Abstract

Introduction The soluble fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio is CE-mark approved for short-term prediction of preeclampsia in women with clinical suspicion of the syndrome (gestational age 24weeks+0d–36weeks+6d). Objectives We evaluated sFlt-1/PlGF as a predictive marker for early-onset preeclampsia in women at high risk of preeclampsia. Methods STEPS (prospective/multicenter) included pregnant women with preeclampsia risk factors (including history of IUGR/preeclampsia/eclampsia/HELLP syndrome, pre-gestational diabetes, antiphospholipid antibodies, and abnormal uterine artery Doppler). Primary objective: to show that sFlt-1/PlGF was predictive of early-onset preeclampsia ( ® sFlt-1 and PlGF assays, cobas electrochemiluminescence platform, Roche Diagnostics, Germany); bilateral uterine artery Doppler; blood pressure/proteinuria/preeclampsia status assessment. Results were compared by ANOVA/Dunnet and Wilcoxon signed-rank test. For prediction of early-onset preeclampsia, the area under the curve (AUC) of receiver operating characteristic curves (ROC) was calculated. Singleton pregnancies are reported. Results 819 subjects were enrolled. Of 442 women with singleton pregnancies 42 (9.5%) developed preeclampsia (14 early-onset/28 late-onset). The mean (SD) sFlt-1/PlGF ratio at 20, 24, and 28 weeks was: 7.86 (8.61), 5.9 (12.38) and 4.59 (5.65) for subjects who did not develop preeclampsia (control); 53.15 (61.79), 69.25 (105.53) and 180.37 (241.83) for early-onset preeclampsia; and 7.81 (4.45), 5.09 (3.34) and 13.39 (34.52) for late-onset preeclampsia. Compared with early-onset preeclampsia the sFlt-1/PlGF ratio was significantly lower for control, chronic hypertension, transient hypertension, and late-onset preeclampsia (Figure). Prediction of early-onset preeclampsia (ROC AUC [95% CI]) was best for sFlt-1/PlGF plus clinical data (0.94 [0.90–0.98], 0.94 [0.89–1.0], 0.94 [0.86–1.0], at 20, 24 and 28 weeks) vs sFlt-1/PlGF alone (0.78 [0.62–0.95], 0.82 [0.65–0.98], 0.86 [0.72–1.0]) or Doppler alone (0.71 [0.56–0.86], 0.73 [0.54–0.91], 0.87 [0.74–1.0]). Conclusion The sFlt-1/PlGF ratio can improve prediction of early-onset preeclampsia for women at high risk of preeclampsia.

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