Abstract
Purpose
To systematically review the approach of using two independent sFlt-1/PlGF cutoffs that has better sensitivity (cutoff-sen) and specificity (cutoff-spe) separately for risk stratification in the detection of preeclampsia.
Methods
PubMed and Embase databases and reference lists were searched up to June 2016. Inclusion criteria were blood samples for sFlt-1/PlGF with separate cutoffs (cutoff-sen and cutoff-spe) provided. Six relevant studies were identified. Pooling of results was done based on three studies and a systematic review was performed based on all six.
Results
The strategy of using a cutoff of ≤33 and ≥85 for early onset preeclampsia, and ≤33 and ≥110 for the late onset preeclampsia was proposed and examined. The pooled sensitivity for cutoff-sen was: 95.3% (90.6–98.1%) and 88.6% (82.9–92.9%) for early and late onset preeclampsia, respectively. The pooled specificity for cutoff-spe was: 97.6% (95.2–98.9%) and 94.2% (91.4–96.3%) for early and late onset preeclampsia respectively. The pooled estimation of the early onset pre-eclamptic pregnancies and control normal pregnancies classified in the equivocal zone was 4.9% (2.0–8.8%) and 32.4% (25.7–39.5%), respectively, and 26.8% (10.3–47.6%) and 8.7% (3.0–17.6%) for late onset patients.
Conclusion
The new dual-cutoff diagnostic system optimizes the predictive performance of the single cutoff system. Further studies are required to assess the performance of this system and to define the approach and frequency at which subjects in the equivocal zone should be screened.
Similar content being viewed by others
References
Zeisler H, Llurba E, Chantraine F, Vatish M, Staff AC, Sennstrom M, Olovsson M, Brennecke SP, Stepan H, Allegranza D, Dilba P, Schoedl M, Hund M, Verlohren S (2016) Predictive Value of the sFlt-1:PlGF Ratio in Women with Suspected Preeclampsia. N Engl J Med 374(1):13–22. doi:10.1056/NEJMoa1414838
Stepan H, Hund M, Gencay M, Denk B, Dinkel C, Kaminski WE, Wieloch P, Semus B, Meloth T, Droge LA, Verlohren S (2016) A comparison of the diagnostic utility of the sFlt-1/PlGF ratio versus PlGF alone for the detection of preeclampsia/HELLP syndrome. Hypertens Pregnancy. doi:10.3109/10641955.2016.1141214
Powe CE, Levine RJ, Karumanchi SA (2011) Preeclampsia, a disease of the maternal endothelium: the role of antiangiogenic factors and implications for later cardiovascular disease. Circulation 123(24):2856–2869. doi:10.1161/CIRCULATIONAHA.109.853127
Villa PM, Hamalainen E, Maki A, Raikkonen K, Pesonen AK, Taipale P, Kajantie E, Laivuori H (2013) Vasoactive agents for the prediction of early- and late-onset preeclampsia in a high-risk cohort. BMC Pregnancy Childbirth 13:110. doi:10.1186/1471-2393-13-110
Verlohren S, Galindo A, Schlembach D, Zeisler H, Herraiz I, Moertl MG, Pape J, Dudenhausen JW, Denk B, Stepan H (2010) An automated method for the determination of the sFlt-1/PIGF ratio in the assessment of preeclampsia. Am J Obstetr Gynecol 202(2):161, e161–161, e111. doi:10.1016/j.ajog.2009.09.016
Sunderji S, Gaziano E, Wothe D, Rogers LC, Sibai B, Karumanchi SA, Hodges-Savola C (2010) Automated assays for sVEGF R1 and PlGF as an aid in the diagnosis of preterm preeclampsia: a prospective clinical study. Am J Obstetr Gynecol 202(1):40 e41–47. doi:10.1016/j.ajog.2009.07.025
Stepan H, Unversucht A, Wessel N, Faber R (2007) Predictive value of maternal angiogenic factors in second trimester pregnancies with abnormal uterine perfusion. Hypertension 49(4):818–824. doi:10.1161/01.HYP.0000258404.21552.a3
