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Article

Pro- and Anti-Angiogenic Markers as Clinical Tools for Suspected Preeclampsia with and without FGR near Delivery—A Secondary Analysis

1
Institute of Clinical Chemistry and Biochemistry, University Medical Centre, Njegoševa 4, 1000 Ljubljana, Slovenia
2
Faculty of Pharmacy, University of Ljubljana, cesta 7, 1000 Ljubljana, Slovenia
3
Ziv Medical Center, Department of Statistics, Safed 7404703, Israel
4
Department of Statistics, Tel Hai Academic College, Tel Hai 12210, Israel
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Department of Perinatology, Division of Obstetrics and Gynecology, University Medical Center, Zaloška Cesta 2, 1000 Ljubljana, Slovenia
6
Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia
7
Women’s Hospital, Prečna ulica 4, 6230 Postojna, Slovenia
8
TeleMarpe Ltd., 41 Beit El St., Tel Aviv 6908742, Israel
9
The Fetal Medicine Research Institute, King’s College Hospital, 16-20 Windsor Walk, London SE5 8BB, UK
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Reprod. Med. 2021, 2(1), 12-25; https://doi.org/10.3390/reprodmed2010003
Received: 19 December 2020 / Revised: 31 January 2021 / Accepted: 2 February 2021 / Published: 8 February 2021
(This article belongs to the Special Issue Preeclampsia: Pathogenesis, Diagnosis and Treatment)
Objective—the objective of this study was to assess the accuracy of placental growth factor (PlGF), soluble Fms-like Tyrosine Kinase 1 (sFlt-1), and endoglin (sEng) in the diagnosis of suspected preeclampsia (PE) with and without fetal growth restriction (FGR) near delivery. Methods—this is a secondary analysis of a dataset of 125 pregnant women presenting at the high risk pregnancy clinic with suspected PE, FGR or PE + FGR in the University Medical Center of Slovenia. The dataset included 31 PE cases, 16 FGR cases, 42 PE + FGR cases, 15 cases who developed with unrelated complications before 37 weeks (wks) (PTD), and 21 unaffected controls who delivered a healthy baby at term. We also analyzed a sub-group of women who delivered early (<34 wks) including 10 PE, 12 FGR, 28 PE + FGR, and six PTD. Clinical management adhered to hospital guidelines. Marker levels were extracted from the dataset and were used to develop Receiver Operating Characteristic (ROC) curves and to calculate the area under the curve (AUC), the detection rates (DRs), and the false positive rates (FPRs). Previously published marker cutoffs for yes/no admission to hospital wards were extracted from the literature. Negative and positive predictive values (NPVs and PPVs) were evaluated for their value in determining whether hospital admission was required. Non-parametric tests were applied for statistical analysis; p < 0.05 was considered significant. Results—near delivery, all the pro-and anti-angiogenic markers provided diagnostic (ROC = 1.00) accuracy for the early (<34 wks) group of FGR. Diagnostic or near diagnostic (ROC = 0.95) accuracy was achieved by all marker for early PE + FGR but lower accuracy was achieved for early PE. For all cases, all markers, especially PlGF reached diagnostic or near diagnostic accuracy for FGR and PE + FGR. At this accuracy level, they can contribute to the clinical management of FGR, and PE + FGR. All the markers were less accurate for all PE cases. The use of published cutoffs was adequate for clinical management of FGR, whether early or for all cases, using an NPV > 90%. For PE + FGR, the PPV value approached 100%, especially for early cases, and can thus be implemented in clinical management. Neither NPV nor PPV were high enough for managing all cases of PE. There was no added value in measuring the PlGF/(sFlt-1 + sEng) ratio. Conclusion—This is the first study on a Slovenian population. It shows that near-delivery angiogenic biomarkers tests may be useful for confirming the diseases in cases where there is a diagnostic doubt. However, the clinical use of the biomarkers needs to be weighed against resources available and degree of certainty of the diagnosis made with and without them for managing suspected FGR and PE + FGR requiring delivery <34 wks, where they are very accurate, and furthermore in the management of all cases of FGR and FGR+PE. The markers were less accurate for the clinical diagnosis of PE. View Full-Text
Keywords: preeclampsia; FGR; PTD; sFlt-1; sEng; PlGF; VEGF; pro- and anti-angiogenic markers; area under the curve (AUC); PPV; NPV; detection rate (DR); false positive rate (FPR) preeclampsia; FGR; PTD; sFlt-1; sEng; PlGF; VEGF; pro- and anti-angiogenic markers; area under the curve (AUC); PPV; NPV; detection rate (DR); false positive rate (FPR)
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MDPI and ACS Style

Kumer, K.; Sharabi-Nov, A.; Fabjan Vodušek, V.; Premru Sršen, T.; Tul, N.; Fabjan, T.; Meiri, H.; Nicolaides, K.H.; Osredkar, J. Pro- and Anti-Angiogenic Markers as Clinical Tools for Suspected Preeclampsia with and without FGR near Delivery—A Secondary Analysis. Reprod. Med. 2021, 2, 12-25. https://doi.org/10.3390/reprodmed2010003

AMA Style

Kumer K, Sharabi-Nov A, Fabjan Vodušek V, Premru Sršen T, Tul N, Fabjan T, Meiri H, Nicolaides KH, Osredkar J. Pro- and Anti-Angiogenic Markers as Clinical Tools for Suspected Preeclampsia with and without FGR near Delivery—A Secondary Analysis. Reproductive Medicine. 2021; 2(1):12-25. https://doi.org/10.3390/reprodmed2010003

Chicago/Turabian Style

Kumer, Kristina, Adi Sharabi-Nov, Vesna Fabjan Vodušek, Tanja Premru Sršen, Nataša Tul, Teja Fabjan, Hamutal Meiri, Kypros H. Nicolaides, and Joško Osredkar. 2021. "Pro- and Anti-Angiogenic Markers as Clinical Tools for Suspected Preeclampsia with and without FGR near Delivery—A Secondary Analysis" Reproductive Medicine 2, no. 1: 12-25. https://doi.org/10.3390/reprodmed2010003

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