Soluble fms-Like tyrosine kinase 1 (sFlt1), endoglin and placental growth factor (PlGF) in preeclampsia among high risk pregnancies.
BACKGROUND
Differences in circulating concentrations of antiangiogenic factors sFlt1 and soluble endoglin (sEng) and the pro-angiogenic growth factor PlGF are reported to precede the onset of preeclampsia weeks to months in low-risk pregnant women. The objective of this study was to investigate whether similar changes can be detected in pregnant women at high-risk to develop the syndrome.


METHODS
This study is a secondary analysis of the NICHD MFMU trial of aspirin to prevent preeclampsia in high-risk pregnancies. Serum samples were available from 194 women with pre-existing diabetes, 313 with chronic hypertension, 234 with multifetal gestation, and 252 with a history of preeclampsia in a previous pregnancy. Samples collected across pregnancy were analyzed in a blinded fashion for sFlt1, sEng and PlGF.


RESULTS
The odds of developing preeclampsia were significantly increased among women with multiple fetuses for each 2-fold elevation in sFlt1, sEng and the ratio of angiogenic factors (e.g. OR 2.18, 95% CI 1.46-3.32), and significantly decreased for each 2-fold elevation in circulating PlGF (OR 0.50, 95% CI 0.30-0.82) between 7 and 26 weeks' gestation. Cross-sectional analysis of the angiogenic factors across gestation showed significant differences during the third trimester in women who develop preeclampsia compared with appropriate controls in all high-risk groups. However, when data were examined in relation to the gestational week when preeclampsia was diagnosed only sFlt1 was significantly higher 2 to 5 weeks before the clinical onset of preeclampsia and only in women with previous preeclampsia.


CONCLUSIONS
The pattern of elevated concentrations of sFlt1 and sEng, and low PlGF in high-risk pregnant subjects who develop preeclampsia is similar to that reported in low-risk pregnant women. However, differences in these factors among high-risk women who do and do not develop preeclampsia are modest, and do not appear to be clinically useful predictors in these high-risk pregnant women.
Powers
Robert W
RW
Department of Obstetrics, Gynecology and Women's Health, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America. powersrw@upmc.edu
Jeyabalan
Arun
A
Clifton
Rebecca G
RG
Van Dorsten
Peter
P
Hauth
John C
JC
Klebanoff
Mark A
MA
Lindheimer
Marshall D
MD
Sibai
Baha
B
Landon
Mark
M
Miodovnik
Menachem
M
D000328:Adult; D043925:Angiogenesis Inducing Agents / Q000097:blood; D015703:Antigens, CD / Q000097:blood*; D000071063:Endoglin; D005260:Female; D006801:Humans; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000097:blood* / Q000175:diagnosis; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000097:blood*; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000097:blood*; D011956:Receptors, Cell Surface / Q000097:blood*
D043925:Angiogenesis Inducing Agents; D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D011956:Receptors, Cell Surface; D000072483:Placenta Growth Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor