Development of a Third Trimester Contingent Prognostic Prediction Scheme for Suspected Early-Onset Pre-Eclampsia

Introduction: Short-term prediction of pre-eclampsia (PE) using soluble FMS-like tyrosine kinase-1 (sFlt-1)/ placental growth factor (PlGF) ratio has high false-positive rate. Therefore, we developed a prognostic prediction tool that predicts early-onset PE leading to delivery within 1 week on pregnancies with an sFlt-1/PlGF ratio above 38 and compared it with an analogous model based on sFlt-1/PlGF ratio and with the 655 sFlt-1/PlGF ratio cutoff.

Methods: Cohort study of 363 singleton pregnancies with clinical suspicion of PE before 34 weeks of gestation, allowing repeated assessments (522). 213 samples with an sFlt-1/PlGF ratio above 38 were assessed to construct and identify the best-fit linear mixed model. N-terminal pro-B-type natriuretic peptide (NT-proBNP), sFlt-1 MoM, PlGF MoM, and sFlt-1/PlGF ratio combined with gestational age (GA) were assessed.

Results: None of the pregnancies with an sFlt-1/PlGF ratio of 38 or below developed early-onset PE (309 samples from 240 pregnancies). Conversely, 47 women of 213 assessments (22.1%) with an sFlt-1/PlGF ratio above 38 developed the assessed outcome. The selected model included sFlt-1 MoM, NT-proBNP, and GA. Differences in area under the curve were observed between the selected model and the GA + sFlt-1/PlGF model (p = 0.04). At an sFlt-1/PlGF ratio cutoff of 655, detection rate was 31.9% (15/47), while the selected model detection was 55.3% (26/47) (p = 0.008).

Discussion: Considering repeated assessments, the sFlt-1/PlGF ratio of 38 or below adequately ruled out early-onset PE, leading to delivery within 1 week. However, when sFlt-1/PlGF ratio is above 38, the prediction tool derived from linear mixed model based on GA, NT-proBNP, and sFlt-1 MoM, provided a better prognosis prediction than the sFlt-1/PlGF ratio.