Addition of N-terminal pro-B natriuretic peptide to soluble fms-like tyrosine kinase-1/placental growth factor ratio > 38 improves prediction of pre-eclampsia requiring delivery within 1 week: a longitudinal cohort study

Ultrasound Obstet Gynecol. 2018 Jun;51(6):758-767. doi: 10.1002/uog.19040.

Abstract

Objective: Short-term prediction of pre-eclampsia (PE) using the soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio is characterized by frequent false-positive results. As such, no treatment can be recommended to test-positive patients and multiple measurements are often required. The aim of this study was to evaluate the effectiveness of N-terminal pro-B natriuretic peptide (NT-proBNP), uric acid and the sFlt-1/PlGF ratio for prediction of delivery with PE within 1 week in singleton pregnancies with suspected PE and sFlt-1/PlGF ratio > 38.

Methods: This was a longitudinal prospective cohort study of singleton pregnancies presenting at 24 + 0 to 36 + 6 weeks of gestation with clinically suspected PE and sFlt-1/PlGF ratio > 38, enrolled between January 2015 and June 2017. Multiple samples per patient were allowed but were restricted to one sample per gestational week. From 495 enrolled patients, 270 blood samples from 134 patients were ultimately analyzed. By using generalized estimating equations (GEE), the best-fit model was selected for prediction of delivery with PE within 1 week. The predictive value of this model was then assessed using area under the paired-ROC curve (AUC) analysis.

Results: The best-fit model included the sFlt-1/PlGF ratio, NT-proBNP and the gestational week at the time of the measurement. This combined model was compared with the GEE model based on the sFlt-1/PlGF ratio and the gestational week at the time of the measurement (reduced model). The AUC for the combined model was 0.845 (95% CI, 0.787-0.896), which was significantly greater (P = 0.011) than that of the reduced model (0.786 (95% CI, 0.722-0.844)).

Conclusion: The addition of NT-proBNP assessment improves the short-term prediction of delivery as a result of PE compared with sFlt-1/PlGF ratio alone, when the sFlt-1/PlGF ratio is > 38. This finding should be considered in future research on the assessment of short-term risk of delivery as a result of PE. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Keywords: NT-proBNP; generalized estimating equations; longitudinal study; pre-eclampsia rule-in; sFlt-1/PlGF ratio.

Publication types

  • Evaluation Study

MeSH terms

  • Adult
  • Biomarkers / blood*
  • Cohort Studies
  • Delivery, Obstetric
  • Female
  • Gestational Age
  • Humans
  • Longitudinal Studies
  • Natriuretic Peptide, Brain / blood*
  • Peptide Fragments / blood*
  • Placenta Growth Factor / blood
  • Pre-Eclampsia / blood
  • Pre-Eclampsia / diagnosis*
  • Predictive Value of Tests
  • Pregnancy
  • Prenatal Diagnosis*
  • Vascular Endothelial Growth Factor Receptor-1 / blood

Substances

  • Biomarkers
  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Placenta Growth Factor
  • Vascular Endothelial Growth Factor Receptor-1