Can NT-proBNP Enhance the Accuracy of Angiogenic Factors in the Short-Term Prediction of Preeclampsia?

Abstract

Background Angiogenic biomarkers aid in short-term prediction of preeclampsia (PE) but are often limited by false-positive results. N-terminal pro–B-type natriuretic peptide (NT-proBNP), which is elevated in PE due to cardiovascular dysfunction, may enhance diagnostic precision. This study evaluated whether adding NT-proBNP to the soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio improves prediction of PE and associated complications within 1 week.

Methods We performed a prospective multicenter case-control study in pregnancies with suspected PE between 24 + 0 and 41 + 0 weeks. Three models evaluated the addition of NT-proBNP (cutoff ≥116 pg/mL) to the sFlt-1/PlGF ratio using thresholds <38, ≥85, and 38 to 84. All models were assessed for early-onset, preterm, term, and overall PE prediction using receiver operating curve analysis, predictive metrics, and Kaplan–Meier survival curves.

Results A total of 316 women (424 serum samples) were included. PE occurred in 23.4% of cases, including 8.5% early-onset PE. NT-proBNP levels were significantly elevated in PE cases. The addition of NT-proBNP improved early-onset PE prediction, particularly in intermediate-risk cases (sFlt-1/PlGF 38–84), achieving an area under the curve (AUC) of 0.949 and a negative predictive value (NPV) of 99.5%, outperforming sFlt-1/PlGF alone. Survival analysis revealed a shorter median time to delivery when both biomarkers were elevated (1.3 vs 4.0 weeks; P < 0.001). For term PE, NT-proBNP increased positive predictive value when combined with sFlt-1/PlGF ≥ 38. In complicated PE, the combined model improved specificity (77.4%) and AUC (0.770), with an NPV of 91.1%.

Conclusions NT-proBNP enhances the short-term predictive performance of the sFlt-1/PlGF ratio, particularly in intermediate-risk cases. This multimarker approach may refine risk stratification and support timely clinical intervention in pregnancies at risk of PE.