Vasoactive agents for the prediction of early- and late-onset preeclampsia in a high-risk cohort

BACKGROUND To evaluate the soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and sFlt-1/PlGF ratio for the prediction of early- and late-onset preeclampsia in a high-risk cohort. METHODS We studied serial serum samples collected prospectively at 12+0-14+0, 18+0-20+0, and 26+0-28+0 weeks+days of gestation in 6 women who developed early-onset preeclampsia (before 34 weeks of gestation) and in 21 women who developed late-onset preeclampsia (after 34 weeks of gestation) with automated ElecSys 2010 immunoanalyzer (Roche Diagnostics, Germany). Twenty-six high-risk women and 53 women without risk factors with normal pregnancies served as controls. RESULTS Serum PlGF concentrations were lower at 18+0 to 20+0, and 26+0 to 28+0 weeks of gestation in women who developed early-onset preeclampsia compared to women who developed late-onset preeclampsia and to controls (p<0.05 for all comparisons). At 18+0 to 20+0 weeks of gestation area under the receiver-operating characteristic curve (AUC) for serum PlGF was 99.8% (p=0.0007, 95% CI 99.0-100.0). At 26+0 to 28+0 weeks of gestation serum sFlt-1/PlGF ratio explicitly detects those women who developed early-onset preeclampsia (AUC 100.0%, p=0.0007, 95% CI 100-100). Amongst women with late-onset preeclampsia, those who developed severe form of the disease (N=8) had significantly higher serum sFlt-1 concentrations at all three timepoints (p=0.004, p=0.006, and p=0.003, respectively) compared to women with non-severe form (N=13). CONCLUSIONS Low serum PlGF concentration predicts early-onset preeclampsia from the second trimester and elevated serum sFlt-1/PlGF ratio from 26 to 28 weeks of gestation. Elevated serum sFlt-1 concentration in the first trimester in women who later develop late-onset, severe preeclampsia may suggest different etiology compared to the late-onset non-severe form of the disease.