Third-Trimester NT-proBNP for Pre-eclampsia Risk Prediction: A Comparison with sFlt-1/PlGF in a Population-Based Cohort

Clin Res Cardiol (2025). DOI 10.1007/s00392-025-02625-4
L. Bacmeister (Freiburg im Breisgau)¹, A. Büllesbach (Bad Krozingen)², D. Lindner (Freiburg im Breisgau)¹, A. Heidenreich (Freiburg im Breisgau)¹, T. Keller (Bad Krozingen)², R. Dechend (Berlin)³, M. Andersen (Odense)⁴, D. Westermann (Freiburg im Breisgau)^5
1Universitäts-Herzzentrum Freiburg - Bad Krozingen Klinik für Kardiologie und Angiologie Freiburg im Breisgau, Deutschland; ²Universitäts-Herzzentrum Freiburg / Bad Krozingen Klinik für Kardiologie und Angiologie Bad Krozingen, Deutschland; ³HELIOS Klinikum Berlin-Buch Klinik und Poliklinik für Kardiologie und Nephrologie Berlin, Deutschland; ⁴Odense University Hospital Department for Endocrinology Odense, Dänemark; ⁵Universitäts-Herzzentrum Freiburg - Bad Krozingen Innere Medizin III, Kardiologie und Angiologie Freiburg im Breisgau, Deutschland

Background
The association between lower first-trimester N-terminal pro B-type natriuretic peptide (NT-proBNP) levels and increased pre-eclampsia risk contrasts with elevated levels of NT-proBNP at the time of pre-eclampsia diagnosis. However, the utility of third-trimester NT-proBNP for assessing pre-eclampsia risk before onset remains unclear.

Methods
NT-proBNP and the soluble Fms-like tyrosine kinase 1 to placental growth factor ratio (sFlt-1/PlGF) were measured in 1,476 pregnant individuals from the Odense Child Cohort at a median gestational age of 29 weeks (IQR: 28.4–29.4). Pre-eclampsia cases were categorized by timing: 11 individuals (0.7%) developed pre-eclampsia within 4 weeks, while 110 (7.5%) developed pre-eclampsia more than 4 weeks after sampling.

Results
Higher NT-proBNP levels were associated with increased risk of pre-eclampsia within 4 weeks but reduced risk beyond 4 weeks. These associations remained significant after adjusting for age, body mass index, nulliparity, systolic blood pressure, and the sFlt-1/PlGF ratio (adjusted odds ratio = 2.70, 95% confidence interval: 1.05–7.65, p = 0.044 for onset within 4 weeks; adjusted odds ratio = 0.66, 95% confidence interval: 0.51–0.85, p = 0.001 for onset beyond 4 weeks). However, combining NT-proBNP with the sFlt-1/PlGF ratio did not improve the predictive accuracy for short- or long-term pre-eclampsia risk compared to the sFlt-1/PlGF ratio alone.

Conclusion
Unselected NT-proBNP screening in the early third trimester has limited clinical value for predicting short- or long-term pre-eclampsia risk when compared to angiogenic biomarkers.