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系统性红斑狼疮患者妊娠的风险分层与亚组分析:基于一项13年的多中心队列研究

Risk stratification and subgroup analysis of systemic lupus erythematosus patients with pregnancy: based on a 13-year multicenter cohort study.

作者信息

Liu Lingshan, Huang Can, Li Hongbin, Duan Xinwang, Wu Zhenbiao, Zhan Feng, Shu Qiang, Wei Wei, Tong Shengquan, Wang Qian, Song Yijun, Li Mengtao, Zeng Xiaofeng, Tian Xinping, Zhao Jiuliang

机构信息

Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, State Key Laboratory of Complex Severe and Rare Diseases, Key Laboratory of Rheumatology and Clinical Immunology, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Chinese Academy of Medical Science and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Ave, Beijing, 100730, China.

Department of Rheumatology, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, China.

出版信息

Clin Rheumatol. 2025 Aug 12. doi: 10.1007/s10067-025-07552-3.

Abstract

OBJECTIVES

Systemic lupus erythematosus (SLE) presents with heterogeneous clinical manifestations and pregnancy outcomes, complicating its pregnancy management. This study aimed to identify distinct subgroups of pregnant SLE patients and explore their prognostic implications.

METHOD

In this multicenter cohort study across 45 centers in China, 25 baseline variables were incorporated into a cluster analysis (CA) considering collinearity and clinical relevance. Pregnancy outcomes were compared across clusters, and logistic regressions were conducted for total adverse pregnancy outcome (APO) in the overall cohort and each cluster.

RESULTS

Among 528 pregnancies in 499 patients, 72.7% were planned and 35.4% had positive antiphospholipid antibody (aPL). Living birth rate was 81.1%, and 41.5% experienced ≥ 1 APO. Four clusters were defined. Cluster 1 (n = 176), characterized by serological activity, had slightly higher fetal loss (20.5%). Cluster 2 (n = 117), with high aCL/aβ2GPI positivity but low LA, high planned pregnancy rate (91.5%), and more HCQ and aspirin use, had favorable outcomes. Cluster 3 (n = 194), with high planned pregnancy rate (85.1%) and lowest aPL positivity (28.4%), exhibited the best outcomes. Cluster 4 (n = 41), with lowest planned pregnancy (9.8%), most clinical activity, and highest aPL positivity (70.7%) including LA (53.7%), exhibited most APOs (75.6%), with hypocomplementemia further increasing risk (OR = 9.246, p = 0.022).

CONCLUSIONS

Four clinically meaningful SLE-pregnancy subgroups were identified, each with distinct APO risk. Our findings underscore the harm of unplanned pregnancy, especially clinical activity, and aPL positivity, particularly LA, thus promoted stratification and personalized management in SLE pregnancy. Key points • Four distinct subtypes of pregnant SLE patients were identified, each with different APO risks and predictors. • Major organ activity and LA positivity were strongly associated with higher APO risk, while isolated serological activity and non-LA aPL positivity conferred only modest risk. • HCQ appeared protective, especially in aPL-positive patients, whereas medium to high dose glucocorticoid may be harmful, particularly in those with stable disease. • These findings highlight the importance of early risk stratification and individualized management in SLE pregnancy.

摘要

目的

系统性红斑狼疮(SLE)临床表现多样,妊娠结局各异,使其妊娠管理变得复杂。本研究旨在识别妊娠SLE患者的不同亚组,并探讨其预后意义。

方法

在这项涵盖中国45个中心的多中心队列研究中,考虑到共线性和临床相关性,将25个基线变量纳入聚类分析(CA)。比较各聚类间的妊娠结局,并对整个队列及每个聚类的总不良妊娠结局(APO)进行逻辑回归分析。

结果

499例患者的528次妊娠中,72.7%为计划妊娠,35.4%抗磷脂抗体(aPL)阳性。活产率为81.1%,41.5%经历了≥1次APO。定义了四个聚类。聚类1(n = 176),以血清学活动为特征,胎儿丢失率略高(20.5%)。聚类2(n = 117),aCL/aβ2GPI阳性率高但狼疮抗凝物(LA)低,计划妊娠率高(91.5%),使用羟氯喹(HCQ)和阿司匹林更多,结局良好。聚类3(n = 194),计划妊娠率高(85.1%)且aPL阳性率最低(28.4%),表现出最佳结局。聚类4(n = 41),计划妊娠率最低(9.8%),临床活动最多,aPL阳性率最高(70.7%)包括LA(53.7%),表现出最多的APO(75.6%),低补体血症进一步增加风险(OR = 9.246,p = 0.022)。

结论

识别出四个具有临床意义的SLE妊娠亚组,每个亚组具有不同的APO风险。我们的研究结果强调了意外妊娠的危害,尤其是临床活动和aPL阳性,特别是LA,从而促进了SLE妊娠的分层和个性化管理。要点 • 识别出妊娠SLE患者的四种不同亚型,各亚型具有不同的APO风险和预测因素。 • 主要器官活动和LA阳性与较高的APO风险密切相关,而单纯血清学活动和非LA aPL阳性仅带来适度风险。 • HCQ似乎具有保护作用,尤其是在aPL阳性患者中,而中高剂量糖皮质激素可能有害,特别是在病情稳定的患者中。 • 这些发现突出了SLE妊娠早期风险分层和个体化管理的重要性。

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