Accuracy of angiogenic biomarkers at ⩽20weeks' 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 32-35weeks' 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.

The relationship of angiogenic factors to maternal and neonatal manifestations of early-onset and late-onset preeclampsia.

OBJECTIVE: An imbalance between angiogenic and antiangiogenic factors has been implicated in the pathogenesis and severity of preeclampsia. In this study, we evaluated serum levels of an angiogenic factor and an antiangiogenic factor - placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1), respectively - in pregnant women with preeclampsia, as well as evaluating the impact of those factors on maternal and fetal outcomes. METHOD: We studied 44 pregnant women diagnosed with preeclampsia and admitted to an intensive care unit (ICU). The preeclampsia was classified (by weeks of gestation at delivery) as early-onset (<34 weeks) or late-onset (≥34 weeks). We analyzed serum PlGF and sFlt-1, as well as urinary PlGF at admission to the ICU. RESULTS: In the early-onset preeclampsia group, the sFlt-1/PlGF ratio was higher, as was serum sFlt-1, whereas serum PlGF was lower. Serum sFlt-1 and the sFlt-1/PlGF ratio correlated positively with proteinuria and length of maternal hospital stay and correlated negatively with birth weight. The sFlt-1/PlGF ratio correlated positively with length of newborn stay in the neonatal ICU. CONCLUSION: Angiogenic imbalance is more pronounced in patients with early-onset preeclampsia and correlates with worse clinical outcomes, especially for the neonates.