Angiogenic Markers Predict Pregnancy Complications and Prolongation in Preeclampsia: Continuous Versus Cutoff Values

Hypertension. 2017 Nov;70(5):1025-1033. doi: 10.1161/HYPERTENSIONAHA.117.09913. Epub 2017 Aug 28.

Abstract

To assess the incremental value of a single determination of the serum levels of sFlt-1 (soluble Fms-like tyrosine kinase 1) and PlGF (placental growth factor) or their ratio, without using cutoff values, for the prediction of maternal and fetal/neonatal complications and pregnancy prolongation, 620 women with suspected/confirmed preeclampsia, aged 18 to 48 years, were included in a prospective, multicenter, observational cohort study. Women had singleton pregnancies and a median pregnancy duration of 34 (range, 20-41) weeks. Complications occurred in 118 women and 248 fetuses. The median duration between admission and delivery was 12 days. To predict prolongation, PlGF showed the highest incremental value (R2=0.72) on top of traditional predictors (gestational age at inclusion, diastolic blood pressure, proteinuria, creatinine, uric acid, alanine transaminase, lactate dehydrogenase, and platelets) compared with R2=0.53 for the traditional predictors only. sFlt-1 showed the highest value to discriminate women with and without maternal complications (C-index=0.83 versus 0.72 for the traditional predictors only), and the sFlt-1/PlGF ratio showed the highest value to discriminate fetal/neonatal complications (C-index=0.86 versus 0.78 for the traditional predictors only). Applying previously suggested cutoff values for the sFlt-1/PlGF ratio yielded lower incremental values than applying continuous values. In conclusion, sFlt-1 and PlGF are strong and independent predictors for days until delivery along with maternal and fetal/neonatal complications on top of the traditional criteria. Their use as continuous variables (instead of applying cutoff values for different gestational ages) should now be tested in a prospective manner, making use of an algorithm calculating the risk of an individual woman with suspected/confirmed preeclampsia to develop complications.

Keywords: algorithms; fetus; gestational age; preeclampsia; pregnancy.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Gestational Age
  • Humans
  • Middle Aged
  • Netherlands / epidemiology
  • Placenta Growth Factor / blood*
  • Pre-Eclampsia* / blood
  • Pre-Eclampsia* / diagnosis
  • Pre-Eclampsia* / epidemiology
  • Predictive Value of Tests
  • Pregnancy
  • Prognosis
  • Reproducibility of Results
  • Risk Factors
  • Vascular Endothelial Growth Factor Receptor-1 / blood*

Substances

  • Placenta Growth Factor
  • Vascular Endothelial Growth Factor Receptor-1