First‐trimester maternal serum PP‐13, PAPP‐A and second‐trimester uterine artery Doppler pulsatility index as markers of pre‐eclampsia

Spencer, Kevin; Cowans, Nicholas J.; Chefetz, Ilana; Tal, J.; Meiri, Hamutal

doi:10.1002/uog.3876

Cited by 201 publications

(170 citation statements)

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“…[7][8][9][10][11][12][13][14][15] However, less remarkable predictive properties have been reported in recent studies, with some describing a potential role of PP13 levels for predicting preeclampsia or small for gestational age (SGA) in combination with other biomarkers. [9,12,15] Variation in study design, population characteristics, numbers of cases and reporting of the diagnostic accuracy of PP13, have made it difficult to interpret the clinical significance of these results.…”

Section: Introductionmentioning

confidence: 99%

First trimester screening of maternal placental protein 13 for predicting preeclampsia and small for gestational age: In-house study and systematic review

et al. 2012

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Objective: To describe normative levels of PP13 in first-trimester of pregnancy and determine the accuracy of PP13 in predicting preeclampsia and small for gestational age (SGA) infants.Methods: We measured PP13 in archived first trimester serum samples from an unselected maternal cohort of 2,989 women. Associations of PP13 levels and diagnostic accuracy in predicting adverse pregnancy outcomes were assessed using multivariate logistic regression models. Due to inadequate number of cases we then conducted a systematic review involving structured search of electronic databases and subsequent meta-analysis of predictive accuracy using data from similar studies.Results: Overall, 2,678 women were included in the in-house study with 71 (2.7%) preeclampsia cases, 5 (0.2%) early-onset preeclampsia (≤34 weeks) cases; and 191 (7.1%) and 41 (1.5%) infants SGA<10 th and <3 rd centile. Median (IQR) normative level of PP13 in unaffected pregnancies was 53.5 (37.7-71.8) pg/ml. The area under the receiver operating characteristic curve (AUC) for multivariate models was 0.72 (95%CI 0.66-0.78) for preeclampsia; 0.82 (95%CI 0.63-0.99) for early-onset preeclampsia; 0.73 (95%CI 0.69-0.77) for SGA<10 th centile; and 0.83 (95%CI 0.78-0.88) for SGA<3 rd centile. Eight studies were included in the systematic review, normative levels of PP13 was assessed in four studies but these were variable; and meta-analysis was performed on seven studies. Sensitivity rates of PP13 based on 5% fixed false positive rates were 24%, 45% and 26% for preeclampsia, for early-onset preeclampsia and SGA, respectively.Conclusions: First-trimester PP13, in combination with maternal characteristics and other serum biomarkers was inadequate for screening purposes and predicting women at risk.

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Section: Introductionmentioning

confidence: 99%

First trimester screening of maternal placental protein 13 for predicting preeclampsia and small for gestational age: In-house study and systematic review

et al. 2012

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“…Certainly, early uterine artery Doppler measurement does seem to have less discrimination than that done at 22 to 24 weeks (Martin et al, 2001) although there is little or no correlation between reduced levels of PAPP-A in the first trimester and uterine artery Doppler either in the first trimester (Prefumo et al, 2006) or second trimester (Spencer et al, 2005b). The early identification of women at increased risk of developing pre-eclampsia by a combination of low PAPP-A alone or in combination with other markers such as inhibin, activin or PP13 (Ong et al, 2004;Spencer et al, 2006bSpencer et al, , 2007cNicolaides et al, 2006), along side uterine artery Doppler measurement and maternal factors (Yu et al, 2005) may allow increased surveillance or early possible therapeutic interventions with low dose aspirin in an attempt to arrest the disease progression. Further studies are required to establish the clinical value of these approaches.…”

Section: Discussionmentioning

confidence: 99%

“…Some of the pre-eclamptic cases included in this study were part of our previous studies (Spencer et al, 2005b(Spencer et al, , 2007c. The association between PAPP-A and the incidence of pre-eclampsia was assessed by comparing the relative incidence at a number of MoM cut-offs and at various centile cut-offs.…”

Section: Methodsmentioning

confidence: 99%

Low levels of maternal serum PAPP‐A in the first trimester and the risk of pre‐eclampsia

