Maternal serum copeptin, MR-proANP and procalcitonin levels at 11–13 weeks gestation in the prediction of preeclampsia

Birdir, C; Janssen, Katharina; Stănescu, Anca Daniela; Enekwe, A; Kasimir‐Bauer, Sabine; Gellhaus, Alexandra; Köninger, Angela

doi:10.1007/s00404-015-3745-7

Cited by 21 publications

(17 citation statements)

References 38 publications

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“…Copeptin, a glycosylated polypeptide consisting of the 39 C-terminal amino acids of arginine vasopressin, has been suggested as “a new biomarker that is specific for preeclampsia” (712), and certainly changes during its development (713). However, it turns out that it is also essentially a measure of all kinds of stresses and adverse events (714–719), including those caused by infection (720–729).…”

Section: Proteomic and Similar Biomarkers – Circulating And Placentalmentioning

confidence: 99%

A Dormant Microbial Component in the Development of Preeclampsia

Kell

Kenny

2016

Front. Med.

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Preeclampsia (PE) is a complex, multisystem disorder that remains a leading cause of morbidity and mortality in pregnancy. Four main classes of dysregulation accompany PE and are widely considered to contribute to its severity. These are abnormal trophoblast invasion of the placenta, anti-angiogenic responses, oxidative stress, and inflammation. What is lacking, however, is an explanation of how these themselves are caused. We here develop the unifying idea, and the considerable evidence for it, that the originating cause of PE (and of the four classes of dysregulation) is, in fact, microbial infection, that most such microbes are dormant and hence resist detection by conventional (replication-dependent) microbiology, and that by occasional resuscitation and growth it is they that are responsible for all the observable sequelae, including the continuing, chronic inflammation. In particular, bacterial products such as lipopolysaccharide (LPS), also known as endotoxin, are well known as highly inflammagenic and stimulate an innate (and possibly trained) immune response that exacerbates the inflammation further. The known need of microbes for free iron can explain the iron dysregulation that accompanies PE. We describe the main routes of infection (gut, oral, and urinary tract infection) and the regularly observed presence of microbes in placental and other tissues in PE. Every known proteomic biomarker of “preeclampsia” that we assessed has, in fact, also been shown to be raised in response to infection. An infectious component to PE fulfills the Bradford Hill criteria for ascribing a disease to an environmental cause and suggests a number of treatments, some of which have, in fact, been shown to be successful. PE was classically referred to as endotoxemia or toxemia of pregnancy, and it is ironic that it seems that LPS and other microbial endotoxins really are involved. Overall, the recognition of an infectious component in the etiology of PE mirrors that for ulcers and other diseases that were previously considered to lack one.

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Section: Proteomic and Similar Biomarkers – Circulating And Placentalmentioning

confidence: 99%

A Dormant Microbial Component in the Development of Preeclampsia

Kell

Kenny

2016

Front. Med.

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“…Another study comprising 50 pregnant women with PE, 54 healthy pregnant women and 33 non-pregnant women, concluded that copeptin was a strong predictor for the development of PE in all three trimesters of pregnancy, with areas under the curve (AUC) of 0.90, 0.90 and 0.78, respectively 9 . Conversely, two smaller studies were unable to demonstrate such findings 8,18 . Sugulle et al 6 measured MR-proANP at 24 to 42 weeks' gestation in 77 normotensive and 107 PE pregnancies and found that MR-proANP had an AUC of 0.85 in discriminating between PE pregnancies and normotensive pregnant controls, which was inferior to that of sFlt-1 (AUC, 0.94).…”

Section: Discussionmentioning

confidence: 93%

Copeptin and mid‐regional pro‐atrial natriuretic peptide in women with suspected or confirmed pre‐eclampsia: comparison with sFlt‐1/PlGF ratio

