Plasma sFlt-1/PlGF ratio of 11.5 multiples of median predicts preeclampsia with severe features within two weeks of testing

Angiogenic imbalances, characterized by an excess of antiangiogenic factors (soluble fms-like tyrosine kinase 1 [sFlt-1]) and reduced angiogenic factors (VEGF and placental growth factor [PlGF]), contribute to the mechanisms of disease in preeclampsia. The ratio of sFlt-1 to PlGF has been used as a biomarker for preeclampsia, but cut-off values may vary with gestational age and assay platform. To compare multiples of the median (MoM) of maternal plasma sFlt-1/PlGF ratio, sFlt-1, PlGF, and conventional clinical and laboratory values to predict preeclampsia with severe features. We conducted a cohort study across 18 U.S. centers involving hospitalized hypertensive individuals between 23-35 weeks' gestation. Receiver operating characteristic curve (ROC) analyses of maternal plasma biomarkers, highest systolic or diastolic blood pressures, and laboratory values at enrollment were performed for the prediction of preeclampsia with severe features. Their areas under the curve (AUC) were compared, and quasi-Poisson regression models were fitted to estimate relative risks. The primary outcome was preeclampsia with severe features within two weeks of enrollment. Secondary outcomes were a composite of severe adverse maternal outcomes (elevated liver enzymes, low platelets count, placental abruption, eclampsia, disseminated intravascular coagulation, and pulmonary edema) and a composite of severe adverse perinatal outcomes (birthweight