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Endocrine, vol. 19, no. 1, 113–125, October 2002 0969–711X/02/19:113–125/$20.00 © 2002 by Humana Press Inc. All rights of any nature whatsoever reserved.

Pathophysiology and Maternal Biologic Markers of Preeclampsia
Jacques Massé,1,2 Yves Giguère,1,2 Abdelaziz Kharfi,1 Joël Girouard,1 and Jean-Claude Forest 1,2

Perinatology Research Unit, 2Center for the Development, the Evaluation andthe Rational Implantation of New Diagnostic Technologies (CEDERINDT), Hôpital Saint-François d’Assise Research Center, CHUQ, Quebec City, Quebec, Canada

Preeclampsia—increased blood pressure and proteinuria appearing after the twentieth week of pregnancy —is a major cause of materal and neonatal morbidity, leading to iatrogenic prematurity. Several lines of evidence suggest that the disorder isowing to diminished invasion of spiral arteries by trophoblastic cells, followed by reduced perfusion of the fetoplacental unit and oxidative stress. These alterations, in the presence of maternal predisposition, lead to endothelial dysfunction and occurrence of the clinical syndrome of preeclampsia (multisystemic lesions). Although the pathophysiology of preeclampsia is still unknown, progresshas been made during the past 10 yr, and the early identification of at-risk women with the use of biochemical; ultrasonographic; and, more recently, genetic susceptibility markers has been the subject of intense research. In the present review, markers of maternal predisposition, placental implantation, oxidative stress, vasomotor regulation, and endothelial dysfunction are investigated ascandidate markers in the early prediction of preeclampsia. Unfortunately, at the present time, no marker has been proven to have a clinically useful predictive performance in the general pregnant population, and, therefore, more research in that area is warranted. Key Words: Preeclampsia; screening; endothelium; insulin resistance; oxidation; placenta.

Pregnancy is characterized byadaptive physiologic changes reflected in variations in the homeostasis of blood volume, blood pressure, and immune response, among others. Diseases presenting during pregnancy are associated with various alterations in these physiologic responses. The various mediators involved in these biologic mechanisms, and in particular those detectable in maternal blood, either directly or by way of more stablemetabolites are logical candidates

for the early detection of pregnancy pathologies, in the hope of applying targeted preventive measures. To be clinically useful, the candidate marker must be measurable in noninvasively obtained specimens (usually maternal blood or urine). The technology necessary for its measurement must be widely available and relatively cheap to be applicable for thegeneral pregnant population. Abnormal levels must be present before the development of clinically detectable disease (to still be considered a screening test and to allow the implementation of preventive measures before full installation of the pathologic manisfestations). In populations with low incidence of the disease, the marker must be relatively specific to maintain an acceptable positivepredictive value (in particular if invasive, potentially harmful, or costly preventive measures are envisaged after a positive screening test). Preeclampsia is a disease limited to the female gender during pregnancy. Its major manifestation is hypertension, as well as variable involvement of various organs (kidney, liver, brain), generally appearing after the twentieth week of pregnancy (1–3). Thedisease’s prevalence using current classifications (3,4) varies from 3 to 8% in developed countries (5–9). It is a leading cause of maternal mortality in developed countries and increases perinatal mortality fivefold (10). The only definitive treatment of preeclampsia (11) is delivery of the infant; thus, this disease is a major cause of iatrogenic prematurity. It is estimated that 15% of preterm...
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