Pre-Eclampsia: Clinical Manifestations and Molecular Mechanisms

Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
Nephron Clinical Practice (Impact Factor: 1.4). 02/2007; 106(2):c72-81. DOI: 10.1159/000101801
Source: PubMed


Preeclampsia affects 3-5% of pregnancies and can have a significant impact on health for both mother and fetus. Risk factors include maternal co-morbidities such as obesity and chronic hypertension, paternal factors, and genetic factors. New hypertension and proteinuria during the second half of pregnancy are key diagnostic criteria, but the clinical features and associated prognostic implications are somewhat heterogeneous and may reflect different mechanisms of disease. Renal dysfunction and proteinuria correspond to the pathologic finding of glomerular endotheliosis, and generally resolve after cure of preeclampsia through fetal and placenta delivery. The molecular mechanisms behind this disease are being discovered and refined. The initial etiologic agents are currently unknown. Pathologic studies show abnormal development of an ischemic placenta with a high-resistance vasculature, which cannot deliver an adequate blood supply to the fetoplacental unit. Endothelial dysfunction plays a central role in the pathogenesis of the maternal syndrome. Dysfunctional endothelial cells produce altered quantities of vasoactive mediators, which lead to a tip in the balance towards vasoconstriction. An imbalance in circulating angiogenic factors is emerging as a prominent mechanism that mediates the endothelial dysfunction and the clinical signs and symptoms of preeclampsia. Soluble fms-like tyrosine kinase 1 (sFlt1), an endogenous anti-angiogenic factor that is a potent vascular endothelial growth factor (VEGF) antagonist, is highly elevated in preeclampsia. VEGF is not only important in angiogenesis, but also in maintaining endothelial health including the formation of endothelial fenestrae (a hallmark of the glomerular vascular endothelium). sFlt1 overexpression in animals induces glomerular endotheliosis with the loss of endothelial fenestrae that resembles the renal histological lesions of preeclampsia. More severe forms of preeclampsia, including the HELLP syndrome, may be explained by a concomitant elevation in both sFlt1 and soluble endoglin, another anti-angiogenic factor. Unraveling of the molecular mechanisms behind preeclampsia may help to expand our armamentarium to treat patients in a more directed fashion, as current management consists of supportive care and expedited delivery. Finally, long-term outcomes of women with preeclampsia include a significantly increased risk for hypertension and cardiovascular disease, including mortality, which may warrant more aggressive screening and treatment in this population.

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    • "The clinical manifestation varies since PE is associated with several risk factors (obesity, molar pregnancy, hypercoagulation, formation of clots, diabetes mellitus). The prevalence of PE increases up to 66% if there is already an existing chronic kidney disease (Baumwell and Karumanchi 2007). "
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    ABSTRACT: Pre-eclampsia is a serious pathological state affecting 5-10% of pregnant women. Currently, it is diagnosed in the second half of pregnancy, particularly after the 20th week. Symptoms mostly correspond to the changes of blood vessels and kidneys. The severity of pre-eclampsia is proportional to symptomatic manifestations, thus the more symptoms present, the higher is of pre-eclampsia development. Although there are several studies dealing with pre-eclampsia pathology, the complete etiology is still unknown. In this review paper, several theories are presented and discussed.
    Full-text · Article · Oct 2014 · Brazilian Archives of Biology and Technology
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    • "Regarding the age and parity, based on world literature, PE is more often developed at young primiparas and older multiparas; actually it has a bimodal probability [9] [10]. Our study, which includes 300 normotensive and 100 pregnancies with developed PE during the pregnancy, conculded that PE is most commonly developed in primiparas. "
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    ABSTRACT: We studied 300 normotensive and 100 PE pregnancies divided into two subgroups: mild (n = 67) and severe (n = 33) PE. This research has included only single pregnancies and the following parameters: maternal age, parity, previous pregnancy history and interval between pregnancies. The study is based on 400 pregnancies with a mean age of 27.65±5.04 years. The significant difference in the frequency of categories and age groups was tested with a method of multivariate analysis for proportion. The difference was not statistically significant P>0.05, which clearly shows that the groups are a priori similar and comparable. Our study shows that PE is most commonly developed in primiparas (P<0.05). The difference was at the level P<0.001. Among women with no history of PE, the median interbirth interval was 4.24 years between the previous and actual pregnancy. Among women with mild PE the median interbirth interval was 5.96 and in group with severe PE was 8.08 years. Multiparous women who are pregnant 5, especially 10 years or more after their previous pregnancy are as likely to have preeclampsia as nulliparous women.
    Full-text · Article · May 2014
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    • "Worldwide pre-eclampsia (PE) is the first cause of maternal mortality, intrauterine growth retardation (IUGR), and fetal prematurity [1,2]. PE affects 5-10% of pregnancies and is clinically manifested after 20 weeks of gestation (GW) [3,4]. The etiology of PE is still unknown, although an excessive maternal systemic inflammatory response and an imbalance between circulating angiogenic and anti-angiogenic factors have been described [5,6]. "
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    ABSTRACT: Worldwide preeclampsia (PE) is the leading cause of maternal death and affects 5 to 8% of pregnant women. PE is characterized by elevated blood pressure and proteinuria. Doppler Ultrasound (US) evaluation has been considered a useful method for prediction of PE; however, there is no complete data about the most frequently altered US parameters in the pathology. The aim of this study was to evaluate the uterine, umbilical, and the middle cerebral arteries using Doppler US parameters [resistance index (RI), pulsatility index (PI), notch (N), systolic peak (SP) and their combinations] in pregnant women, in order to make a global evaluation of hemodynamic repercussion caused by the established PE. A total of 102 pregnant Mexican women (65 PE women and 37 normotensive women) were recruited in a cases and controls study. Blood velocity waveforms from uterine, umbilical, and middle cerebral arteries, in pregnancies from 24 to 37 weeks of gestation were recorded by trans-abdominal examination with a Toshiba Ultrasound Power Vision 6000 SSA-370A, with a 3.5 MHz convex transducer. Abnormal general Doppler US profile showed a positive association with PE [odds ratio (OR) = 2.93, 95% confidence interval (CI) = 1.2 - 7.3, P = 0.021)], and a specificity and predictive positive value of 89.2% and 88.6%, respectively. Other parameters like N presence, RI and PI of umbilical artery, as well as the PI of middle cerebral artery, showed differences between groups (P values < 0.05). General Doppler US result, as well as N from uterine vessel, RI from umbilical artery, and PI from umbilical and middle cerebral arteries in their individual form, may be considered as tools to determine hemodynamic repercussion caused by PE.
    Full-text · Article · Nov 2013 · BMC Research Notes
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