Elucidating the causes of preeclampsia

Increased blood levels of soluble endoglin and ratios of soluble fms-like tyrosine kinase 1 (sFlt1): placental growth factor (PlGF) trumpet the onset of preeclampsia, according to the results of a nested case–control study of healthy nulliparous women within the Calcium for Preeclampsia Prevention Trial.

Richard J. Levine, MD, MPH, and colleagues found that circulating soluble endoglin levels increased markedly 2 to 3 months prior to the onset of preeclampsia. Mean serum levels in women with preeclampsia prior to 37 weeks' gestation were more than five times higher than in controls (46.4 ng/mL vs. 9.8 ng/mL; P<0.001). In women with the disease at term, levels were two to three times higher than in controls (31.0 ng/mL vs. 13.3 ng/mL; P<0.001). At 17 through 20 weeks' gestation, levels in women who later developed preterm preeclampsia were almost double those in controls (10.2 ng/mL vs. 5.8 ng/mL; P<0.001). And at 25 through 28 weeks' gestation, mean serum levels in women who later developed term preeclampsia were 8.5 ng/mL vs. 5.9 ng/mL in controls (P<0.001).

An increased mean serum soluble endoglin was usually accompanied by an increase in the ratio of the antiangiogenic protein, sFlt1, to PlGF. Women with the highest levels of endoglin and the highest ratio of sFlt1:PlGF were at greatest risk for the disease.

Commentary by Charles J. Lockwood, MD, Anita O'Keefe Young Professor and Chair, Dept. of Ob/Gyn, Yale University School of Medicine, New Haven, Conn.:

In this recent analysis, researchers found that endoglin, an antiangiogenic protein, which is a novel placenta-derived soluble TGF-β coreceptor, appears to also be involved in the pathogenesis of preeclampsia. This recent finding seems to be yet another important step toward development of an accurate diagnostic test for preeclampsia. This publication also lends support to the previous findings that the ratio between sFlt1/PlGF is superior to random serum protein measurements, and the addition of endoglin may further improve diagnosis. Yet, as Dr. Levine has cautioned, attempts to develop a diagnostic test or drug treatment are still years away.

Buhimschi CS, Norwitz ER, Funai E, Lockwood CJ, et al. Urinary angiogenic factors cluster hypertensive disorders and identify women with severe preeclampsia. Am J Obstet Gynecol. 2005;192:734-741.