A more accurate prediction to rule in and rule out pre-eclampsia using the sFlt-1/PlGF ratio and NT-proBNP as biomarkers

Lafuente-Ganuza, Paula; Lequerica-Fernández, Paloma; Carretero, Francisco; Escudero, Ana I; Martínez‐Morillo, Eduardo; Sabrià, Enric; Herraı̀z, Ignacio; Galindo, Alberto; López, Ana Pérez; Martínez-Triguero, María L.; Álvarez, Francisco V.

doi:10.1515/cclm-2019-0939

Cited by 15 publications

(15 citation statements)

References 37 publications

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“…In contrast to copeptin and MR‐proANP, another cardiovascular biomarker, N‐terminal pro‐B natriuretic peptide (NT‐proBNP), has shown incremental value in predicting short‐term delivery due to PE 19 when added to sFlt‐1/PlGF ratio > 38. Similarly, a recent study demonstrated that adding NT‐proBNP > 174 pg/mL to an sFlt‐1/PlGF ratio > 45 increases significantly the positive predictive value of sFlt‐1/PlGF ratio 20 . In a study by Verlohren et al 21 ,.…”

Section: Discussionmentioning

confidence: 92%

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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Section: Discussionmentioning

confidence: 92%

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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“…Studies have reported elevated levels of NT-pro BNP in established pre-eclampsia with or without ventricular failure [ 14 , 16 , 37 ], but the benefit of using NT-pro BNP for predicting pre-eclampsia is uncertain [ 38 , 39 ]. A recent study reported a better predictive value for pre-eclampsia when adding NT-pro BNP to the existing biomarkers (soluble FMS-like tyrosine kinase 1 and placental growth factor) [ 40 ]. However, the NT-pro BNP cut-off used (174 pg/mL) falls directly between the 2 reference limits defined in our study, and we propose that our findings in support of trimester-specific RIs may improve this further.…”

Section: Discussionmentioning

confidence: 99%

Pregnancy-specific Reference Intervals for BNP and NT-pro BNP—Changes in Natriuretic Peptides Related to Pregnancy

Dockree

Brook

Shine

et al. 2021

Journal of the Endocrine Society

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Background Cardiac disease is the leading cause of maternal mortality in the UK, so accurate cardiovascular diagnoses in pregnancy are essential. BNP (B-type natriuretic peptide) and NT-pro BNP (N-terminal-pro BNP) are useful clinical tools for investigating suspected peripartum cardiomyopathy but, as the pregnancy-specific reference intervals are undefined, it is uncertain how they should be interpreted in pregnant women. Methods Longitudinal study of 260 healthy pregnant women, with sampling in each trimester to define 95% reference intervals. Results The upper reference limit for NT-pro BNP was 200 pg/mL in the first and second trimesters, and 150 pg/mL in the third. Levels were significantly reduced in overweight women in the third trimester (p=0.0001), which supports the partitioning of reference intervals by BMI. The upper limit for BNP was 50 pg/mL, with no detectable trimester-related differences. Whilst other biomarkers (haemoglobin and platelets) fell throughout pregnancy, both natriuretic peptides were initially elevated before falling by the third trimester, suggesting that the observed changes in natriuretic peptides are driven by dynamic interplay between cardiac strain and progressive haemodilution. NT-pro BNP in the first trimester was inversely associated with neonatal birthweight at term (p=0.011). Conclusions Cardiac biomarkers have an important role for investigating suspected disease in high-risk pregnant women, but a robust assessment of the levels expected in healthy pregnant women is an essential prerequisite to their application in clinical practice. This study has defined trimester- and BMI-specific reference intervals for NT-pro BNP and BNP, which may improve how women with suspected cardiovascular disease are investigated in pregnancy.

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“…The MLM to predict PE included six predictors, as previously published [ 22 ]. Briefly, GA at admission, chronic hypertension, and biomarker serum levels (sFlt-1, PlGF, NT-proBNP, uric acid), corrected for GA at sampling, were included.…”

Section: Methodsmentioning

confidence: 99%

“…Neither NT-proBNP nor uric acid individually have been shown to be good predictors for PE [ 21 ], but models combining these biomarkers show promise. Lafuente-Ganuza et al [ 22 ], published in 2020 a predictive machine-learning algorithm for early-onset PE using a combination of the sFlt-1/PlGF ratio, NT-proBNP and uric acid as biomarkers, with apparent better positive predictive values (PPV) than the sFlt-1/PlGF ratio alone. External validation is necessary to determine reproducibility for a prediction model and applicability to different populations.…”

Section: Introductionmentioning

confidence: 99%

Predictive Model for Preeclampsia Combining sFlt-1, PlGF, NT-proBNP, and Uric Acid as Biomarkers

Garrido

Cruz‐Lemini²,

Álvarez³

et al. 2023

JCM

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N-terminal pro-brain natriuretic peptide (NT-proBNP) and uric acid are elevated in pregnancies with preeclampsia (PE). Short-term prediction of PE using angiogenic factors has many false-positive results. Our objective was to validate a machine-learning model (MLM) to predict PE in patients with clinical suspicion, and evaluate if the model performed better than the sFlt-1/PlGF ratio alone. A multicentric cohort study of pregnancies with suspected PE between 24+0 and 36+6 weeks was used. The MLM included six predictors: gestational age, chronic hypertension, sFlt-1, PlGF, NT-proBNP, and uric acid. A total of 936 serum samples from 597 women were included. The PPV of the MLM for PE following 6 weeks was 83.1% (95% CI 78.5–88.2) compared to 72.8% (95% CI 67.4–78.4) for the sFlt-1/PlGF ratio. The specificity of the model was better; 94.9% vs. 91%, respectively. The AUC was significantly improved compared to the ratio alone [0.941 (95% CI 0.926–0.956) vs. 0.901 (95% CI 0.880–0.921), p < 0.05]. For prediction of preterm PE within 1 week, the AUC of the MLM was 0.954 (95% CI 0.937–0.968); significantly greater than the ratio alone [0.914 (95% CI 0.890–0.934), p < 0.01]. To conclude, an MLM combining the sFlt-1/PlGF ratio, NT-proBNP, and uric acid performs better to predict preterm PE compared to the sFlt-1/PlGF ratio alone, potentially increasing clinical precision.

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A more accurate prediction to rule in and rule out pre-eclampsia using the sFlt-1/PlGF ratio and NT-proBNP as biomarkers

Cited by 15 publications

References 37 publications

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

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

Pregnancy-specific Reference Intervals for BNP and NT-pro BNP—Changes in Natriuretic Peptides Related to Pregnancy

Predictive Model for Preeclampsia Combining sFlt-1, PlGF, NT-proBNP, and Uric Acid as Biomarkers

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