Neuman

Meer

Saleh

et al. 2020

Ultrasound in Obstet & Gyne

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Objectives Arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) may contribute to the pathogenesis of pre‐eclampsia (PE), but their role remains to be elucidated. Our aims were to evaluate the surrogates of AVP and ANP, C‐terminal pro‐AVP (copeptin) and mid‐regional pro‐ANP (MR‐proANP), as biomarkers for the prediction of PE‐related pregnancy complications and whether they are associated with angiogenic markers and/or clinical manifestations of PE. Methods This was a retrospective analysis of a prospective cohort study that enrolled pregnant women with suspected or confirmed PE, between December 2013 and April 2016. From each patient, a blood sample was obtained at study entry and serum levels of copeptin, MR‐proANP, soluble fms‐like tyrosine kinase‐1 (sFlt‐1) and placental growth factor (PlGF) were measured. We evaluated the ability of sFlt‐1, PlGF, sFlt‐1/PlGF ratio, copeptin and MR‐proANP, assessed either alone or combined with traditional predictors (gestational age, parity, diastolic blood pressure and proteinuria), to predict maternal complications and fetal/neonatal complications. Models were compared using concordance statistic (C‐index). Results A total of 526 women were evaluated in the study. Women with confirmed PE displayed elevated serum copeptin and MR‐proANP levels in comparison to those with suspected PE but no hypertensive disease of pregnancy. When combined with traditional predictors, the sFlt‐1/PlGF ratio displayed a higher C‐index than copeptin and MR‐proANP (0.76, 0.63 and 0.67, respectively, vs 0.60 for the traditional predictors alone) for the prediction of maternal complications. Similarly, for the prediction of fetal/neonatal complications, the sFlt‐1/PlGF ratio displayed a higher C‐index than copeptin and MR‐proANP when added to the traditional model (0.83, 0.79 and 0.80, respectively, vs 0.79 for the traditional predictors alone). When subdividing women according to sFlt‐1/PlGF ratio (≥ 85 vs < 85), no differences in copeptin levels were observed, while MR‐proANP level was elevated in women with sFlt‐1/PlGF ratio ≥ 85. Multiple regression analysis revealed that copeptin and MR‐proANP were independent determinants of proteinuria. Conclusions Copeptin and MR‐proANP have limited value in predicting PE‐related complications when compared with the sFlt‐1/PlGF ratio. However, both copeptin and MR‐proANP were associated with proteinuria, with copeptin exerting this effect independently of the sFlt‐1/PlGF ratio. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

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“…A potential pathogenic role of arginine vasopressin in preeclampsia was proposed based on elevated circulating concentrations of copeptin. Most (Zulfikaroglu et al, 2011;Santillan et al, 2014;Yeung et al, 2014;Tuten et al, 2015), but not all (Birdir et al, 2015) groups reported elevated circulating copeptin levels before and/or during the clinical manifestations of the disease. In one study, the increase in copeptin concentrations measured at 16 weeks of gestation was specific for preeclampsia, not being observed in women who developed gestational hypertension (without proteinuria), gestational diabetes mellitus or preterm birth in the absence of preeclampsia (Yeung et al, 2014).…”

Section: Arginine Vasopressin Receptorsmentioning

confidence: 98%

G-Protein-coupled receptors as potential drug candidates in preeclampsia: targeting the relaxin/insulin-like family peptide receptor 1 for treatment and prevention

Conrad

2016

Hum. Reprod. Update

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There is a strong scientific rationale for RXFP1 activation in severe preeclampsia by administration of relaxin, relaxin analogs or small molecule mimetics, in order to mollify the disease pathogenesis for safe prolongation of pregnancy, thus allowing time for more complete fetal maturation, which is a primary therapeutic endpoint in treating the disease. In light of recent data implicating deficient or defective decidualization as a potential etiological factor in preeclampsia and the capacity of relaxin to promote endometrial maturation, the prophylactic application of relaxin to reduce the risk of preeclampsia is a plausible therapeutic approach to consider. Finally, given its pleiotropic and beneficial attributes particularly in the cardiovascular system, relaxin, although traditionally considered as a 'pregnancy' hormone, is likely to prove salutary for several disease indications in the non-pregnant population.

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Maternal serum copeptin, MR-proANP and procalcitonin levels at 11–13 weeks gestation in the prediction of preeclampsia

Abstract: The maternal serum copeptin, MR-proANP and PCT levels are higher in EO-PE and LO-PE patients, but the difference is not significant. Thus, their levels in first trimester are not proven to be effective markers to screen for PE.

Cited by 21 publications

References 38 publications

A Dormant Microbial Component in the Development of Preeclampsia

A Dormant Microbial Component in the Development of Preeclampsia

Copeptin and mid‐regional pro‐atrial natriuretic peptide in women with suspected or confirmed pre‐eclampsia: comparison with sFlt‐1/PlGF ratio

G-Protein-coupled receptors as potential drug candidates in preeclampsia: targeting the relaxin/insulin-like family peptide receptor 1 for treatment and prevention

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