Mapping the Theories of Preeclampsia and the Role of Angiogenic Factors: A Systematic Review

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OBJECTIVE:To evaluate claims that elevated soluble fms-like tyrosine kinase-1 receptor (sFlt-1) and decreased placental growth factor predict preeclampsia.DATA SOURCES:MEDLINE (1966–March 2006), EMBASE (1980–June 2006), POPLINE (1980–June 2006), CINAHL (1982–June 2006), and LILACS (1982–June 2006) were searched, and experts contacted.METHODS OF STUDY SELECTION:Studies identified and included were those reporting blood and urine levels of sFlt-1 or placental growth factor obtained before gestational week 30 or overt preeclampsia.TABULATION, INTEGRATION, AND RESULTS:Ten of 184 available studies analyzing sFlt-1 and 14 of 319 studies analyzing placental growth factor were included in this review. There was considerable interreport heterogeneity in methodology and results for sFlt-1 measured before gestational week 25. After week 25 placental growth factor and sFlt-1 levels varied consistently between the normal pregnancy group and women destined to develop preeclampsia, achieving significance in women who developed severe preeclampsia.CONCLUSION:Third-trimester increases in sFlt-1 and decreases in placental growth factor levels are associated with preeclampsia, specifically severe disease, based on retrospective data. The evidence is insufficient to recommend these markers to be used for screening, and prospective studies employing rigorous laboratory and study design criteria are needed to determine the clinical usefulness of these tests.

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