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

Background: The association between lower first-trimester N-terminal pro B-type natriuretic peptide (NT-proBNP) levels and increased pre-eclampsia risk remains poorly understood, contrasting with the elevated NT-proBNP levels observed at the time of pre-eclampsia diagnosis. Objectives: The aim of this study was to assess the utility of third-trimester NT-proBNP for assessing pre-eclampsia risk before onset. 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 (Q1-Q3: 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 significantly associated with increased risk of pre-eclampsia within 4 weeks but reduced risk beyond 4 weeks. After adjusting for age, body mass index, nulliparity, systolic blood pressure, and the sFlt-1/PlGF ratio, the adjusted OR was 2.18 (95% CI: 0.88-5.42, P = 0.09) for onset within 4 weeks and 0.72 (95% CI: 0.55-0.93, P = 0.012) 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. Conclusions: 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.