•
•
•
•
The hypertensive syndrome of preeclampsia, a hypertensive disorder which occurs only in pregnancy, is believed to result from a circulating anti-angiogenic state caused by an imbalance of pro- and anti-angiogenic factors in maternal blood. We have recently identified two anti-angiogenic factors which are produced in excess by women who will subsequently develop preeclampsia. One is soluble vascular endothelial growth factor receptor 1 (sVEGFR1) or sFlt1, which binds the pro-angiogenic factors VEGF and placental growth factor (PlGF). The other is a soluble co-receptor designated sX, which blocks the activity of one or more of the pro-angiogenic TGF beta family of proteins. We have demonstrated that both factors are elevated months before the onset of preeclampsia and levels correlate with severity of subsequent disease. High serum levels of sFlt1 and sX, as well as low levels of VEGF and PlGF, indicate high risk for preeclampsia with onset before 37 weeks (preterm preeclampsia). We have also shown that low levels of PlGF in urine are associated with high risk for preterm preeclampsia and have described the potential utility of urinary PlGF concentration as a screening test, especially when abnormal urinary values are followed by measurement of serum concentrations of angiogenic factors.
I expect to begin in FY 2007 a study to develop a prediction model capable of identifying whether a pregnant woman will or will not develop clinical preeclampsia within the next 2 weeks. The study would enroll women at high risk of preeclampsia by virtue of having insulin-dependent diabetes, chronic hypertension, multifetal gestation, or previous preeclampsia. Women would undergo intensive surveillance for preeclampsia, including frequent measurements of blood pressure and urine protein. Our prediction model could include baseline characteristics of the women, blood pressure measurements in clinic, plasma glucose, uterine artery Doppler ultrasonographic measurements of impedance to blood flow at 22-24 weeks of gestation, and angiogenic factor concentrations in blood and urine. We would obtain blood and urine every 2 weeks from 20-36 weeks of gestation to measure angiogenic factor concentrations. The prediction model would be updated every 2 weeks with new information and could incorporate not only angiogenic factor levels, but also rate of change of these levels. The study would enroll 1000 women over 2 years at 4 clinical centers and would have a data center and a central laboratory for angiogenic factor measurements.
A postdoctoral fellow would have a unique opportunity to help develop the study protocol, design data forms, and assist in multiple aspects with conduct of the study. The study will be very similar to conduct of a clinical trial, so experience with this study will be valuable experience and equip the fellow to perform large studies including clinical trials in obstetric populations.
