N‐terminal pro B‐type natriuretic peptide as biomarker to predict pre‐eclampsia and maternal–fetal complications

ABSTRACT Objective A soluble fms‐like tyrosine kinase‐1 (sFlt‐1)‐to‐placental growth factor (PlGF) ratio cut‐off of 38 is currently considered optimal for ruling out pre‐eclampsia (PE); however, implementation of this ratio in clinical practice is limited. N‐terminal pro B‐type natriuretic peptide (NT‐proBNP) is elevated in PE owing to the cardiovascular effects of this disease. This study aimed to identify the predictive performance of NT‐proBNP to detect PE and placental complications within 1 week after assessment, and compare it with the predictive performance of the sFlt‐1/PlGF ratio. High‐sensitivity troponin T (hs‐TnT) and uric acid were also evaluated. Methods This was a prospective nested case–control study conducted in five Spanish centers between March 2018 and December 2020, and comprised women with a singleton pregnancy and suspected PE between 24 + 0 and 41 + 0 weeks' gestation. We evaluated the ability of the sFlt‐1/PlGF ratio, NT‐proBNP, hs‐TnT and uric acid to predict the development of any‐onset (at any gestational age), early‐onset (before 34 weeks) or term (at or after 37 weeks) PE within 1 week or 4 weeks after assessment. Predictive performance was assessed by estimating negative predictive values, positive predictive values, sensitivity, specificity and areas under the receiver‐operating‐characteristics curves (AUCs) for these biomarkers, with corresponding 95% CIs. We performed post‐hoc exploratory analyses of associations between the sFlt‐1/PlGF ratio, NT‐proBNP, hs‐TnT and uric acid in women who developed PE, as well as in women who developed complicated PE (PE plus fetal growth restriction, stillbirth or placental abruption) within 1 week and 4 weeks after assessment. Results A total of 323 women with suspected PE at or before 41 + 0 weeks were enrolled in the study, of whom seven were lost to follow‐up. The final analysis included 316 eligible participants, with 424 samples. The overall incidence of PE was 23.4% ( n = 74) and early‐onset PE developed in 8.5% ( n = 27) of cases. The sFlt‐1/PlGF ratio and NT‐proBNP exhibited similar abilities to predict early‐onset PE within 1 week after assessment (AUC, 0.970 (95% CI, 0.932–1.000) and 0.971 (95% CI, 0.942–1.000), respectively). hs‐TnT and uric acid demonstrated inferior predictive capability compared with the sFlt‐1/PlGF ratio for the prediction of any‐onset PE, early‐onset PE and term PE within 1 week and 4 weeks after assessment. The optimal cut‐off for NT‐proBNP was 116 pg/mL. At this cut‐off, NT‐proBNP showed a sensitivity of 90.9% (95% CI, 70.8–98.9%) and a specificity of 94.3% (95% CI, 91.2–96.5%), with a positive predictive value of 5.7% (95% CI, 3.7–8.7%) and a negative predictive value of 99.9% (95% CI, 99.9–100%) in predicting early‐onset PE within 1 week of assessment, which was comparable with that of the sFlt‐1/PlGF ratio. Participants with PE‐related complications had higher levels of all biomarkers, but only NT‐proBNP showed a similar predictive ability to the sFlt‐1/PlGF ratio for complicated PE within 1 week after assessment (AUC, 0.818 (95% CI, 0.706–0.930) vs 0.822 (95% CI, 0.723–0.921), respectively). Conclusion An NT‐proBNP cut‐off value of 116 pg/mL has a similar diagnostic performance to that of the sFlt‐1/PlGF ratio in predicting the diagnosis of early‐onset PE within 1 week after assessment. Thus, NT‐proBNP could be used in clinical practice for the early identification and management of PE, particularly in cases for which the sFlt‐1/PlGF ratio is not available. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.