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sFlt-1/PLGF比值≥110在临床疑似晚发型子痫前期孕妇中的辅助诊断与风险评估价值：一项单中心队列研究
狄小丹, 潘秀玉, 钟俊敏, 陈运山, 赵繁星, 蒋艳敏, 胡敏华, 刘慧姝
中国实用妇科与产科杂志 ›› 2026, Vol. 42 ›› Issue (7) : 740-744.
PDF(1071 KB)
PDF(1071 KB)
sFlt-1/PLGF比值≥110在临床疑似晚发型子痫前期孕妇中的辅助诊断与风险评估价值：一项单中心队列研究
Application of the sFlt-1/PLGF ratio ≥110 for auxiliary diagnosis and risk assessment in pregnant women with clinically suspected late-onset preeclampsia：a single-center cohort study
目的 在临床疑似但尚未确诊晚发型子痫前期（LOP）的孕晚期单胎孕妇中，探讨可溶性酪氨酸激酶-1（sFlt-1）/胎盘生长因子（PLGF）比值≥110作为辅助诊断与病情评估工具的价值。方法 纳入广州医科大学附属妇女儿童医疗中心2021年1月至2023年12月期间孕周≥34周、疑似LOP的单胎孕妇632例。采集疑似症状出现后24 h内的血样，检测sFlt-1与PLGF水平并计算比值。根据比值是否≥110分组，比较两组子痫前期发生率、严重程度及母儿结局。结果 最终诊断为LOP者245例（38.77%）。以sFlt-1/PLGF比值≥110为阈值，诊断LOP的阳性预测值（PPV）为87.50%，阴性预测值（NPV）为71.73%，特异度为96.38%，灵敏度为40.00%，受试者工作特征（ROC）曲线下面积（AUC）为0.824。比值≥110组重度子痫前期发生率、胎儿生长受限（FGR）及新生儿重症监护病房（NICU）入住率均显著高于比值<110组（P<0.01）。在确诊LOP的亚组分析中，比值≥110者病情更重，不良结局风险更高。结论 sFlt-1/PLGF比值≥110对中国人群疑似LOP具有较高的特异性及阳性预测价值，可有效识别病情严重、母儿结局不良的高危孕妇，适用于临床辅助诊断与风险评估。
Objective To evaluate the value of the sFlt-1/PLGF ratio ≥110 as an adjunct diagnostic and disease assessment tool in singleton pregnant women in late gestation with clinically suspected but not yet confirmed late-onset preeclampsia （LOP）. Methods A total of 632 singleton pregnant women with gestational age ≥34 weeks and suspected late-onset preeclampsia （LOP）in Guangzhou Women and Children's Medical Center between January 2021 and December 2023 were enrolled. Blood samples were collected within 24 hours after the onset of suspected symptoms，and sFlt-1 and PLGF levels were measured to calculate their ratio. Patients were divided into two groups based on whether the ratio was ≥110，and the incidence and severity of preeclampsia，and maternal and fetal outcomes were compared between the two groups. Results A total of 245 cases （38.77%） were ultimately diagnosed with LOP. Using a threshold of sFlt-1/PLGF ratio ≥110 for diagnosing LOP，the positive predictive value （PPV） was 87.50%，negative predictive value （NPV） was 71.73%，specificity was 96.38%，sensitivity was 40.00%，and the area under the ROC curve （AUC） was 0.824. The incidence of severe preeclampsia，fetal growth restriction （FGR），and neonatal intensive care unit （NICU） admission was significantly higher in the group with a ratio ≥110 compared to the group with a ratio<110 （P<0.01）. In subgroup analysis of confirmed LOP cases，those with a ratio ≥110 had more severe disease and a higher risk of adverse outcomes. Conclusion An sFlt-1/PLGF ratio ≥110 has high specificity and positive predictive value for suspected LOP in Chinese populations，which can effectively identify high-risk pregnant women with severe disease and poor maternal-fetal outcomes，making it suitable for clinical auxiliary diagnosis and risk assessment.
sFlt-1/PlGF比值 / 晚发型子痫前期 / 诊断 / 病情评估 / 不良结局
sFlt-1/PLGF ratio / late-onset preeclampsia / diagnosis / disease severity assessment / adverse outcomes
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ACOG. Gestational Hypertension and Preeclampsia:ACOG Practice Bulletin,Number 222[J]. Obstet Gynecol, 2020, 135(6):e237-e260. DOI:10.1097/AOG.0000000000003891.