Spencer

Cowans²,

Nicolaides³

2007

Prenatal Diagnosis

183

113

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Background Low levels of pregnancy associated plasma protein-A (PAPP-A) have been previously shown to be associated with pregnancies that subsequently develop pre-eclampsia. The objective of this study was to establish the relative risk for pre-eclampsia at various PAPP-A levels as an aid to counselling and follow up of pregnancies.Methods Maternal serum PAPP-A and free ß-human chorionic gonadotropin (ß-hCG) levels at 11 to 13 weeks of gestation from 224 singleton pregnancies that subsequently developed pre-eclampsia were compared to those from 47 770 normal singleton pregnancies resulting in live births after 37 weeks with birth weight greater than or equal to the 10th centile of normal for gestation. In all cases, the measured PAPP-A and free ß-hCG levels were expressed as multiple of the median (MoM). The association between metabolite levels and the incidence of pre-eclampsia was assessed by comparing the relative incidence at a number of MoM cut-offs and at various centiles. At various marker levels, the likelihood ratio for pre-eclampsia was also calculated. ResultsIn the pre-eclampsia group the median PAPP-A MoM was significantly reduced (0.772 MoM, p < 0.0001) whilst the median free β-hCG MoM was not different from controls (0.981 MoM, p = 0.26). With decreasing levels of PAPP-A, the likelihood ratio for pre-eclampsia increased. At the 5th centile of normal (PAPP-A MoM 0.415) the odds ratio was increased 4-fold and at this cut-off 15% of cases of pre-eclampsia would be identified. ConclusionsThe graphical presentation of a likelihood ratio curve for pre-eclampsia at any PAPP-A MoM level is likely to be useful in counselling women with low levels of PAPP-A and a normal karyotype. Use of low levels of PAPP-A for selecting women for further follow-up with uterine artery Doppler may further improve the clinical discrimination.

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“…PAPP-A and PP13 serum levels were significantly lower in the first and second trimesters in women who developed preeclampsia [68] . First-trimester PAPP-A provided a prediction for preeclamspia when combined with uterine artery pulsatility measured by Doppler velocimetry [69] . Activin A and inhibin A During the first trimester of pregnancy, the foeto-placental unit is the main source of circulating activin A and inhibin A. Activin A enhances Follicle-stimulating hormone (FSH) biosynthesis and secretion and is involved in the control of trophoblast cell differentiation in the first trimester.…”

Section: Placental Protein 13mentioning

confidence: 99%

Preeclampsia from a renal point of view: Insides into disease models, biomarkers and therapy

Müller-Deile

Schiffer

2014

WJN

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Proteinuria is a frequently detected symptom, found in 20% of pregnancies. A common reason for proteinuria in pregnancy is preeclampsia. To diagnose preeclampsia clinically and to get new insights into the pathophysiology of the disease it is at first essential to be familiar with conditions in normal pregnancy. Animal models and biomarkers can help to learn more about disease conditions and to find new treatment strategies. In this article we review the changes in kidney function during normal pregnancy and the differential diagnosis of proteinuria in pregnancy. We summarize different pathophysiological theories of preeclampsia with a special focus on the renal facets of the disease. We describe the current animal models and give a broad overview of different biomarkers that were reported to predict preeclampsia or have a prognostic value in preeclampsia cases. We end with a summary of treatment options for preeclampsia related symptoms including the use of plasmapheresis as a rescue therapy for so far refractory preeclampsia. Most of these novel biomarkers for preeclampsia are not yet implemented in clinical use. Therefore, we recommend using proteinuria (measured by UPC ratio) as a screening parameter for preeclampsia. Delivery is the only curative treatment for preeclampsia. In early preeclampsia the primary therapy goal is to prolong pregnancy until a state were the child has an acceptable chance of survival after delivery.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Preeclampsia; Pregnancy; Proteinuria; Biomarkers; Treatment Core tip: This review summarises different pathophysiological theories of preeclampsia with a special focus on the renal facets of the disease. In this context current animal models are presented. The reader gets a broad overview about different biomarkers for preeclampsia. Furthermore, the article discusses treatment options for preeclampsia related symptoms including the use of plasmapheresis as a rescue therapy for so far refractory preeclampsia.Müller-Deile J, Schiffer M. Preeclampsia from a renal point of view: Insides into disease models, biomarkers and therapy. World

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First‐trimester maternal serum PP‐13, PAPP‐A and second‐trimester uterine artery Doppler pulsatility index as markers of pre‐eclampsia

Abstract: Objective To evaluate whether measurement of maternal serum placental

Cited by 201 publications

References 52 publications

First trimester screening of maternal placental protein 13 for predicting preeclampsia and small for gestational age: In-house study and systematic review

First trimester screening of maternal placental protein 13 for predicting preeclampsia and small for gestational age: In-house study and systematic review

Low levels of maternal serum PAPP‐A in the first trimester and the risk of pre‐eclampsia

Preeclampsia from a renal point of view: Insides into disease models, biomarkers and therapy

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