Maternal serum sFlt-1/PlGF ratio in twin pregnancies with and without pre-eclampsia in comparison with singleton pregnancies.

Abstract

In singleton pregnancies, soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF) and the sFlt-1/PlGF ratio have shown utility as a diagnostic test for pre-eclampsia (PE). The objective of this study was to characterize the maternal serum levels of sFlt-1, PlGF and sFlt-1/PlGF ratio in normal and pre-eclamptic twin pregnancies. In a European multicenter case-control study, 49 women with a twin pregnancy were enrolled, including 31 uneventful and 18 pre-eclamptic pregnancies. sFlt-1 and PlGF were measured and receiver-operating characteristics (ROC) analysis was performed. The median sFlt-1 and PlGF serum concentrations and sFlt-1/PlGF ratio were compared with those of a singleton cohort, matched for gestational age, with PE (n = 54) and with an uncomplicated pregnancy outcome (n = 238). In twin pregnancies with PE, sFlt-1 levels and the sFlt-1/PlGF ratio were increased and PlGF levels were decreased as compared with those of twin gestations with an uneventful pregnancy outcome (20 011.50 ± 2330.35 pg/mL vs 4503.00 ± 2012.05 pg/mL (P ≤ 0.001), 164.22 ± 31.35 vs 13.29 ± 319.64 (P ≤ 0.001), and 138.80 ± 20.04 pg/mL vs 403.00 ± 193.10 pg/mL (P ≤ 0.001), respectively). The sFlt-1/PlGF ratio did not differ between twin pregnancies with PE and singleton pregnancies with PE. In twin pregnancies with an uneventful outcome, sFlt-1 levels and sFlt-1/PlGF ratio were increased, but no differences in PlGF concentration were found when compared with that of singleton controls. ROC analysis determined 53 as an optimal cut-off of the sFlt-1/PlGF ratio for diagnosing PE in twin gestations, yielding a sensitivity of 94.4% and a specificity of 74.2%. The cut-off values established for singleton pregnancies, of 33 and 85, led to sensitivities of 100% and 83.3%, and specificities of 67.7% and 80.6%, when used to detect PE in twin pregnancies. Significant differences in the serum marker levels in singleton vs twin pregnancies were detected. Reference ranges of sFlt-1, PlGF and their ratio in singleton pregnancies are therefore not transferable to twin pregnancies.