Preeclampsia is a leading cause of pregnancy-related morbidity and mortality in the United States. In the past 30 years, a large amount of research has been performed to investigate the pathogenesis and pathophysiology of preeclampsia, ways to treat preeclampsia, markers that can be used to predict

A critical review of early-onset and late-onset preeclampsia.

The sFlt-1/PlGF ratio in different types of hypertensive pregnancy disorders and its prognostic potential in preeclamptic patients.

This study prospectively investigates the contribution of pregnancy complications and other reproductive age risk factors on the risk of subsequent cardiovascular disease death. Participants were 14 403 women in the Child Health and Development Studies pregnancy cohort drawn from the Kaiser Permanente Health Plan in California. Only women with nonmissing parity and no previously diagnosed heart conditions were included. A total of 481 had observed preeclampsia, and 266 died from cardiovascular disease. The median age at enrollment was 26 years, and the median follow-up time was 37 years. Cardiovascular disease death was determined by linkage with the California Department of Vital Statistics. Observed preeclampsia was independently associated with cardiovascular disease death (mutually adjusted hazard ratio: 2.14 [95% CI: 1.29 to 3.57]). The risk of subsequent cardiovascular disease death was notably higher among women with onset of preeclampsia by 34 weeks of gestation (hazard ratio: 9.54 [95% CI: 4.50 to 20.26]). At 30 years of follow-up and a median age of 56 years, the cumulative cardiovascular disease death survival for women with early preeclampsia was 85.9% compared with 98.3% for women with late preeclampsia and 99.3% for women without preeclampsia. Women with preeclampsia had an increased risk of cardiovascular disease death later in life, independent of other measured risk factors. These findings reinforce previously reported recommendations that a history of preeclampsia should be used to target women at risk for cardiovascular disease. Additionally, women with preeclampsia earlier in pregnancy may be particularly at risk for cardiovascular disease death and could be targeted for early and intensive screening and intervention.

Preeclampsia and cardiovascular disease death: prospective evidence from the child health and development studies cohort.

The success of pregnancy is a result of countless ongoing interactions between the placenta and the maternal immune and cardiovascular systems. Pre-eclampsia is a serious pregnancy complication that arises from multiple potential aberrations in these systems. The pathophysiology of pre-eclampsia is established in the first trimester of pregnancy, when a range of deficiencies in placentation affect the key process of spiral artery remodelling. As pregnancy progresses to the third trimester, inadequate spiral artery remodelling along with multiple haemodynamic, placental and maternal factors converge to activate the maternal immune and cardiovascular systems, events which may in part result from increased shedding of placental debris. As we understand more about the pathophysiology of pre-eclampsia, it is becoming clear that the development of early- and late-onset pre-eclampsia, as well as intrauterine growth restriction (IUGR), does not necessarily arise from the same underlying pathology.

Pre-eclampsia: fitting together the placental, immune and cardiovascular pieces†

Preeclampsia is a complex disorder which affects an estimated 5% of all pregnancies worldwide. It is diagnosed by hypertension in the presence of proteinuria after the 20th week of pregnancy and is a prominent cause of maternal morbidity and mortality. As delivery is currently the only known treatment, preeclampsia is also a leading cause of preterm delivery. Preeclampsia is associated with maternal vascular dysfunction, leading to serious cardiovascular risk both during and following pregnancy. Endothelial dysfunction, resulting in increased peripheral resistance, is an integral part of the maternal syndrome. While the cause of preeclampsia remains unknown, placental ischemia resulting from aberrant placentation is a fundamental characteristic of the disorder. Poor placentation is believed to stimulate the release of a number of factors including pro- and antiangiogenic factors and inflammatory activators into the maternal systemic circulation. These factors are critical mediators of vascular function and impact the endothelium in distinctive ways, including enhanced endothelial oxidative stress. The mechanisms of action and the consequences on the maternal vasculature will be discussed in this review.

Vascular Dysfunction in Preeclampsia

Objective

This study investigated whether the antiangiogenic factors' concentrations differ according to the clinical manifestations of preeclampsia.



Methods

This study included 62 preeclampsia and compared the soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin (sEng), and placental growth factor (PlGF) concentrations among patients with different clinical manifestations of preeclampsia. We also compared the patients with preeclampsia to 62 controls matched by age, gestational age, and parity after 20 weeks of gestation.



Results

The sEng concentrations were significantly elevated in early-onset than in late-onset preeclampsia (105.4 ± 37.9 vs 66.3 ± 36.0 ng/mL, p = 0.0008). Moreover, the sEng levels were also higher in severe preeclampsia compared to mild (42.5 ± 31.0 vs 79.2 ± 38.6 ng/mL, p = 0.0013) and in the small for gestational age (SGA) group compared to the group without SGA (68.3 ± 39.3 vs 85.7 ± 38.2 ng/mL, p = 0.0273). The sFlt-1 levels, however, did not reveal significant difference according to the onset-time, severity, and presence of SGA. The antiangiogenic factors' concentrations were not related with the degree of hypertension or proteinuria.



Conclusion

Altered antiangiogenic factors might be involved in the pathogenesis of preeclampsia with synergistic, but different roles. Especially, sEng may be more related with early and severe preeclampsia. Copyright © 2009 John Wiley & Sons, Ltd.

The relationship of the level of circulating antiangiogenic factors to the clinical manifestations of preeclampsia.

Preeclampsia (PE), a pregnancy-specific syndrome of hypertension, proteinuria, and other systemic disturbances, is a state of widespread endothelial dysfunction secondary to defective placentation. Morphologically, the current data displayed degenerative and apoptotic changes in the mitochondria and villous trophoblasts of preeclamptic placenta. To reveal the superimposing alterations in placental proteins that might explain the pathophysiology of PE, we performed 2-DE MALDI-TOF MS/MS proteomics analysis of differentially expressed placental proteins with placenta from eight normal and eight preeclamptic pregnancies. The identified proteins were confirmed by Western blot analysis. We also performed morphologic evaluation of preeclamptic placentas under both electron and light microscopy. The results disclosed the marked overexpression of chaperonin 60, GST, VDAC, ERp29, and cathepsin D in PE. These proteomics findings clearly suggest the possible cellular battle against mitochondria-originated oxidative stress during PE that either end up with recovery or apoptosis. These results provide a better understanding of proteomic alterations and may help in clarification of stress-related changes in preeclamptic placentas.

Dae Shim Lee

Papers

The relationship of the level of circulating antiangiogenic factors to the clinical manifestations of preeclampsia.

Toward a better understanding of preeclampsia: Comparative proteomic analysis of preeclamptic placentas.