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Mapping the Theories of Preeclampsia and the Role of Angiogenic Factors

A Systematic Review

From the¹ United Nations Development Programme, United Nations Population Fund, World Health Organization, World Bank Special Programme of Research, Development and Research Training in Human Reproduction, and Department of Reproductive Health and Research, World Health Organization, Geneva, Switzerland; Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford, United Kingdom; ²Mario Negri Institute for Pharmacological Research, Bergamo, Italy; ³Centro de Estudios e Investigación en Salud, Department of Obstetrics and Gynecology, Fundación Santa Fé de Bogota, Bogota, Colombia; ⁴Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts; and ⁵Department of Obstetrics and Gynecology and Medicine, the University of Chicago, Chicago, Illinois.

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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