sFlt‐1/PlGF for prediction of early‐onset pre‐eclampsia: STEPS (Study of Early Pre‐eclampsia in Spain)

Perales, Alfredo; Delgado, Juan Luis; Calle, María de la; García-Hernández, José Ángel; Escudero, Ana I; Maza, José Manuel Campillos; Sarabia, María Desamparados; Laíz, Begoña; Duque, Marta; Navarro, Mercedes; Calmarza, Pilar; Hund, Martin; Álvarez, Francisco V.; investigators, Steps

doi:10.1002/uog.17373

Cited by 62 publications

(44 citation statements)

References 56 publications

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“…The onset of hypertension during pregnancy or worsening of pre-existing chronic hypertension without proteinuria represents a complex situation, in which it is essential to rule out PE. Verlohren et al [ 17 ] showed that the sFlt-1/PlGF ratio in patients with PE is significantly higher compared with that in patients with chronic and gestational hypertension. These data, recently confirmed in a Spanish cohort [ 17 ], demonstrated the role of the sFlt-1/PlGF ratio in differentiating PE and other pregnancy-related hypertensive disorders [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of sFlt-1/PlGF Ratio for Predicting and Improving Clinical Management of Pre-eclampsia: Experience in a Specialized Perinatal Care Center

et al. 2018

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BackgroundManagement of pregnant women at high risk of pre-eclampsia (PE) requires frequent monitoring, with referral to specialized perinatal care centers. Reliable tests are necessary to improve prediction of PE and related complications and to assess disease severity and progression. An imbalance in two biomarkers, soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF), is involved in PE pathogenesis. The sFlt-1 to PlGF ratio is increased in pregnant women before the onset of PE. An elevated ratio is highly predictive of PE, whereas the diagnosis of PE can be ruled out within one week for low ratios. The main objective of this study was to assess whether a low sFlt-1/PlGF ratio, below a cutoff of 38, can predict the absence of PE within one week.MethodsWe performed a prospective, monocentric, observational study to evaluate serum sFlt-1/PlGF ratio (Roche Diagnostics Cobas e411 system) for predicting -PE in a group of 67 high-risk pregnant women (20–37 gestation weeks).ResultsAmong the 67 patients included, 53 had a sFlt-1/PlGF ratio lower than 38; none developed subsequent PE leading to a negative predictive value of 100%. Eight patients developed clinical PE. The positive predictive value was 21% at one week and 18% at four weeks, in accordance with previous studies.ConclusionsThe serum sFlt-1/PlGF ratio showed highly predictive performances for ruling out PE. Using these biomarkers in routine management of PE may improve clinical care and avoid inappropriate hospitalization, which has a significant economic impact.

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Section: Discussionmentioning

confidence: 99%

Evaluation of sFlt-1/PlGF Ratio for Predicting and Improving Clinical Management of Pre-eclampsia: Experience in a Specialized Perinatal Care Center

et al. 2018

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“…These include placental growth factor (PlGF), soluble vascular endothelial growth factor receptor 1, endoglin, and their ratios [55,58,65,82,109,113–117]. Prediction models have also been developed that combine maternal blood pressure, uterine artery Doppler, PlGF [99,101,118–124], pregnancy-associated plasma protein A, and inhibin-A [125].…”

Section: Introductionmentioning

confidence: 99%

The prediction of late-onset preeclampsia: Results from a longitudinal proteomics study

