Circulating Angiogenic Factors and the Risk of Preeclampsia

Richard J. Levine, Sharon E. Maynard, Cong Qian, Kee Hak Lim, Lucinda J. England, Kai F. Yu, Enrique F. Schisterman, Ravi Thadhani, Benjamin P. Sachs, Franklin H. Epstein, Baha M. Sibai, Vikas P. Sukhatme, S. Ananth Karumanchi

Research output: Contribution to journalArticlepeer-review


BACKGROUND: The cause of preeclampsia remains unclear. Limited data suggest that excess circulating soluble fms-like tyrosine kinase 1 (sFlt-1), which binds placental growth factor (PlGF) and vascular endothelial growth factor (VEGF), may have a pathogenic role. METHODS: We performed a nested case-control study within the Calcium for Preeclampsia Prevention trial, which involved healthy nulliparous women. Each woman with Preeclampsia was matched to one normotensive control. A total of 120 pairs of women were randomly chosen. Serum concentrations of angiogenic factors (total sFlt-1, free PlGF, and free VEGF) were measured throughout pregnancy; there were a total of 655 serum specimens. The data were analyzed cross-sectionally within intervals of gestational age and according to the time before the onset of preeclampsia. RESULTS: During the last two months of pregnancy in the normotensive controls, the level of srlt-1 increased and the level of PlGF decreased. These changes occurred earlier and were more pronounced in the women in whom preeclampsia later developed. The sFlt-1 level increased beginning approximately fire weeks before the onset of preeclampsia. At the onset of clinical disease, the mean serum level in the women with preeclampsia was 4382 pg per milliliter, as compared with 1643 pg per milliliter in controls with fetuses of similar gestational age (P

Original languageEnglish (US)
Pages (from-to)672-683
Number of pages12
JournalNew England Journal of Medicine
Issue number7
StatePublished - Mar 22 2004
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)


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