Early Prediction of Preeclampsia

Poon, Liona C.; Nicolaides, Kypros H.

doi:10.1155/2014/297397

Cited by 216 publications

(175 citation statements)

References 106 publications

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“…Early-onset preeclampsia can be predicted with reasonable accuracy by the second trimester with multiparameter screening, providing an opportunity for the initiation of preventative therapies before the onset of clinical symptoms. [31][32][33] In this capacity, LMWH could potentially avert serious maternal vascular dysfunction during pregnancy, leading to improved clinical outcomes. Importantly, LMWH has demonstrated a good safety profile in pregnant women with no obvious maternal or fetal side effects or major bleeding episodes.…”

Section: Perspectivesmentioning

confidence: 99%

Low Molecular Weight Heparin Improves Endothelial Function in Pregnant Women at High Risk of Preeclampsia

et al. 2017

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Preeclampsia is a hypertensive disorder of pregnancy characterized by new-onset hypertension with evidence of organ injury, affecting 2% to 8% of all pregnancies worldwide. 1 The majority of women with preeclampsia present clinically near term with favorable maternal and infant outcomes; however, a subset of women develop severe disease characterized by the need for preterm delivery typically before 34 weeks of gestation because of end-organ injury, severe hypertension, or intrauterine growth restriction.2 Women with severe preeclampsia demonstrate significant cardiovascular impairment during pregnancy and the immediate postpartum period and a higher risk of cardiovascular disease later in life.3-7 Given the significant shortand long-term maternal cardiovascular effects of preeclampsia, elucidating its pathogenesis has been of much interest in recent years. However, as yet, there is no agreement concerning the most effective pharmacological therapy for the prevention of preeclampsia in screen-positive women beyond aspirin, with clinical symptoms typically only resolving on delivery. Low molecular weight heparin (LMWH) has been evaluated for the prevention of various placenta-mediated pregnancy complications, including severe preeclampsia and recurrent miscarriage. Multiple trials and systematic reviews have concluded that LMWH reduces the incidence of recurrent severe preeclampsia in high-risk women, as well as perinatal mortality, preterm birth, and infant birth weight <10th percentile for gestational age, whereas other studies have found no treatment effect.9,10 Because the majority of previous trials have consisted of clinical end points, the mechanism of action of LMWH for the possible prevention of severe preeclampsia is currently unknown. Evidence suggests that observed beneficial effects do not result from heparin's anticoagulant actions within the placenta.11,12 An alternative hypothesis is that LMWH exerts vascular actions in the maternal compartment that reverse the systemic vascular dysfunction characteristic of preeclampsia. Previous trials in patients with coronary artery disease have determined that LMWH demonstrates beneficial endothelial effects, possibly through increased bioavailability of NO. 13,14The objective of the current study was to investigate the endothelial effects of LMWH in pregnant women at high risk of preeclampsia. We first compared baseline cardiovascular Abstract-Low molecular weight heparin (LMWH) has been investigated for the prevention of severe preeclampsia, although the mechanisms of action are unknown. The objective of this study was to investigate the cardiovascular effects of LMWH in pregnant women at high risk of preeclampsia. Pregnant women at high risk of preeclampsia (n=25) and low-risk pregnant controls (n=20) at 22 to 26 weeks' gestation underwent baseline cardiovascular assessments. Highrisk women were then randomized to LMWH or saline placebo (30 mg IV bolus and 1 mg/kg subcutaneous dose). Cardiovascular function was assessed 1 and 3 hours post randomization. T...

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Section: Perspectivesmentioning

confidence: 99%

Low Molecular Weight Heparin Improves Endothelial Function in Pregnant Women at High Risk of Preeclampsia

et al. 2017

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“…The delay between the initial (presumably immune rejection/poor implantation) event and the activation of other immune/angiogenic mecha-nisms to elicit the clinical presentation of preeclampsia implies the existence of another unidentified mechanism to link these processes across the first trimester. That uterine artery dysfunction appears already in the first trimester (14) supports the concept that a vascular modulator may be involved in this "missing link" mechanism.…”

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confidence: 58%

Vasopressin: the missing link for preeclampsia?

Sandgren¹,

Scroggins²,

Santillan

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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eclampsia is a devastating cardiovascular disorder of late pregnancy, affecting 5-7% of all pregnancies and claiming the lives of 76,000 mothers and 500,000 children each year. Various lines of evidence support a "tissue rejection" type reaction toward the placenta as the primary initiating event in the development of preeclampsia, followed by a complex interplay among immune, vascular, renal, and angiogenic mechanisms that have been implicated in the pathogenesis of preeclampsia beginning around the end of the first trimester. Critically, it remains unclear what mechanism links the initiating event and these pathogenic mechanisms. We and others have now demonstrated an early and sustained increase in maternal plasma concentrations of copeptin, a protein by-product of arginine vasopressin (AVP) synthesis and release, during preeclampsia. Furthermore, chronic infusion of AVP during pregnancy is sufficient to phenocopy essentially all maternal and fetal symptoms of preeclampsia in mice. As various groups have demonstrated interactions between AVP and immune, renal, and vascular systems in the nonpregnant state, elevations of this hormone are therefore positioned both in time (early pregnancy) and function to contribute to preeclampsia. We therefore posit that AVP represents a missing mechanistic link between initiating events and established midpregnancy dysfunctions that cause preeclampsia. preeclampsia; pregnancy; vasopressin; copeptin; hypertension PREECLAMPSIA is a disease of pregnancy annually affecting more than 6.5 million pregnancies worldwide characterized by hypertension, multiorgan dysregulation, and maternal-fetal mortality (22). Although the ultimate etiology of preeclampsia is still unknown, the concepts that 1) the fetal-placental unit represents an allogenic, transplanted tissue to the mother, and 2) that preeclampsia is initiated through a rejection-type reaction have been forwarded by leaders in the field based on significant epidemiological and basic science data (13,15,17,21). Dysregulation of the normal maternal immune tolerance to the fetus has been implicated as an initiator, as the immunological changes observed in the placenta of preeclamptic pregnancies is very similar to those observed in rejected organ transplants (13). Complementary studies of immunological tolerance also support these concepts. In humans, a 30% decreased risk of preeclampsia is observed with couples having a second child compared with those who change paternity in the second pregnancy (7,24). Mouse models demonstrate that the disruption of immune tolerance mechanisms is sufficient to replicate human preeclampsia phenotypes (8,19). Resulting immune rejection reactions are thought to lead to poor placental implantation, poor placental perfusion, and, by mechanisms not yet clearly delineated, the clinical symptoms of preeclampsia (15).Numerous factors have been implicated in the midgestational progression of preeclampsia, including cytokines like tumor necrosis factor-␣, anti-angiogenic factors like soluble fms-like tyro...

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“…A variety of algorithms constructed from combinations of clinical risk factors, 14 uterine artery Doppler, 15 and blood biomarkers 16 can predict women at risk of severe PE with reasonable accuracy. 17,18 Despite advances in knowledge regarding the pathophysiology of PE, there has been no parallel progress toward the development of effective pharmacological therapies to prevent the disease in screen-positive women.…”

Section: Current Therapies For the Prevention And Treatment Of Pementioning

confidence: 99%