositis, n (%)	4 (4.71)	11 (4.72)	0	>0.999
Vasculitis, n (%)	2 (2.35)	1 (0.43)	2.466	0.116
LN, n (%)	27 (31.76)	49 (21.03)	3.946	0.047^*
NPSLE, n (%)	3 (3.53)	7 (3.00)	0.056	0.812
Haematologic disorder, n (%)	46 (54.12)	92 (39.48)	5.429	0.020^*
Laboratory indexes
Leukopenia, n (%)	10 (11.76)	34 (14.59)	0.418	0.518
Anemia, n (%)	30 (35.29)	62 (26.61)	2.285	0.131
Thrombocytopenia, n (%)	21 (24.71)	21 (9.01)	13.38	< 0.001^*
Hypocomplementemia, n (%)	31 (36.47)	56 (26.03)	4.847	0.028^*
Anti-dsDNA positivity, n (%)	20 (23.53)	42 (18.03)	1.202	0.273
Antiphospholipid antibodies positivity, n (%)	17 (20.00)	26 (11.16)	4.163	0.041^*
SLEDAI-2000, $\bar x \pm s$	5.82±4.97	3.74±3.72	4.019	0.001^*