The Role of Biomarkers in Predicting Pre-Eclampsia in High-Risk Women.

Background There are limited data on performance of biomarkers to predict pre-eclampsia (PE) in high-risk women. This study investigated the ability of FABP4, PAPP-A, PlGF, sFlt-1 and sEng to predict PE in a high-risk group. Methods Non-fasting samples were analysed at 11 + 0–13 + 6 (V1) and 19 + 0–21 + 6 weeks (V2) ( n = 195). Logistic regression models were determined. Area under (AUC) the receiver operating characteristic (ROC) curve analysis was performed. The added value of biomarkers to clinical characteristics for PE prediction was quantified using integrated discrimination improvement (IDI) and net reclassification improvement (NRI) indices. Results Prevalence of PE was 12%. Lower concentrations of sFlt-1:PlGF (V1) and PlGF and PlGF:sEng (V2) were seen in women who developed PE. Controlling for baseline characteristics (V1), a doubling of sFlt-1 (pg/mL) (median 896.0, IQR 725.5–1097.0) and sFlt-1:PlGF (median 21.2, IQR 14.7–32.3) was associated with reduction in odds of PE (OR 0.20, 95% CI 0.06–0.65, P = 0.007 and OR 0.48, 95% CI 0.25–0.92, P = 0.04). Addition of sFlt-1 and sFlt-1:PlGF to baseline characteristics non-significantly improved AUC (0.74) (AUC 0.77, P = 0.40 and 0.76, P = 0.39). NRI and IDI analyses confirmed added clinical utility of sFlt-1 (NRI = 0.539, P = 0.01 and IDI = 0.052, P = 0.03). In V2, doubling of PlGF:sEng (median 71.9, IQR 47.0–102.8) was associated with reduction in the risk of PE (OR 0.56, 95% CI 0.35–0.98, P = 0.04). The addition of PlGF:sEng to baseline characteristics non-significantly improved AUC from 0.78 to 0.82 ( P = 0.25) and improved reclassification of cases (NRI = 0.682, P = 0.002). Conclusions Screening tests incorporating first trimester sFlt-1 and second trimester PlGF:sEng have potential to aid PE prediction in high-risk pregnancies.