Biomarkers and the prediction of adverse Ooutcomes in preeclampsia: a systematic review and meta-analysis

To systematically review the performance of soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and the sFlt-1/PlGF ratio in predicting adverse outcomes in women with preeclampsia.Data sourcesWe performed a systematic search of MEDLINE, EMBASE, CINAHL, Cochrane, Scopus, ClinicalTrials.gov, and Emcare databases from 1989 to March 2019 to identify studies correlating sFlt-1, PlGF, and the sFlt-1/PlGF ratio with the occurrence of adverse outcomes in women with preeclampsia.Methods of study selectionTwo independent reviewers screened 3,194 studies using Covidence. Studies were included if they examined the performance of sFLT-1, PlGF, or the sFLT-1/PlGF ratio in predicting adverse outcomes in women with suspected or confirmed preeclampsia.Tabulation, integration, and resultsWe extracted contingency tables with true-positive, false-positive, true-negative, and false-negative results. We calculated sensitivity, specificity, diagnostic odds ratios, and area under the summary receiver operating characteristic curve (area sROC) through a bivariate mixed-effects meta-analysis. Our literature search identified 3,194 articles, of which 33 (n=9,426 patients) were included. There was significant variation in the included studies with regard to the biomarkers and outcomes assessed. As such, few studies (n=4-8) were included in the meta-analysis component with significant heterogeneity between studies (I2=33-99). Nonetheless, both PlGF and the sFlt-1/PlGF ratio demonstrated area sROC values between 0.68 and 0.87 for the prediction of composite adverse maternal and perinatal outcomes, preterm birth and fetal growth restriction.ConclusionPlacental growth factor and the sFlt-1/PlGF ratio show prognostic promise for adverse outcomes in preeclampsia, but study heterogeneity limits their clinical utility.Sean Lim, Wentao Li, Jessica Kemper, Andrew Nguyen, Ben Willem Mol, Maya Redd