Preeclampsia: Creating a urinary screening test
After thromboembolic disease, preeclampsia is the second most common cause of maternal death in the US. Although the condition can't be prevented, early identification of women at risk for developing it would enable obstetricians to improve clinical outcomes for both mother and child. With the recent identification of angiogenic factors present in high concentrations in the urine of women at risk, a urinary screening test may soon be a reality.
Key Points
Preeclampsia complicates from 6% to 8% of all pregnancies.2,3 It's the second most common cause of maternal mortality in the United States (after thromboembolic disease), accounting for from 12% to 18% of all pregnancy-related maternal deaths-around 70 deaths per year in the US and an estimated 50,000 deaths per year worldwide.3-5 It has also been linked to high perinatal mortality and morbidity rates, due primarily to iatrogenic prematurity.6
Deciphering the causes
HOW PREECLAMPSIA DEVELOPS. Although there's still no single theory that can account for all of the findings in preeclampsia, the pathologic hallmark appears to be complete or partial failure of the second wave of trophoblast invasion from 16 to 20 weeks' gestation.12-14 In normal pregnancies, this trophoblast invasion is responsible for destruction of the muscularis layer of the spiral arterioles and establishment of the definitive uteroplacental circulation.
As a result of abnormally shallow trophoblast invasion, the spiral arterioles of preeclamptic placentae retain their thick muscularis layer and are unable to dilate sufficiently in the second half of pregnancy to meet the increasing metabolic demands of the growing fetus and placenta. This leads to relative placental ischemia and, for want of a better term, "placental dysfunction" that causes the release of an endogenous placental toxin that damages the vasculature throughout the maternal circulatory system. Because of this placental toxin, this condition was previously referred to as "preeclamptic toxemia." Although preeclampsia can only be diagnosed after 20 weeks' gestation with evidence of new-onset gestational proteinuric hypertension, it is clear that the blueprint for its development is laid down early in pregnancy.15
IDENTIFYING THE TOXINS. We have yet to definitively identify the placental toxemic factor(s) responsible for the widespread endothelial damage that categorizes preeclampsia, although recent attention has focused on circulating angiogenic factors. Data from mouse studies, from the study of human trophoblast cells in vitro, and from measurements of angiogenic factors in the serum and urine of pregnant women suggest that preeclampsia may result from excessive levels of circulating antiangiogenic factors. These toxins may also be responsible for subsequent neonatal injury, including acute and chronic lung injury.16-20
