Prognostic value of maternal N‐terminal pro‐B‐type natriuretic peptide for prediction of severe maternal adverse outcome in women with pre‐eclampsia

OBJECTIVE: N-terminal pro-B-type natriuretic peptide (NT-proBNP), a marker of cardiac stress, has been proposed as a potential prognostic biomarker for maternal adverse outcome in pre-eclampsia (PE). This study aimed to evaluate the predictive value of NT-proBNP for severe maternal adverse outcome in pregnancies with an established diagnosis of PE. METHODS: This was a retrospective cohort study of singleton pregnancies diagnosed with PE ≤ 36 weeks of gestation that were assessed at the Medical University of Vienna between January 2018 and December 2023. Maternal serum levels of NT-proBNP, soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) were measured at the time of PE diagnosis. The primary outcome was the occurrence of a severe maternal adverse event, including intensive care unit admission, maternal death, pulmonary edema and severe neurological complications. Associations between severe maternal adverse outcome and Z-scores for NT-proBNP and the sFlt-1/PlGF ratio were analyzed using logistic and Cox regression models adjusted for gestational age at sampling and the Z-score of the other biomarker. The area under the receiver-operating-characteristics (ROC) curve (AUC) was used to assess the discriminative ability of the biomarkers. RESULTS: Of 130 women included in our cohort, 13 (10%) experienced severe maternal adverse outcome. NT-proBNP levels were significantly higher in this group (median, 688.0 (interquartile range (IQR), 249.6-1038.0) pg/mL vs 106.1 (IQR, 50.6-280.6) pg/mL; P < 0.001). Higher NT-proBNP Z-score was associated significantly with severe maternal adverse outcome (adjusted odds ratio, 3.24 (95% CI, 1.50-7.84); P = 0.005) and predicted shorter time-to-delivery with severe maternal adverse outcome (adjusted hazard ratio, 3.08 (95% CI, 1.47-6.44); P = 0.003) after adjusting for gestational age at sampling and sFlt-1/PlGF ratio Z-score. The sFlt-1/PlGF ratio was not associated significantly with these outcomes. ROC-curve analysis showed that NT-proBNP had superior discriminative performance compared with the sFlt-1/PlGF ratio (AUC, 0.75 (95% CI, 0.61-0.90) vs 0.67 (95% CI, 0.56-0.79)). The performance of both biomarkers improved when combined with gestational age at sampling (AUC, 0.82 (95% CI, 0.71-0.94) vs 0.76 (95% CI, 0.65-0.88)). CONCLUSION: NT-proBNP was a strong predictor of severe maternal adverse outcome and time-to-delivery in women diagnosed with PE, especially in early-onset cases. NT-proBNP may serve as a clinically accessible biomarker for risk stratification and surveillance in women with established PE.