et al. 2017

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BackgroundLate-onset preeclampsia is the most prevalent phenotype of this syndrome; nevertheless, only a few biomarkers for its early diagnosis have been reported. We sought to correct this deficiency using a high through-put proteomic platform.MethodsA case-control longitudinal study was conducted, including 90 patients with normal pregnancies and 76 patients with late-onset preeclampsia (diagnosed at ≥34 weeks of gestation). Maternal plasma samples were collected throughout gestation (normal pregnancy: 2–6 samples per patient, median of 2; late-onset preeclampsia: 2–6, median of 5). The abundance of 1,125 proteins was measured using an aptamers-based proteomics technique. Protein abundance in normal pregnancies was modeled using linear mixed-effects models to estimate mean abundance as a function of gestational age. Data was then expressed as multiples of-the-mean (MoM) values in normal pregnancies. Multi-marker prediction models were built using data from one of five gestational age intervals (8–16, 16.1–22, 22.1–28, 28.1–32, 32.1–36 weeks of gestation). The predictive performance of the best combination of proteins was compared to placental growth factor (PIGF) using bootstrap.Results1) At 8–16 weeks of gestation, the best prediction model included only one protein, matrix metalloproteinase 7 (MMP-7), that had a sensitivity of 69% at a false positive rate (FPR) of 20% (AUC = 0.76); 2) at 16.1–22 weeks of gestation, MMP-7 was the single best predictor of late-onset preeclampsia with a sensitivity of 70% at a FPR of 20% (AUC = 0.82); 3) after 22 weeks of gestation, PlGF was the best predictor of late-onset preeclampsia, identifying 1/3 to 1/2 of the patients destined to develop this syndrome (FPR = 20%); 4) 36 proteins were associated with late-onset preeclampsia in at least one interval of gestation (after adjustment for covariates); 5) several biological processes, such as positive regulation of vascular endothelial growth factor receptor signaling pathway, were perturbed; and 6) from 22.1 weeks of gestation onward, the set of proteins most predictive of severe preeclampsia was different from the set most predictive of the mild form of this syndrome.ConclusionsElevated MMP-7 early in gestation (8–22 weeks) and low PlGF later in gestation (after 22 weeks) are the strongest predictors for the subsequent development of late-onset preeclampsia, suggesting that the optimal identification of patients at risk may involve a two-step diagnostic process.

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“…al, in their study using the same ratio found that 19.64% developed preeclampsia. 12 They also reported that 35.5% study participants with history of preeclampsia in previous pregnancy developed early onset preeclampsia. These results differ from that of the current study, where 48.6% had early onset preeclampsia.…”

Section: Sensitivity Specificitymentioning

confidence: 96%

“…While in a similar study conducted by Perales A et al, found that sFlt-1/Plgf ratio was better predictor for preeclampsia than uterine artery doppler pulsatility index with sensitivity and specificity of 91.1% and 82% respectively similar to our study. 12 Taraseviciene V et al in the study on prediction of preeclampsia found that sensitivity and specificity of sFlt-1/Plgf was 95.8% and 96.2% respectively. 14…”

Section: Sensitivity Specificitymentioning

confidence: 97%

Comparative study of sFlt-1/Plgf ratio with uterine artery doppler indices in prediction of preeclampsia at 22-24 weeks period of gestation

Gupta

Sharma

Arora

et al. 2020

Int J Reprod Contracept Obstet Gynecol

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Background: Hypertensive disorders like pre-eclampsia along with hemorrhage and infection, contributes greatly to maternal morbidity and mortality. Various pro and antiangiogenic factors like sFlt-1 and Plgf have been linked to the etiopathogenesis of placental vascular disease and their combination with uterine artery doppler studies may improve the prediction accuracy. Present study was conducted to analyze sFlt-1/Plgf ratio and uterine artery doppler indices among high risk patients and to compare these in prediction of preeclampsia.Methods: A prospective observational study was conducted from September 2017 to February 2019 in which 100 patients giving consent and satisfying inclusion criteria were evaluated for various risk factors and were subjected to sFlt-1/Plgf ratio test and uterine artery doppler study at 22-24 weeks period of gestation. They were followed up and maternal outcome was analysed.Results: Among the cohort of 100 women with high risk factors, 35% of the study participants developed pre-eclampsia. Using sFlt-1/Plgf ratio 40% of them were screened positive for pre-eclampsia. This percentage of screened positive was 40%, 43%, and 53% using uterine artery RI, PI, and SD respectively. sFlt-1/Plgf was found to have a sensitivity of 91.4% and specificity of 87.7%. ROC curve analysis showed highest area under curve (AUC) for sFlt-1/Plgf (0.858).Conclusions: sFlt-1/Plgf ratio was found to be a better predictable biomarker than uterine artery Doppler indices in prediction of pre-eclampsia at 22-24 weeks period of gestation.

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sFlt‐1/PlGF for prediction of early‐onset pre‐eclampsia: STEPS (Study of Early Pre‐eclampsia in Spain)

Cited by 62 publications

References 56 publications

Evaluation of sFlt-1/PlGF Ratio for Predicting and Improving Clinical Management of Pre-eclampsia: Experience in a Specialized Perinatal Care Center

Evaluation of sFlt-1/PlGF Ratio for Predicting and Improving Clinical Management of Pre-eclampsia: Experience in a Specialized Perinatal Care Center

The prediction of late-onset preeclampsia: Results from a longitudinal proteomics study

Comparative study of sFlt-1/Plgf ratio with uterine artery doppler indices in prediction of preeclampsia at 22-24 weeks period of gestation

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