Chirilă Cristian Nicolae, Mărginean Claudiu, Chirilă Paula Maria, Gliga Mirela Liana
Department of Internal Medicine-Nephrology, Doctoral School, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, 540142 Târgu Mureș, Romania.
Department of Nephrology, Mures Clinical County Hospital, 540103 Târgu Mureș, Romania.
Children (Basel). 2023 Aug 22;10(9):1430. doi: 10.3390/children10091430.
Regarding the hypertensive disorders of pregnancy, pre-eclampsia (PE) remains one of the leading causes of severe and life-threatening maternal and fetal complications. Screening of early-onset PE (<34 weeks of pregnancy), as well as late-onset PE (≥34 weeks), shows poor performance if based solely on clinical features. In recent years, biochemical markers from maternal blood-the pro-angiogenic protein placental growth factor (PlGF) and the antiangiogenic protein soluble FMS-like tyrosine kinase 1 (sFlt-1)-and Doppler velocimetry indices-primarily the mean uterine pulsatility index (PI), but also the uterine resistivity index (RI), the uterine systolic/diastolic ratio (S/D), uterine and umbilical peak systolic velocity (PSV), end-diastolic velocity (EDV), and uterine notching-have all shown improved screening performance. In this review, we summarize the current status of knowledge regarding the role of biochemical markers and Doppler velocimetry indices in early prediction of the onset and severity of PE and other placenta-related disorders, as well as their role in monitoring established PE and facilitating improved obstetrical surveillance of patients categorized as high-risk in order to prevent adverse outcomes. A sFlt-1/PlGF ratio ≤ 33 ruled out early-onset PE with 95% sensitivity and 94% specificity, whereas a sFlt-1/PlGF ≥88 predicted early-onset PE with 88.0% sensitivity and 99.5% specificity. Concerning the condition's late-onset form, sFlt-1/PlGF ≤ 33 displayed 89.6% sensitivity and 73.1% specificity in ruling out the condition, whereas sFlt-1/PlGF ≥ 110 predicted the condition with 58.2% sensitivity and 95.5% specificity. The cut-off values of the sFlt-1/PlGF ratio for the screening of PE were established in the PROGNOSIS study: a sFlt-1/PlGF ratio equal to or lower than 38 ruled out the onset of PE within one week, regardless of the pregnancy's gestational age. The negative predictive value in this study was 99.3%. In addition, sFlt-1/PlGF > 38 showed 66.2% sensitivity and 83.1% specificity in predicting the occurrence of PE within 4 weeks. Furthermore, 2018 ISUOG Practice Guidelines stated that a second-trimester mean uterine artery PI ≥ 1.44 increases the risk of later PE development. The implementation of a standard screening procedure based on the sFlt-1/PlGF ratio and uterine Doppler velocimetry may improve early detection of pre-eclampsia and other placenta-related disorders.
关于妊娠高血压疾病，子痫前期（PE）仍然是导致严重且危及生命的母婴并发症的主要原因之一。仅基于临床特征对早发型PE（妊娠<34周）以及晚发型PE（≥34周）进行筛查，效果不佳。近年来，来自母体血液的生化标志物——促血管生成蛋白胎盘生长因子（PlGF）和抗血管生成蛋白可溶性FMS样酪氨酸激酶1（sFlt-1）——以及多普勒测速指数——主要是子宫平均搏动指数（PI），还有子宫阻力指数（RI）、子宫收缩期/舒张期比值（S/D）、子宫和脐动脉收缩期峰值流速（PSV）、舒张末期流速（EDV）以及子宫切迹——均显示出筛查性能有所改善。在本综述中，我们总结了目前关于生化标志物和多普勒测速指数在早期预测PE及其他胎盘相关疾病的发病和严重程度方面的作用的知识现状，以及它们在监测已确诊的PE和促进对高危患者进行更好的产科监测以预防不良结局方面的作用。sFlt-1/PlGF比值≤33排除早发型PE的敏感度为95%，特异度为94%，而sFlt-1/PlGF≥88预测早发型PE的敏感度为88.0%，特异度为99.5%。对于该疾病的晚发型形式，sFlt-1/PlGF≤33排除该疾病的敏感度为89.6%，特异度为73.1%，而sFlt-1/PlGF≥110预测该疾病的敏感度为58.2%，特异度为95.5%。PROGNOSIS研究确定了用于筛查PE的sFlt-1/PlGF比值的临界值：sFlt-1/PlGF比值等于或低于38可排除一周内PE的发病，无论妊娠孕周如何。该研究中的阴性预测值为99.3%。此外，sFlt-1/PlGF>38在预测4周内PE发生方面的敏感度为66.2%，特异度为83.1%。此外，2018年国际妇产科超声学会（ISUOG）实践指南指出，孕中期子宫动脉平均PI≥1.44会增加后期发生PE的风险。基于sFlt-1/PlGF比值和子宫多普勒测速实施标准筛查程序可能会改善子痫前期和其他胎盘相关疾病的早期检测。
