Pre-eclampsia: pathophysiology and clinical implications

Burton, Graham J.; Redman, Christopher W.G.; Roberts, James M.; Moffett, Ashley

doi:10.1136/bmj.l2381

Cited by 764 publications

(797 citation statements)

References 196 publications

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“…The pathophysiology of preeclampsia is complex and remains still under investigation. It is hypothesized that poor trophoblast invasion and deficient spiral artery remodeling lead to placental ischemia‐reperfusion injury 4 and the release of various angiogenic, 5 oxidative, 6 and inflammatory 7 mediators into maternal circulation, promoting generalized endothelial dysfunction, increased vascular reactivity, and activation of the coagulation cascade 8 . Risk stratification is essential in order to identify the subpopulation of pregnant women that would benefit from preventive measures early in the course of gestation, especially the administration of aspirin 9 .…”

Section: Introductionmentioning

confidence: 99%

The prognostic role of serum uric acid levels in preeclampsia: A meta‐analysis

Bellos

Pergialiotis

Loutradis

et al. 2020

J of Clinical Hypertension

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This meta-analysis aims to compare serum uric acid levels among preeclamptic and healthy pregnant women across the various trimesters and provide a summary of the effect size of this biomarker in predicting adverse pregnancy outcomes. MEDLINE, Scopus, CENTRAL, Clinicaltrials.gov, and Google Scholar databases were systematically searched from inception. Observational studies were held eligible if they reported serum uric acid among preeclamptic and healthy pregnant women. Metaanalysis was conducted regarding uric acid concentration, diagnostic accuracy, and association with perinatal outcomes. The credibility of evidence was appraised using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. The analysis included 196 studies, comprising 39 540 women.Preeclampsia was associated with significantly elevated uric acid levels during the 1st (mean difference [MD]: 0.21 mg/dL, 95% confidence intervals [CI]: 0.06-0.35) trimester, 2nd (MD: 1.41 mg/dL, 95% CI: 0.78-2.05) trimester, and 3rd (MD: 2.26 mg/dL, 95% CI: 2.12-2.40) trimester. Higher uric acid was estimated for severe preeclampsia, eclampsia, and hemolysis, elevated liver enzymes, low platelet syndrome. The sensitivity for adverse perinatal outcome prediction ranged from 67.3% to 82.7% and the specificity from 47.7% to 70.7%. In conclusion, it is suggested that serum uric acid levels are increased in preeclampsia and can be used to predict disease severity and pregnancy complications. Future prospective studies should verify these outcomes, assess the optimal cutoffs, and incorporate uric acid to combined predicting models. S U PP O RTI N G I N FO R M ATI O NAdditional supporting information may be found online in the Supporting Information section. How to cite this article: Bellos I, Pergialiotis V, Loutradis D, Daskalakis G. The prognostic role of serum uric acid levels in preeclampsia: A meta-analysis. J Clin Hypertens. 2020;22: 826-834. https://doi.

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Section: Introductionmentioning

confidence: 99%

The prognostic role of serum uric acid levels in preeclampsia: A meta‐analysis

Bellos

Pergialiotis

Loutradis

et al. 2020

J of Clinical Hypertension

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“…Recent studies have shown that sFlt-1 enhances the sensitivity of endothelial cells to pro-inflammatory cytokines rather than having a pro-inflammatory effect itself. The subsequent lack of available PIGF and VEGF results in lower endogenous production of prostacyclin (PGI2) and nitric oxide (NO) and consequently leads to the vasoconstriction of placental arteries, which is crucial for the development of preeclampsia [20].…”

Section: Pathogenesis Of Preeclampsiamentioning

confidence: 99%

Hydroxychloroquine as a Preventive and Therapeutic Option in Preeclampsia – a Literature Review

Deharde

Klockenbusch

Schmitz

et al. 2020

Geburtshilfe Frauenheilkd

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Preeclampsia is one of the most feared complications of pregnancy and puerperium and represents a serious threat to mother and child. In addition, a history of preeclampsia increases the risk of future cardiovascular events. New diagnostic and therapeutic approaches are needed. New therapeutic options are currently being discussed, one of which is the administration of hydroxychloroquine. It is an antimalarial drug which is also used to treat rheumatological disease and its use in pregnancy is considered safe. A reduced incidence of preeclampsia in patients with selected rheumatological disorders after administration of hydroxychloroquine has already been shown; however, the case numbers are very low. Neither the full pathogenesis of preeclampsia nor the exact modes of action of hydroxychloroquine have been completely elucidated, but there are several common features which make hydroxychloroquine a promising option for the prevention and treatment of preeclampsia. Further research, especially prospective, randomized controlled trials, is needed to prove its efficacy. This review discusses the pathogenesis of preeclampsia and gives an overview of new options for its prevention and treatment, including the administration of hydroxychloroquine in pregnancy.

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“…In addition to widespread endothelial dysfunction, alterations to maternal, placental and fetal metabolism are hallmarks of PE [18]. In this study, we explored third trimester placental creatine metabolism in early-onset PE and gestation-matched normotensive pregnancies.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Early-Onset Pre-Eclampsia on Placental Creatine Metabolism in the Third Trimester

Ellery

Murthi

Gatta

et al. 2020

IJMS

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Creatine is a metabolite important for cellular energy homeostasis as it provides spatio-temporal adenosine triphosphate (ATP) buffering for cells with fluctuating energy demands. Here, we examined whether placental creatine metabolism was altered in cases of early-onset pre-eclampsia (PE), a condition known to cause placental metabolic dysfunction. We studied third trimester human placentae collected between 27–40 weeks’ gestation from women with early-onset PE (n = 20) and gestation-matched normotensive control pregnancies (n = 20). Placental total creatine and creatine precursor guanidinoacetate (GAA) content were measured. mRNA expression of the creatine synthesizing enzymes arginine:glycine aminotransferase (GATM) and guanidinoacetate methyltransferase (GAMT), the creatine transporter (SLC6A8), and the creatine kinases (mitochondrial CKMT1A & cytosolic BBCK) was assessed. Placental protein levels of arginine:glycine aminotransferase (AGAT), GAMT, CKMT1A and BBCK were also determined. Key findings; total creatine content of PE placentae was 38% higher than controls (p < 0.01). mRNA expression of GATM (p < 0.001), GAMT (p < 0.001), SLC6A8 (p = 0.021) and BBCK (p < 0.001) was also elevated in PE placentae. No differences in GAA content, nor protein levels of AGAT, GAMT, BBCK or CKMT1A were observed between cohorts. Advancing gestation and birth weight were associated with a down-regulation in placental GATM mRNA expression, and a reduction in GAA content, in control placentae. These relationships were absent in PE cases. Our results suggest PE placentae may have an ongoing reliance on the creatine kinase circuit for maintenance of cellular energetics with increased total creatine content and transcriptional changes to creatine synthesizing enzymes and the creatine transporter. Understanding the functional consequences of these changes warrants further investigation.

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Pre-eclampsia: pathophysiology and clinical implications

Cited by 764 publications

References 196 publications

The prognostic role of serum uric acid levels in preeclampsia: A meta‐analysis

The prognostic role of serum uric acid levels in preeclampsia: A meta‐analysis

Hydroxychloroquine as a Preventive and Therapeutic Option in Preeclampsia – a Literature Review

The Effects of Early-Onset Pre-Eclampsia on Placental Creatine Metabolism in the Third Trimester

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