A novel approach to first‐trimester screening for early pre‐eclampsia combining serum PP‐13 and Doppler ultrasound

Nicolaides, Kypros H.; Bindra, Ranjna; Turan, Özhan; Chefetz, Ilana; Sammar, Marei; Meiri, Hamutal; Tal, J.; Cuckle, Howard

doi:10.1002/uog.2686

Cited by 259 publications

(218 citation statements)

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“…One study reported a PP13 median of 66.6 pg/ml for controls, [16] and another presented medians by week of gestation for weeks [11][12][13]; with values of 53.5, 63.1, 65.7 pg/ml, respectively; [19] while a study of nulliparous women reported slightly higher levels of PP-13 (77.3 pg/ml). [17] In comparison, median level of PP13 among controls in the in-house study was 53.5 (IQR; 37.7-71.8) pg/ml for all woman, 54.7 (IQR; 39.8-72.1) pg/ml for nulliparous women and 53.9, 54.0, 52.5 pg/ml for gestational week 11-13, respectively.…”

Section: Systematic Review and Meta-analysismentioning

confidence: 99%

“…[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%

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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: Systematic Review and Meta-analysismentioning

confidence: 99%

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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“…Currently, clinical history, maternal serum biochemistry and uterine artery Doppler sonography before 14 weeks are being investigated. [4][5][6][7] In the second trimester, uterine artery Doppler can claim a detection rate (DR) of only 63.1% for a high (25%) false-positive rate (FPR). 8 First-trimester uterine artery Doppler studies have been shown to have high sensitivity but poor specificity, with a high FPR.…”

Section: Introductionmentioning

confidence: 99%

Pulse wave analysis: a preliminary study of a novel technique for the prediction of pre‐eclampsia

Khalil

Cooper

Harrington

2008

BJOG

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Objective To investigate whether first-trimester arterial pulse wave analysis (PWA) can predict pre-eclampsia.Design This was a prospective screening study.Setting The Homerton University Hospital, a London teaching hospital.Population Two hundred and ten low-risk women with a singleton pregnancy were analysed.Methods Radial artery pulse waveforms were measured between the 11 +0 and 13 +6 weeks of gestation and the aortic waveform derived by applying a generalised transfer function. Augmentation pressure (AP) and augmentation index at heart rate of 75 beats per minute (AIx-75), measures of arterial stiffness, were calculated. The multiple of the gestation-specific median in controls for AP and AIx-75 were calculated. Logistic regression models were developed and their predictive ability assessed using the area under the receiver operator curve.Main outcome measures Prediction of pre-eclampsia by AIx-75.Results Fourteen (6.7%) women developed pre-eclampsia, and 196 remained normotensive. Eight of the 14 women developed pre-eclampsia before 34 weeks of gestation (early-onset pre-eclampsia). For a false-positive rate of 11%, AIx-75 had a detection rate of 79% for all cases of pre-eclampsia and 88% for early-onset pre-eclampsia.Conclusion First-trimester arterial PWA can play a significant role in understanding the pathophysiology of pre-eclampsia and may play a role in early screening.

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“…Recent studies have demonstrated that patients who subsequently developed preeclampsia had lower maternal serum PP13 concentrations in the first trimester than women who had a normal pregnancy outcome [2,6].…”

Section: Mutations In the Lgals13 Gene And Their Impact On The Use Ofmentioning

confidence: 99%

“…Other analytes which appear promising include activin A, inhibin A, PAPP-A, and PP13 [1]. Recent studies have also suggested that it may be valuable to combine the results of biochemical tests with uterine artery Doppler velocimetry in the first and second trimesters [1][2]. This workshop was organized to highlight recent discoveries in the field.…”

Section: Introductionmentioning

confidence: 99%

Prediction of Preeclampsia – A Workshop Report

et al. 2008

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Understanding the mechanisms of disease responsible for the syndrome of preeclampsia as well as early risk assessment is still a major challenge. The concentrations of circulating proteins in maternal blood such as placental growth factor, soluble vascular endothelial growth factor receptor-1 and soluble endoglin are altered weeks before the onset of clinical symptoms of the syndrome. Recently, other proteins in maternal serum, such as activin A, inhibin A, PAPP-A, and PP13 have been suggested to be of value in first trimester risk assessment. Since preeclampsia is a syndrome, it seems unlikely that a single test will predict all forms of preeclampsia. This realization has led to the formulation of a new conceptual framework suggesting that a combination of markers (biochemical and/or biophysical) may be required to conduct comprehensive risk assessment for the syndrome.

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A novel approach to first‐trimester screening for early pre‐eclampsia combining serum PP‐13 and Doppler ultrasound

Abstract: Objective To investigate the value of maternal serum placental protein 13

Cited by 259 publications

References 18 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

Pulse wave analysis: a preliminary study of a novel technique for the prediction of pre‐eclampsia

Prediction of Preeclampsia – A Workshop Report

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