The First Clinical College of Chongqing Medical University, Chongqing, China.
Department of Obstetrics, Chengdu Jinjiang Maternity and Child Health Hospital, Chengdu, China.
Lupus. 2021 Jan;30(1):70-79. doi: 10.1177/0961203320967097. Epub 2020 Oct 20.
To compare and rank currently available pharmacological interventions for the prevention of recurrent miscarriage (RM) in women with antiphospholipid syndrome (APS).
A search was performed using PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, CNKI, ClinicalTrials.gov, and the UK National Research Register on December 15, 2019. Studies comparing any types of active interventions with placebo/inactive control or another active intervention for the prevention of RM in patients with APS were considered for inclusion. The primary outcomes were efficacy (measured by live birth rate) and acceptability (measured by all-cause discontinuation); secondary outcomes were birthweight, preterm birth, preeclampsia, and intrauterine growth retardation. The protocol of this study was registered with Open Science Framework (DOI: 10.17605/OSF.IO/B9T4E).
In total, 54 randomized controlled trials (RCTs) comprising 4,957 participants were included. Low-molecular-weight heparin (LMWH) alone, aspirin plus LMWH or unfractionated heparin (UFH), aspirin plus LMWH plus intravenous immunoglobulin (IVIG), aspirin plus LMWH plus IVIG plus prednisone were found to be effective pharmacological interventions for increasing live birth rate (ORs ranging between 2.88 to 11.24). In terms of acceptability, no significant difference was found between treatments. In terms of adverse perinatal outcomes, aspirin alone was associated with a higher risk of preterm birth than aspirin plus LMWH (OR 3.92, 95% CI 1.16 to 16.44) and with lower birthweight than LMWH (SMD -808.76, 95% CI -1596.54 to -5.07).
Our findings support the use of low-dose aspirin plus heparin as the first-line treatment for prevention of RM in women with APS, and support the efficacy of hydroxychloroquine, IVIG, and prednisone when added to current treatment regimens. More large-scale, high-quality RCTs are needed to confirm these findings, and new pharmacological options should be further evaluated.
比较和评估目前可用于预防抗磷脂综合征（APS）女性复发性流产（RM）的药物干预措施。
于 2019 年 12 月 15 日在 PubMed、Embase、Cochrane 对照试验中心注册库、Web of Science、中国知网（CNKI）、ClinicalTrials.gov 和英国国家研究注册中心进行检索，纳入比较任何类型的活性干预措施与安慰剂/非活性对照或另一种活性干预措施预防 APS 患者 RM 的研究。主要结局指标为有效性（以活产率衡量）和可接受性（以全因停药率衡量）；次要结局指标为出生体重、早产、子痫前期和宫内生长迟缓。本研究方案已在开放科学框架（DOI：10.17605/OSF.IO/B9T4E）上注册。
共纳入 54 项随机对照试验（RCTs），共计 4957 名参与者。低分子肝素（LMWH）单药、阿司匹林加 LMWH 或未分级肝素（UFH）、阿司匹林加 LMWH 加静脉注射免疫球蛋白（IVIG）、阿司匹林加 LMWH 加 IVIG 加泼尼松均被认为是增加活产率的有效药物干预措施（比值比范围为 2.88 至 11.24）。在可接受性方面，各治疗组之间无显著差异。在围产期不良结局方面，与阿司匹林加 LMWH 相比，阿司匹林单药治疗早产风险更高（比值比 3.92，95%置信区间 1.16 至 16.44），且出生体重更低（标准化均数差 -808.76，95%置信区间-1596.54 至-5.07）。
本研究结果支持低剂量阿司匹林加肝素作为 APS 女性 RM 预防的一线治疗，同时也支持羟氯喹、IVIG 和泼尼松在现有治疗方案中的疗效。需要更多大规模、高质量的 RCT 来证实这些发现，并进一步评估新的药物治疗选择。
