Accuracy of angiogenic biomarkers at ⩽20weeks' gestation in predicting the risk of pre-eclampsia: A WHO multicentre study

Pregnancy Hypertens. 2015 Oct;5(4):330-8. doi: 10.1016/j.preghy.2015.09.004. Epub 2015 Sep 21.


Objective: To assess the accuracy of angiogenic biomarkers to predict pre-eclampsia.

Design: Prospective multicentre study. From 2006 to 2009, 5121 pregnant women with risk factors for pre-eclampsia (nulliparity, diabetes, previous pre-eclampsia, chronic hypertension) from Argentina, Colombia, Peru, India, Italy, Kenya, Switzerland and Thailand had their serum tested for sFlt-1, PlGF and sEng levels and their urine for PlGF levels at ⩽20, 23-27 and 32-35weeks' gestation (index tests, results blinded from carers). Women were monitored for signs of pre-eclampsia, diagnosed by systolic blood pressure ⩾140mmHg and/or diastolic blood pressure ⩾90mmHg, and proteinuria (protein/creatinine ratio ⩾0.3, protein ⩾1g/l, or one dipstick measurement ⩾2+) appearing after 20weeks' gestation. Early pre-eclampsia was defined when these signs appeared ⩽34weeks' gestation.

Main outcome measure: Pre-eclampsia.

Results: Pre-eclampsia was diagnosed in 198 of 5121 women tested (3.9%) of whom 47 (0.9%) developed it early. The median maternal serum concentrations of index tests were significantly altered in women who subsequently developed pre-eclampsia than in those who did not. However, the area under receiver operating characteristics curve at ⩽20weeks' gestation were closer to 0.5 than to 1.0 for all biomarkers both for predicting any pre-eclampsia or at ⩽34weeks' gestation. The corresponding sensitivity, specificity and likelihood ratios were poor. Multivariable models combining sEng with clinical features slightly improved the prediction capability.

Conclusions: Angiogenic biomarkers in first half of pregnancy do not perform well enough in predicting the later development of pre-eclampsia.

Keywords: Angiogenic biomarkers; Pre-eclampsia; Screening.

Publication types

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

MeSH terms

  • Adult
  • Angiogenic Proteins / blood*
  • Argentina
  • Biomarkers / blood
  • Biomarkers / urine
  • Colombia
  • Female
  • Humans
  • India
  • Italy
  • Kenya
  • Peru
  • Placenta Growth Factor
  • Pre-Eclampsia / blood*
  • Pre-Eclampsia / diagnosis*
  • Pre-Eclampsia / urine
  • Predictive Value of Tests
  • Pregnancy
  • Pregnancy Proteins / blood
  • Pregnancy Proteins / urine
  • Pregnancy Trimester, First / blood
  • Pregnancy Trimester, Second / blood
  • Prospective Studies
  • Sensitivity and Specificity
  • Switzerland
  • Thailand
  • Vascular Endothelial Growth Factor Receptor-1 / blood
  • World Health Organization


  • Angiogenic Proteins
  • Biomarkers
  • PGF protein, human
  • Pregnancy Proteins
  • Placenta Growth Factor
  • Vascular Endothelial Growth Factor Receptor-1