Biomarkers and the Prediction of Adverse Outcomes in Preeclampsia: A Systematic Review and Meta-analysis

Sean Lim, Wentao Li* (Corresponding Author), Jessica Kemper, Andrew Nguyen, Ben Willem Mol, Maya Reddy

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)

Abstract

OBJECTIVE: 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 SOURCES: We 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 SELECTION: Two 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 RESULTS: We 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. CONCLUSION: Placental growth factor and the sFlt-1/PlGF ratio show prognostic promise for adverse outcomes in preeclampsia, but study heterogeneity limits their clinical utility. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42019136207.

Original languageEnglish
Pages (from-to)72-81
Number of pages10
JournalObstetrics and Gynecology
Volume137
Issue number1
DOIs
Publication statusPublished - 1 Jan 2021

Bibliographical note

Financial Disclosure
Ben Willem Mol disclosed that money was paid to him from ObsEva, Guerbet,
Merck, and iGenomix. The other authors did not report any potential conflicts of
interest.

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