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

https://doi.org/10.1007/s00392-025-02625-4

Lucas 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.
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