Accuracy of circulating placental growth factor, vascular endothelial growth factor, soluble fms‐like tyrosine kinase 1 and soluble endoglin in the prediction of pre‐eclampsia: a systematic review and meta‐analysis

Abstract

Background Biomarkers have been proposed for identification of women at increased risk of developing pre-eclampsia.Objectives To investigate the capacity of circulating placental growth factor (PlGF), vascular endothelial growth factor (VEGF), soluble fms-like tyrosine kinase-1 (sFLT1) and soluble endoglin (sENG) to predict pre-eclampsia.Search strategy Medline and Embase through October 2010 and reference lists of reviews, without constraints.Selection criteria We included original publications on testing of PlGF, VEGF, sFLT1 and sENG in serum or plasma of pregnant women at <30 weeks of gestation and before clinical onset of pre-eclampsia.Data collection and analysis Two reviewers independently identified eligible studies, extracted descriptive and test accuracy data and assessed methodological quality. Summary estimates of discriminatory performance were obtained. Main resultsWe included 34 studies. Concentrations of PlGF (27 studies) and VEGF (three studies) were lower in women who developed pre-eclampsia: standardised mean differences (SMD) )0.56 (95% CI )0.77 to )0.35) and )1.25 (95% CI )2.73 to 0.23). Concentrations of sFLT1 (19 studies) and sENG (ten studies) were higher: SMD 0.48 (95% CI 0.21-0.75) and SMD 0.54 (95% CI 0.24-0.84). The summary diagnostic odds ratios were: PlGF 9.0 (95% CI 5.6-14.5), sFLT1 6.6 (95% CI 3.1-13.7), sENG 4.2 (95% CI 2.4-7.2), which correspond to sensitivities of 32%, 26% and 18%, respectively, for a 5% falsepositive rate.Author's conclusions PlGF, sFLT1 and sENG showed modest but significantly different concentrations before 30 weeks of gestation in women who developed pre-eclampsia. Test accuracies of all four markers, however, are too poor for accurate prediction of pre-eclampsia in clinical practice.Keywords Biomarkers, placental growth factor, pre-eclampsia, soluble endoglin, soluble fms-like tyrosine kinase-1, vascular endothelial growth factor.Please cite this paper as: Kleinrouweler C, Wiegerinck M, Ris-Stalpers C, Bossuyt P, van der Post J, von Dadelszen P, Mol B, Pajkrt E, for the EBM CON-NECT Collaboration. Accuracy of circulating placental growth factor, vascular endothelial growth factor, soluble fms-like tyrosine kinase 1 and soluble endoglin in the prediction of pre-eclampsia: a systematic review and meta-analysis. BJOG 2012;119:778-787.

Placenta-derived exosomes: potential biomarkers of preeclampsia

“…[43][44][45] Although sEng values alone or in combination with other pro-and antiangiogenic factors are significantly altered in PE serum, it has proven to be a poor biomarker of the disorder. 46 Cell-free fetal DNA cfDNA and cffDNA are also probable combined biomarkers of PE, mainly due to their sensitivity and specificity in biological fluids. 47,48 The identification of the methylated RASSF1A promoter gene, which is elevated in early-PE pregnancies, [49][50][51] offers a promising alternative to the quantification of cffDNA, using Y-chromosome-specific sequences.…”

How to assess and manage hypertension during and after pregnancy

“…Unfortunately, the markers so far investigated do not appear to have a high enough positive predictive value to use routinely in clinical practice [28]. A recent systematic review investigated levels of circulating PlGF, VEGF, sFlt1 and sEng in the serum and plasma of pregnant women prior to 30 weeks' gestation, but before clinical onset of pre-eclampsia [29]. Modest rises in PlGF, sFlt1 and sEng concentrations were all noted prior to 30 weeks' gestation in women who developed pre-eclampsia, but test accuracies for these markers remained too poor for accurate prediction of pre-eclampsia in clinical practice [29].…”

“…A recent systematic review investigated levels of circulating PlGF, VEGF, sFlt1 and sEng in the serum and plasma of pregnant women prior to 30 weeks' gestation, but before clinical onset of pre-eclampsia [29]. Modest rises in PlGF, sFlt1 and sEng concentrations were all noted prior to 30 weeks' gestation in women who developed pre-eclampsia, but test accuracies for these markers remained too poor for accurate prediction of pre-eclampsia in clinical practice [29]. The use of first or second trimester maternal uterine artery Doppler velocimetry has been extensively investigated both in isolation and in combination with routinely measured first trimester serum markers (e.g., b-hCG, PAPP-A, inhibin A and activin A) and maternal risk factor assessment [30].…”

Early Diagnosis of Preeclampsia

“…However, a recent systematic review that synthesized results of 34 studies calculated summary diagnostic odds ratios of PlGF 9.0 (95% CI 5.6-14.5), sFlt-1 6.6 (95% CI 3.1-13.7), and sEng 4.2 (95% CI 2.4-7.2), which correspond to sensitivities of 32%, 26%, and 18%, respectively. The authors concluded that the test accuracies of all four markers might be too poor for accurate prediction of preeclampsia in clinical practice [44]. To date, however, the antiangiogenic factor assays have been used to discriminate preeclampsia from other etiologies of renal compromise, and have proven useful in a variety of select clinical scenarios, including presumed glomerulonephritis [45], lupus [46], and in patients on hemodialysis [47].…”