Preclampsia

Preeclampsia
Author: Kee-Hak Lim, MD, Associate Professor, Department of Obstetrics and Gynecology, Harvard Medical School; Consulting Staff, Harvard Medical Faculty Physicians and Beth Israel Deaconess Medical Center
Coauthor(s): Guy Steinberg, MD, MPH, MSc, Fellow in Maternal-Fetal Medicine, Beth Israel Deaconess Medical Center/Harvard Medical School
Contributor Information and DisclosuresUpdated: Aug 31, 2010
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Background
Preeclampsia is a pregnancy-specific syndromecharacterized by new-onset hypertension and proteinuria, occurring usually after 20 weeks' gestation. Although the etiology remains unknown, placental hypoperfusion and diffuse endothelial cell injury are considered be the central pathologic events. Preeclampsia is classified into mild and severe types and, in its extreme, may lead to liver and renal failure, disseminated intravascular coagulopathy, andcentral nervous system abnormalities, including seizures. Because the only cure is delivery, preeclampsia is associated with high maternal and neonatal mortality and morbidity. In the United States, preeclampsia is believed to be responsible for 15% of premature deliveries1 and 17.6% of maternal deaths.2,3Worldwide, preeclampsia and eclampsia are estimated to be responsible for approximately 14% ofmaternal deaths per year (50,000-75,000).4 

Despite its impact on maternal and child health, efforts to predict and prevent the disease have been disappointing. Numerous strategies (low-dose aspirin, calcium, and vitamin C and E supplementation) have been shown to be of little benefit. Because our understanding of the pathogenesis of this disease is incomplete, these preventive strategies wereproposed based on pathogenetic hypotheses that did not withstand the test of time. Recently, a number of investigators demonstrated and confirmed that an imbalance in angiogenic molecules play a major role in the pathogenesis of preeclampsia, raising the possibility that these molecules may be targeted for preventive measures and possible palliative therapy.-------------------------------------------------
Pathophysiology
The general consensus is that preeclampsia is an endothelial cell disorder resulting in mild-to-severe microangiopathy of target organs such as brain, liver, kidney, and placenta.5  While hypertension may be the most common presenting symptom, it should not be viewed as the initial pathogenetic process. Evidence of other organ involvement before hypertension becomesfulminant is not uncommon. Several circulating markers of endothelial cell injury have been shown to be elevated in women who develop preeclampsia before they became symptomatic. These include endothelin, cellular fibronectin, plasminogen activator inhibitor-1, and altered prostacyclin/thromboxane profile.6 Evidence to date suggests that oxidative stress; circulatory maladaptation; inflammation; andhumoral, mineral, and metabolic abnormalities may all contribute to endothelial dysfunction and pathogenesis of preeclampsia.
 
Many investigators believe that the placenta is the trigger for endothelial cell injury.7  Evidence suggests that hypoperfused placentas produce various factors that are capable of injuring endothelial cells. Recent data suggest that circulating factors that interferewith the action of vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) play a major role in maternal manifestation of the disorder (see Angiogenic Factors in Preeclampsia).

Placental hypoperfusion or ischemia in preeclampsia has many causes. Preexisting vascular disorders such as hypertension and connective tissue disorders can result in poor placental circulation. In...