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 International Society of Ultrasound in Obstetrics and Gynecology.

Keywords: NT‐proBNP; N‐terminal pro B‐type natriuretic peptide; PlGF; angiogenic markers; placental complication; placental growth factor; pre‐eclampsia; sFlt‐1; soluble fms‐like tyrosine kinase‐1.