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Circulating angiogenic factors and the risk of preeclampsia.

Richard J Levine1, Sharon E Maynard, Cong Qian

  • 1Division of Epidemiology, Statistics, and Prevention Research, National Institute of Child Health and Human Development, Department of Health and Human Services, Bethesda, MD 20892, USA. levinerj@mail.nih.gov

The New England Journal of Medicine
|February 7, 2004

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View abstract on PubMed

Summary

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  • Biomedical And Clinical Sciences
  • Oncology And Carcinogenesis
  • Predictive And Prognostic Markers
  • Circulating Angiogenic Factors And The Risk Of Preeclampsia.
    • This summary is machine-generated.

    Elevated soluble fms-like tyrosine kinase 1 (sFlt-1) and reduced placental growth factor (PlGF) levels in pregnancy predict the development of preeclampsia. These angiogenic factor changes occur weeks before clinical symptoms appear.

    Area of Science:

    • Obstetrics and Gynecology
    • Maternal-Fetal Medicine
    • Cardiovascular Biology

    Background:

    • The etiology of preeclampsia, a pregnancy complication, is not fully understood.
    • Emerging evidence suggests a role for dysregulation of angiogenic factors, specifically elevated soluble fms-like tyrosine kinase 1 (sFlt-1).

    Purpose of the Study:

    • To investigate the predictive value of serum concentrations of angiogenic factors, including total sFlt-1, free placental growth factor (PlGF), and free vascular endothelial growth factor (VEGF), for preeclampsia development.
    • To analyze these changes in relation to gestational age and proximity to preeclampsia onset.

    Main Methods:

    • A nested case-control study was conducted within the Calcium for Preeclampsia Prevention trial.
    • 120 pairs of healthy nulliparous women (preeclampsia cases matched with normotensive controls) were analyzed.
    • Serum samples collected throughout pregnancy were assayed for sFlt-1, PlGF, and VEGF levels and analyzed cross-sectionally.

    Main Results:

    • In normotensive pregnancies, sFlt-1 levels increased and PlGF levels decreased in the last two months.
    • These angiogenic factor alterations occurred earlier and were more pronounced in women who later developed preeclampsia, with sFlt-1 elevation starting ~5 weeks prior.
    • Significantly lower PlGF levels were detected 13-16 weeks before preeclampsia onset, with greater changes observed in early-onset preeclampsia and cases associated with small-for-gestational-age infants.

    Conclusions:

    • Increased serum sFlt-1 and decreased serum PlGF levels are significant predictors of subsequent preeclampsia development.
    • These angiogenic biomarker changes precede the clinical manifestation of preeclampsia, offering potential for early detection.

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