Hypertensive disorders of pregnancy constitute one of the leading causes of maternal and perinatal mortality worldwide. It has been estimated that preeclampsia complicates 2–8% of pregnancies globally (1). In Latin America and the Caribbean, hypertensive disorders are responsible for almost 26% of maternal deaths, whereas in Africa and Asia they contribute to 9% of deaths. Although maternal mortality is much lower in high-income countries than in developing countries, 16% of maternal deaths can be attributed to hypertensive disorders (1, 2). In the United States, the rate of preeclampsia increased by 25% between 1987 and 2004 (3). Moreover, in comparison with women giving birth in 1980, those giving birth in 2003 were at 6.7-fold increased risk of severe preeclampsia (4). This complication is costly: one study reported that in 2012 in the United States, the estimated cost of preeclampsia within the first 12 months of delivery was $2.18 billion ($1.03 billion for women and $1.15 billion for infants), which was disproportionately borne by premature births (5). This Practice Bulletin will provide guidelines for the diagnosis and management of gestational hypertension and preeclampsia.
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The concept that preeclampsia is a multisystemic syndrome is appreciated in both research and clinical care. Our understanding of pathophysiology recognizes the role of inflammation, oxidative and endoplasm reticulum stress, and angiogenic dysfunction. Yet, we have not progressed greatly toward clinically useful prediction nor had substantial success in prevention or treatment. One possibility is that the maternal syndrome may be reached through different pathophysiological pathways, that is, subtypes of preeclampsia, that in their specificity yield more clinical utility. For example, early and late onset preeclampsia are increasingly acknowledged as different pathophysiological processes leading to a common presentation. Other subtypes of preeclampsia are supported by disparate clinical outcomes, long-range prognosis, organ systems involved, and risk factors. These insights have been supplemented by discovery-driven methods, which cluster preeclampsia cases into groups indicating different pathophysiologies. In this presentation, we review likely subtypes based on current knowledge and suggest others. We present a consideration of the requirements for a clinically meaningful preeclampsia subtype. A useful subtype should (1) identify a specific pathophysiological pathway or (2) specifically indicate maternal or fetal outcome, (3) be recognizable in a clinically useful time frame, and (4) these results should be reproducible and generalizable (but at varying frequency) including in low resource settings. We recommend that the default consideration be that preeclampsia includes several subtypes rather than trying to force all cases into a single pathophysiological pathway. The recognition of subtypes and deciphering their different pathophysiologies will provide specific targets for prevention, prediction, and treatment directing personalized care.
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To establish gestational phase adapted cutoffs for the use of the soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio as a diagnostic tool for preeclampsia in the clinical setting, a multicenter case-control study including a total of 1149 patients was performed. We report normal values of sFlt-1, PlGF, and the sFlt-1/PlGF ratio based on the analysis of a total of 877 patients with uneventful pregnancy outcome. A total of 234 patients with preeclampsia and a matched cohort consisting of 468 patients with normal pregnancy outcome were compared, and sFlt-1 and PlGF were measured on an automated platform. Separate cutoffs for the sFlt-1/PlGF ratio were determined for the early (20+0-33+6 weeks) and the late gestational phase (34+0 weeks-delivery). For each of the 2 gestational phases, 2 independent cutoffs framing an equivocal zone were determined: the first cutoff with focus on high sensitivity, and the second focusing on high specificity. Between 20+0 and 33+6 weeks, the cutoffs at ≤33 and ≥85 resulted in a sensitivity/specificity of 95%/94% and 88%/99.5%, respectively. An sFlt-1/PlGF ratio of ≤33 had the lowest likelihood of a negative test (0.05; 95% confidence interval, 0.02-0.13), whereas values ≥85 had the highest likelihood of a positive test (176; 95% confidence interval, 24.88-1245). After 34+0 weeks, the cutoffs at ≤33 and ≥110 yielded a sensitivity/specificity of 89.6%/73.1% and 58.2%/95.5%, respectively. The approach to use multiple cutoffs for the early and late gestational phase enhances the diagnostic accuracy of the sFlt-1/PlGF ratio as a diagnostic tool for preeclampsia.
