Objective Studies in mouse models implicate complement activation as a causative factor in adverse pregnancy outcomes (APOs). We investigated whether activation of complement early in pregnancy predicts APOs in women with systemic lupus erythematosus (SLE) and/or antiphospholipid (aPL) antibodies. Methods The PROMISSE Study enrolled pregnant women with SLE and/or aPL antibodies (n=487) and pregnant healthy controls (n=204) at <12 weeks gestation and evaluated them monthly. APOs were: fetal/neonatal death, preterm delivery <36 weeks because of placental insufficiency or preeclampsia and/or growth restriction <5th percentile. Complement activation products were measured on serial blood samples obtained at each monthly visit. Results APO occurred in 20.5% of SLE and/or aPL pregnancies. As early as 12–15 weeks, levels of Bb and sC5b-9 were significantly higher in patients with APOs and remained elevated through 31 weeks compared with those with normal outcomes. Moreover, Bb and sC5b-9 were significantly higher in patients with SLE and/or aPL without APOs compared with healthy controls. In logistic regression analyses, Bb and sC5b-9 at 12–15 weeks remained significantly associated with APO (ORadj=1.41 per SD increase; 95% CI 1.06 to 1.89; P=0.019 and ORadj=1.37 per SD increase; 95% CI 1.05 to 1.80; P=0.022, respectively) after controlling for demographic and clinical risk factors for APOs in PROMISSE. When analyses were restricted to patients with aPL (n=161), associations between Bb at 12–15 weeks and APOs became stronger (ORadj=2.01 per SD increase; 95% CI 1.16 to 3.49; P=0.013). Conclusion In pregnant patients with SLE and/or aPL, increased Bb and sC5b-9 detectable early in pregnancy are strongly predictive of APOs and support activation of complement, particularly the alternative pathway, as a contributor to APOs.

中文翻译：

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补体激活可预测系统性红斑狼疮和/或抗磷脂抗体患者的不良妊娠结局

小鼠模型中的目标研究表明补体激活是不良妊娠结局 (APO) 的一个致病因素。我们调查了妊娠早期补体的激活是否可以预测患有系统性红斑狼疮 (SLE) 和/或抗磷脂 (aPL) 抗体的女性的 APO。方法 PROMISSE 研究招募了具有 SLE 和/或 aPL 抗体的孕妇 (n=487) 和怀孕健康对照 (n=204) 在 <12 周妊娠并每月对其进行评估。APOs 是：胎儿/新生儿死亡，由于胎盘功能不全或先兆子痫和/或生长受限<第 5 个百分位导致的早产 <36 周。补体激活产物在每个月访问时获得的系列血样上进行测量。结果 APO 发生在 20.5% 的 SLE 和/或 aPL 妊娠中。早在 12-15 周，与结果正常的患者相比，APO 患者的 Bb 和 sC5b-9 水平显着更高，并且在 31 周内保持升高。此外，与健康对照相比，没有 APO 的 SLE 和/或 aPL 患者的 Bb 和 sC5b-9 显着更高。在逻辑回归分析中，12-15 周时的 Bb 和 sC5b-9 仍然与 APO 显着相关（ORadj=1.41/SD 增加；95% CI 1.06 至 1.89；P=0.019 和 ORadj=1.37/SD 增加；95% CI 1.05到 1.80；分别为 P=0.022）在控制 PROMISSE 中 APO 的人口统计学和临床​​危险因素后。当分析仅限于 aPL 患者（n=161）时，12-15 周时的 Bb 与 APO 之间的关联变得更强（ORadj=2.01/SD 增加；95% CI 1.16 至 3.49；P=0.013）。结论 在妊娠期 SLE 和/或 aPL 患者中，