Álvarez-Fernández I, Prieto B, Rodríguez V, Ruano Y, Escudero AI, Álvarez FV (2014) New biomarkers in diagnosis of early onset preeclampsia and imminent delivery prognosis. Clin Chem Lab Med (CCLM). doi:10.1515/cclm-2013-0901
Verlohren S, Herraiz I, Lapaire O, Schlembach D, Zeisler H, Calda P, Sabria J, Markfeld-Erol F, Galindo A, Schoofs K, Denk B, Stepan H (2014) New gestational phase-specific cutoff values for the use of the soluble fms-like tyrosine kinase-1/placental growth factor ratio as a diagnostic test for preeclampsia. Hypertension 63(2):346–352. doi:10.1161/hypertensionaha.113.01787
Andersen LB, Frederiksen-Moller B, Work Havelund K, Dechend R, Jorgensen JS, Jensen BL, Nielsen J, Lykkedegn S, Barington T, Christesen HT (2015) Diagnosis of preeclampsia with soluble Fms-like tyrosine kinase 1/placental growth factor ratio: an inter-assay comparison. JASH 9(2):86–96. doi:10.1016/j.jash.2014.11.008
van Helden J, Weiskirchen R (2015) Analytical evaluation of the novel soluble fms-like tyrosine kinase 1 and placental growth factor assays for the diagnosis of preeclampsia. Clin Biochem 48(16–17):1113–1119. doi:10.1016/j.clinbiochem.2015.06.020
Schiettecatte J, Russcher H, Anckaert E, Mees M, Leeser B, Tirelli AS, Fiedler GM, Luthe H, Denk B, Smitz J (2010) Multicenter evaluation of the first automated Elecsys sFlt-1 and PlGF assays in normal pregnancies and preeclampsia. Clin Biochem 43(9):768–770. doi:10.1016/j.clinbiochem.2010.02.010
Liu Y, Zhao Y, Yu A, Zhao B, Gao Y, Niu H (2015) Diagnostic accuracy of the soluble Fms-like tyrosine kinase-1/placental growth factor ratio for preeclampsia: a meta-analysis based on 20 studies. Arch Gynecol Obstet 292(3):507–518. doi:10.1007/s00404-015-3671-8
Levine RJ, Lam C, Qian C, Yu KF, Maynard SE, Sachs BP, Sibai BM, Epstein FH, Romero R, Thadhani R, Karumanchi SA (2006) Soluble endoglin and other circulating antiangiogenic factors in preeclampsia. N Engl J Med 355(10):992–1005. doi:10.1056/NEJMoa055352
Hirashima C, Ohkuchi A, Arai F, Takahashi K, Suzuki H, Watanabe T, Kario K, Matsubara S, Suzuki M (2005) Establishing reference values for both total soluble Fms-like tyrosine kinase 1 and free placental growth factor in pregnant women. Hypertens Res 28(9):727–732. doi:10.1291/hypres.28.727
Saito S, Nakashima A (2014) A review of the mechanism for poor placentation in early-onset preeclampsia: the role of autophagy in trophoblast invasion and vascular remodeling. J Reprod Immunol 101–102:80–88. doi:10.1016/j.jri.2013.06.002
Wolf M, Shah A, Lam C, Martinez A, Smirnakis KV, Epstein FH, Taylor RN, Ecker JL, Karumanchi SA, Thadhani R (2005) Circulating levels of the antiangiogenic marker sFLT-1 are increased in first versus second pregnancies. Am J Obstet Gynecol 193(1):16–22. doi:10.1016/j.ajog.2005.03.016
Weissgerber TL, Roberts JM, Jeyabalan A, Powers RW, Lee M, Datwyler SA, Gandley RE (2012) Haptoglobin phenotype, angiogenic factors, and preeclampsia risk. Am J Obstetr Gynecol 206(4):358 e310–358. doi:10.1016/j.ajog.2012.01.009
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
This article does not contain any studies with human participants or animals performed by any of the authors.
Additional information
M. Zhao and Z. Zhu are contributed equally to the work.
Rights and permissions
About this article
Cite this article
Zhao, M., Zhu, Z., Liu, C. et al. Dual-cutoff of sFlt-1/PlGF ratio in the stratification of preeclampsia: a systematic review and meta-analysis. Arch Gynecol Obstet 295, 1079–1087 (2017). https://doi.org/10.1007/s00404-017-4302-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00404-017-4302-3