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中华医学会妇产科学分会妊娠期高血压疾病学组. 妊娠期高血压疾病诊治指南(2020)[J]. 中华妇产科杂志, 2020, 55(4):227-238. DOI:10.3760/cma.j.cn112141-20200114-00039.
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The ratio of maternal serum sFlt-1 (soluble fms-like tyrosine kinase 1) to PlGF (placental growth factor) has been used retrospectively to rule out the occurrence of preeclampsia, a pregnancy hypertensive disorder, within 7 days in women presenting with clinical suspicion of preeclampsia. A prospective, interventional, parallel-group, randomized clinical trial evaluated the use of sFlt-1/PlGF ratio in women presenting with suspected preeclampsia. Women were assigned to reveal (sFlt-1/PlGF result known to clinicians) or nonreveal (result unknown) arms. A ratio cutoff of 38 was used to define low (≤38) and elevated risk (>38) of developing the condition in the subsequent week. The primary end point was hospitalization within 24 hours of the test. Secondary end points were development of preeclampsia and other adverse maternal-fetal outcomes. We recruited 370 women (186 reveal versus 184 nonreveal). Preeclampsia occurred in 85 women (23%). The number of admissions was not significantly different between groups (n=48 nonreveal versus n=60 reveal; =0.192). The reveal trial arm admitted 100% of the cases that developed preeclampsia within 7 days, whereas the nonreveal admitted 83% (=0.038). Use of the test yielded a sensitivity of 100% (95% CI, 85.8-100) and a negative predictive value of 100% (95% CI, 97.1-100) compared with a sensitivity of 83.3 (95% CI, 58.6-96.4) and negative predictive value of 97.8 (95% CI, 93.7-99.5) with clinical practice alone. Use of the sFlt-1/PlGF ratio significantly improved clinical precision without changing the admission rate. Clinical Trial Registration- URL: http://www.isrctn.com. Unique identifier: ISRCTN87470468.
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This retrospective real-world study investigated the clinical use of the sFlt-1 (soluble fms-like tyrosine kinase 1)/PlGF (placental growth factor) ratio alone or in combination with other clinical tests to predict an adverse maternal (maternal death, kidney failure, hemolysis elevated liver enzymes low platelets-syndrome, pulmonary edema, disseminated intravascular coagulation, cerebral hemorrhage, or eclampsia) or fetal (delivery before 34 weeks because of preeclampsia and/or intrauterine growth restriction, respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage, placental abruption or intrauterine fetal death or neonatal death within 7 days post natum) pregnancy outcome in patients with signs and symptoms of preeclampsia. We evaluated the sFlt-1/PlGF-ratio cutoff values of 38 and 85 and evaluated its integration into a multimarker model. Of 1117 subjects, 322 (28.8%) developed an adverse fetal or maternal outcome. Patients with an adverse versus no adverse outcome had a median sFlt-1/PlGF-ratio of 177 (interquartile range, 54-362) versus 14 (4-64). Risk-stratification with the sFlt-1/PlGF cutoff values into high- (>85), intermediate- (38-85), and low-risk (<38) showed a significantly shorter time to delivery in high- and intermediate- versus low-risk patients (4 versus 8 versus 29 days). When integrating all available clinical information into a multimarker model, an area under the curve of 88.7% corresponding to a sensitivity, specificity, positive and negative predictive value of 80.0%, 87.3%, 75.0%, and 90.2% was reached. The sFlt-1/PlGF-ratio alone was inferior to the full model with an area under the curve of 85.7%. As expected, blood pressure and proteinuria were significantly less accurate with an area under the curve of 69.0%. Combining biomarker measurements with all available information in a multimarker modeling approach increased detection of adverse outcomes in women with suspected disease.
