A simple urine test that measures placental growth factor (PlGF) at mid-gestation may someday predict which pregnant women are at high risk of developing preeclampsia, setting the stage for the prevention of its progression and life-threatening complications. At least that's the implication of a nested case–control study reported recently in JAMA.
The investigation, part of the Calcium for Preeclampsia Prevention trial of healthy nulliparous women from five United States university medical centers, found that a reduced urinary PlGF, a proangiogenic protein, is strongly associated with subsequent development of preeclampsia.
Mean urinary PlGF levels of women in the study who developed the hypertensive disorder were 32 pg/mL, compared with 234 pg/mL among controls with fetuses of similar gestational age (P<0.001). The difference was apparent as early as the 25th week of gestation and became more pronounced by the 29th through the 36th week.
The study builds upon a previous finding that soluble fms-like tyrosine kinase (sFlt-1) circulates in large quantities in the blood of women with preeclampsia, binding to PlGF and VEGF (vascular endothelial growth factor) and preventing their use by the blood vessel cells that require them.
Levine RJ, Thadhani R, Qian C, et al. Urinary placental growth factor and risk of preeclampsia. JAMA. 2005;293:77-85.
Commentary by Errol Norwitz, MD, PhD Yale University School of Medicine:In recent years, several tests have been proposed to identify subgroups of women at increased risk of developing preeclampsia, including urinary placental growth factor (PlGF) measurements. The data presented in Levine et al's study, although an important step in the right direction, are still too preliminary to be incorporated into clinical practice. To begin with, the analysis was done on samples stored at –70°C for over 10 years, and proteins are known to degrade with time. Another limitation of the study was that, although mean urinary PlGF levels were statistically different, there was substantial overlap between individual samples obtained from women who subsequently developed preeclampsia and normotensive controls. It's therefore unlikely that urinary PlGF levels alone will be able to accurately identify women at risk of developing preeclampsia.
Should other researchers confirm the link between urinary PlGF and preeclampsia, however, it's possible that a urine screening test for preeclampsia may be available in 4 to 5 years. But the most important question is: Will such a screening test change perinatal outcome? There is currently no reliable preventative treatment for preeclampsia other than delivery of the fetus and placenta, and there is no intervention that has been shown to delay progression of the disease. While an accurate screening test would undoubtedly be a step in the right direction, how will our patients react when we tell them that they are likely to develop a serious life-threatening disorder of pregnancy within the next few weeks, but there is nothing we can do to prevent or treat it? We clinicians had better have a good answer hidden away somewhere in our white coats!
Sibai BM. Prevention of preeclampsia: a big disappointment. Am J Obstet Gynecol. 1998;179:1275-1278.
Norwitz ER, Robinson JN, Repke JT. Prevention of preeclampsia: is it possible? Clin Obstet Gynecol. 1999;42:436-454.