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

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 32-35 weeks' gestation (index tests, results blinded from carers). Women were monitored for signs of pre-eclampsia, diagnosed by systolic blood pressure >= 140 mmHg and/or diastolic blood pressure >= 90 mmHg, and proteinuria (protein/creatinine ratio >= 0.3, protein >= 1 g/l, or one dipstick measurement >= 2+) appearing after 20 weeks' gestation. Early pre-eclampsia was defined when these signs appeared <= 34 weeks' 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 <= 20 weeks' gestation were closer to 0.5 than to 1.0 for all biomarkers both for predicting any pre-eclampsia or at <= 34 weeks' 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. (C) 2015 Published by Elsevier B.V. on behalf of International Society for the Study of Hypertension in Pregnancy.