Department of Internal Medicine Division of Pharmacology and Vascular Medicine Erasmus Medical Center Rotterdam The Netherlands.
Department of Gynecology and Obstetrics Erasmus Medical Center Rotterdam Rotterdam The Netherlands.
J Am Heart Assoc. 2020 Oct 20;9(19):e018219. doi: 10.1161/JAHA.120.018219. Epub 2020 Sep 29.
Background We aimed to evaluate the value of inhibin A and PAPP-A2 (pregnancy-associated plasma protein-A2) as novel biomarkers in the prediction of preeclampsia-related complications and how they compare with angiogenic biomarkers. Methods and Results Making use of a secondary analysis of a prospective, multicenter, observational study, intended to evaluate the usefulness of sFlt-1 (soluble Fms-like tyrosine kinase-1)/PlGF (placental growth factor) ratio, we measured inhibin A and PAPP-A2 levels in 524 women with suspected/confirmed preeclampsia. Women had a median gestational age of 35 weeks (range, 20-41 weeks) while preeclampsia occurred in 170 (32%) women. Levels of inhibin A and PAPP-A2 were significantly increased in women with preeclampsia and in maternal perfusate of preeclamptic placentas. Inhibin A and PAPP-A2 (C-index = 0.73 and 0.75) significantly improved the prediction of maternal complications when added on top of the traditional criteria; gestational age, parity, proteinuria, and diastolic blood pressure (C-index = 0.60). PAPP-A2 was able to improve the C-index from 0.75 to 0.77 when added on top of the sFlt-1/PlGF ratio for the prediction of maternal complications. To discriminate fetal/neonatal complications on top of traditional criteria, inhibin A and PAPP-A2 showed additive value (C-index = 0.79 to 0.80 and 0.82, respectively) but their discriminative ability remained inferior to that of sFlt-1/PlGF ratio or PlGF. Interestingly, the PAPP-A2/PlGF ratio alone showed remarkable value to predict pregnancy complications, being superior to sFlt-1/PlGF ratio in the case of maternal complications. Conclusions Inhibin A and PAPP-A2 show significant potential to predict preeclampsia-related pregnancy complications and might prove beneficial on top of the angiogenic markers.
背景 我们旨在评估抑制素 A 和 PAPP-A2(妊娠相关血浆蛋白-A2)作为预测子痫前期相关并发症的新型生物标志物的价值,以及它们与血管生成生物标志物的比较。
方法和结果 利用一项旨在评估可溶性 Fms 样酪氨酸激酶-1(sFlt-1)/胎盘生长因子(PlGF)比值有用性的前瞻性、多中心、观察性研究的二次分析,我们测量了 524 例疑似/确诊子痫前期妇女的抑制素 A 和 PAPP-A2 水平。这些妇女的中位孕周为 35 周(范围为 20-41 周),其中 170 例(32%)患有子痫前期。子痫前期妇女和子痫前期胎盘母体灌流液中抑制素 A 和 PAPP-A2 水平显著升高。抑制素 A 和 PAPP-A2(C 指数分别为 0.73 和 0.75)在传统标准的基础上显著改善了对母体并发症的预测;C 指数为 0.60)。当添加到 sFlt-1/PlGF 比值之上时,PAPP-A2 能够将预测母体并发症的 C 指数从 0.75 提高到 0.77。为了在传统标准的基础上区分胎儿/新生儿并发症,抑制素 A 和 PAPP-A2 显示出附加价值(C 指数分别为 0.79 至 0.80 和 0.82),但它们的区分能力仍低于 sFlt-1/PlGF 比值或 PlGF。有趣的是,单独的 PAPP-A2/PlGF 比值显示出显著预测妊娠并发症的价值,在母体并发症方面优于 sFlt-1/PlGF 比值。
结论 抑制素 A 和 PAPP-A2 具有显著预测子痫前期相关妊娠并发症的潜力,并且可能在血管生成标志物的基础上受益。