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To systematically review the performance of soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and the sFlt-1/PlGF ratio in predicting adverse outcomes in women with preeclampsia.We performed a systematic search of MEDLINE, EMBASE, CINAHL, Cochrane, Scopus, ClinicalTrials.gov, and Emcare databases from 1989 to March 2019 to identify studies correlating sFlt-1, PlGF, and the sFlt-1/PlGF ratio with the occurrence of adverse outcomes in women with preeclampsia.Two independent reviewers screened 3,194 studies using Covidence. Studies were included if they examined the performance of sFLT-1, PlGF, or the sFLT-1/PlGF ratio in predicting adverse outcomes in women with suspected or confirmed preeclampsia.We extracted contingency tables with true-positive, false-positive, true-negative, and false-negative results. We calculated sensitivity, specificity, diagnostic odds ratios, and area under the summary receiver operating characteristic curve (area sROC) through a bivariate mixed-effects meta-analysis. Our literature search identified 3,194 articles, of which 33 (n=9,426 patients) were included. There was significant variation in the included studies with regard to the biomarkers and outcomes assessed. As such, few studies (n=4-8) were included in the meta-analysis component with significant heterogeneity between studies (I2=33-99). Nonetheless, both PlGF and the sFlt-1/PlGF ratio demonstrated area sROC values between 0.68 and 0.87 for the prediction of composite adverse maternal and perinatal outcomes, preterm birth and fetal growth restriction.Placental growth factor and the sFlt-1/PlGF ratio show prognostic promise for adverse outcomes in preeclampsia, but study heterogeneity limits their clinical utility.PROSPERO, CRD42019136207.Copyright © 2020 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.
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Pre-eclampsia is a life-threatening disease of pregnancy unique to humans and a leading cause of maternal and neonatal morbidity and mortality. Women who survive pre-eclampsia have reduced life expectancy, with increased risks of stroke, cardiovascular disease and diabetes, while babies from a pre-eclamptic pregnancy have increased risks of preterm birth, perinatal death and neurodevelopmental disability and cardiovascular and metabolic disease later in life. Pre-eclampsia is a complex multisystem disease, diagnosed by sudden-onset hypertension (>20 weeks of gestation) and at least one other associated complication, including proteinuria, maternal organ dysfunction or uteroplacental dysfunction. Pre-eclampsia is found only when a placenta is or was recently present and is classified as preterm (delivery <37 weeks of gestation), term (delivery ≥37 weeks of gestation) and postpartum pre-eclampsia. The maternal syndrome of pre-eclampsia is driven by a dysfunctional placenta, which releases factors into maternal blood causing systemic inflammation and widespread maternal endothelial dysfunction. Available treatments target maternal hypertension and seizures, but the only 'cure' for pre-eclampsia is delivery of the dysfunctional placenta and baby, often prematurely. Despite decades of research, the aetiology of pre-eclampsia, particularly of term and postpartum pre-eclampsia, remains poorly defined. Significant advances have been made in the prediction and prevention of preterm pre-eclampsia, which is predicted in early pregnancy through combined screening and is prevented with daily low-dose aspirin, starting before 16 weeks of gestation. By contrast, the prediction of term and postpartum pre-eclampsia is limited and there are no preventive treatments. Future research must investigate the pathogenesis of pre-eclampsia, in particular of term and postpartum pre-eclampsia, and evaluate new prognostic tests and treatments in adequately powered clinical trials.© 2023. Springer Nature Limited.
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所有作者均声明不存在利益冲突
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