Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe, Japan.
Department of Obstetrics and Gynecology, University of Toyama, Toyama, Japan.
Front Immunol. 2024 Sep 26;15:1445852. doi: 10.3389/fimmu.2024.1445852. eCollection 2024.
Anti-β2-glycoprotein I (β2GPI)/human leukocyte antigen (HLA)-DR antibodies may be a risk factor for recurrent pregnancy loss (RPL). The therapeutic modality for women with RPL and anti-β2GPI/HLA-DR antibody positivity has not been evaluated. This prospective, multicenter, observational study aimed to assess whether low-dose aspirin (LDA) and/or heparin therapies improve pregnancy outcomes in women with RPL who tested positive for anti-β2GPI/HLA-DR antibodies.
Between August 2019 and December 2021, 462 women with RPL underwent anti-β2GPI/HLA-DR antibody measurements and risk assessments for RPL. Each attending physician decided the treatment modality for women with RPL who tested positive for anti-β2GPI/HLA-DR antibodies, and their pregnancy outcomes were followed up until December 2023. Finally, 47 pregnancies in 47 women with RPL and anti-β2GPI/HLA-DR antibody positivity were included in the analysis and were divided into two groups regarding whether they were treated with LDA and/or unfractionated heparin (UFH) (LDA/UFH group, n = 39) or with neither of them (non-LDA/non-UFH group, n = 8). The rates of live birth and pregnancy complications (i.e., preeclampsia and preterm delivery before 34 gestational weeks due to placental insufficiency) were compared between the two groups.
The live birth rate in the LDA/UFH group was higher than that in the non-LDA/non-UFH group (87.2% vs 50.0%, = 0.03). The pregnancy complication rate in the LDA/UFH group was significantly lower than that in the non-LDA/non-UFH group (5.9% vs 50.0%, = 0.048). Among 21 women who tested positive for anti-β2GPI/HLA-DR antibodies and had no other risk factors for RPL, the live birth rate in the LDA/UFH group (n = 14) was much higher than that in the non-LDA/non-UFH group (n = 7) (92.9% vs 42.9%, = 0.03).
This study, for the first time, demonstrated that LDA and/or UFH therapies are effective in improving pregnancy outcomes in women with RPL and aβ2GPI/HLA-DR antibody positivity.
抗β2-糖蛋白 I（β2GPI）/人类白细胞抗原（HLA）-DR 抗体可能是复发性妊娠丢失（RPL）的一个危险因素。尚未评估 RPL 伴抗β2GPI/HLA-DR 抗体阳性妇女的治疗方式。本前瞻性、多中心、观察性研究旨在评估低剂量阿司匹林（LDA）和/或肝素治疗是否能改善抗β2GPI/HLA-DR 抗体阳性的 RPL 妇女的妊娠结局。
2019 年 8 月至 2021 年 12 月，462 名 RPL 妇女进行了抗β2GPI/HLA-DR 抗体检测和 RPL 风险评估。每位主治医生决定了抗β2GPI/HLA-DR 抗体阳性的 RPL 妇女的治疗方式，并随访其妊娠结局至 2023 年 12 月。最终，47 名 RPL 伴抗β2GPI/HLA-DR 抗体阳性的妇女（n = 47）纳入分析，并根据是否接受 LDA 和/或未分级肝素（UFH）治疗（LDA/UFH 组，n = 39）或未接受任何治疗（非 LDA/非 UFH 组，n = 8）分为两组。比较两组的活产率和妊娠并发症（即由于胎盘功能不全导致的子痫前期和 34 孕周前早产）。
LDA/UFH 组的活产率高于非 LDA/非 UFH 组（87.2% vs 50.0%，= 0.03）。LDA/UFH 组的妊娠并发症发生率明显低于非 LDA/非 UFH 组（5.9% vs 50.0%，= 0.048）。在 21 名抗β2GPI/HLA-DR 抗体阳性且无其他 RPL 危险因素的妇女中，LDA/UFH 组（n = 14）的活产率明显高于非 LDA/非 UFH 组（n = 7）（92.9% vs 42.9%，= 0.03）。
本研究首次表明，LDA 和/或 UFH 治疗可有效改善抗β2GPI/HLA-DR 抗体阳性的 RPL 妇女的妊娠结局。
