First trimester screening for pre-term preeclampsia combining placental growth factor and cell-free DNA fetal fraction: development of a preliminary theoretical model

Purpose Develop a preliminary theoretical model of placental growth factor (PlGF), cell-free DNA fetal fraction (FF) and prior risks in pre-term preeclampsia (PE) and unaffected pregnancies. Methods Fitting a bivariate Gaussian marker distribution and maternal prior risk factors to a preliminary series. Marker levels were expressed in multiples of the median (MoMs) using fitted regression equations. Unaffected parameters were obtained from the preliminary series; PE parameters from the literature or making reasonable assumptions. Results 2149 women were tested at 9–14 weeks; pregnancy outcome was not available. Log-linear MoMing equations, after log (PlGF) or square-root (FF) transformation, fitted the data well. Medians in 42 twins were higher than in singletons: PlGF 1.15 and 1.00 MoM, respectively ( P < 0.01); FF 1.35 and 1.01 MoM ( P < 0.0001). There was strong correlation between log PlGF and √FF: in singletons ( R = 0.257, P < 0.0001) and twins ( R = 0.221, although not significant P = 0.16). Applying the model retrospectively, 1 in 60 pre-term PE risk cut-off for singletons and 1 in 12 for twins classified 10.0% as screen-positive. Conclusion This preliminary theoretical model highlights the parameters requiring modification in a much larger series, and with pregnancy outcome data, before prospective evaluation of combined PlGF and FF screening for PE.