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 results: We 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% false-positive 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.