The use of angiogenic factors in discriminating preeclampsia: are they ready for prime time?
OBJECTIVE
We sought to evaluate the association between soluble fms-like tyrosine kinase 1 (sFlt1) and endoglin (ENG) and preeclampsia in an urban population, to develop a discriminatory model, and evaluate the association of these biomarkers with small for gestational age (SGA).


METHODS
Cases are prospectively identified with preeclampsia. Controls are term patients without preeclampsia. Commercially available ELISAs were used to measure levels of sFlt1, ENG, and placental growth factor (PlGF). Log-transformed levels were compared and multivariable logistic regression analyses were performed to control for confounders. Receiver operating characteristic curves were developed.


RESULTS
In cases (n=86) compared to controls (n=288), sFlt1 (p=0.24) levels were no different. However, ENG levels were higher (p<0.001), and PlGF levels were lower (p<0.001). Further, levels of sFlt1 had poor discriminatory ability between cases and controls [AUC=0.56, (0.48–0.63)]. The best model to discriminate between groups included clinical risk factors, ENG, and PlGF [AUC=0.89, (0.85–0.92)].


CONCLUSIONS
Unlike recent reports, this study suggests that sFlt1 may have limited diagnostic utility in predicting preeclampsia, especially term disease.
Srinivas
Sindhu K
SK
Department of Obstetrics and Gynecology, University of Pennsylvania Health System, Philadelphia, PA 19104, USA. ssrinivas@obgyn.upenn.edu
Larkin
Jacob
J
Sammel
Mary D
MD
Appleby
Dina
D
Bastek
Jamie
J
Andrela
Christina M
CM
Ofori
Ella
E
Elovitz
Michal A
MA
D000328:Adult; D042501:Angiogenic Proteins / Q000032:analysis* / Q000097:blood; D015703:Antigens, CD / Q000032:analysis / Q000097:blood; D016022:Case-Control Studies; D003937:Diagnosis, Differential; D000071063:Endoglin; D005260:Female; D005317:Fetal Growth Retardation / Q000097:blood / Q000175:diagnosis / Q000209:etiology; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis / Q000097:blood; D011225:Pre-Eclampsia / Q000097:blood / Q000175:diagnosis*; D011247:Pregnancy; D012372:ROC Curve; D011956:Receptors, Cell Surface / Q000032:analysis / Q000097:blood; D012680:Sensitivity and Specificity; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000032:analysis / Q000097:blood; D055815:Young Adult
D042501:Angiogenic Proteins; D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D008565:Membrane Proteins; C098069:PIGF protein, human; D011956:Receptors, Cell Surface; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1