Third-Trimester NT-proBNP for Pre-eclampsia Risk Prediction

Lucas Bacmeister, MD; Annette Buellesbach, MD; Dorte Glintborg, MD, PhD; Jan Stener Jorgensen, MD, PhD; Birgitte Møller Luef, MD; Anna Birukov, PhD; Adrian Heidenreich, MD; Diana Lindner, PhD; Till Keller, MD; Kristin Kraeker, PhD; Tanja Zeller, PhD; Ralf Dechend, MD; Marianne Skovsager Andersen, MD, PhD; Dirk Westermann, MD

doi:10.1016/j.jacadv.2025.101671

JACC: Advances (Apr 2025)

Third-Trimester NT-proBNP for Pre-eclampsia Risk Prediction

Lucas Bacmeister, MD,
Annette Buellesbach, MD,
Dorte Glintborg, MD, PhD,
Jan Stener Jorgensen, MD, PhD,
Birgitte Møller Luef, MD,
Anna Birukov, PhD,
Adrian Heidenreich, MD,
Diana Lindner, PhD,
Till Keller, MD,
Kristin Kraeker, PhD,
Tanja Zeller, PhD,
Ralf Dechend, MD,
Marianne Skovsager Andersen, MD, PhD,
Dirk Westermann, MD

Affiliations

Lucas Bacmeister, MD: Clinic for Cardiology and Angiology, University Heart Center Freiburg – Bad Krozingen, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Address for correspondence: Dr Lucas Bacmeister, University Heart Center Freiburg – Bad Krozingen, Department of Cardiology & Angiology, University Medical Center Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany.
Annette Buellesbach, MD: Clinic for Cardiology and Angiology, University Heart Center Freiburg – Bad Krozingen, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
Dorte Glintborg, MD, PhD: Department of Endocrinology, Odense University Hospital, University of Southern Denmark, Odense, Denmark; Institute for Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
Jan Stener Jorgensen, MD, PhD: Institute for Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Department of Obstetrics and Fetal Medicine, Odense University Hospital, University of Southern Denmark, Odense, Denmark
Birgitte Møller Luef, MD: Institute for Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Department of Obstetrics and Fetal Medicine, Odense University Hospital, University of Southern Denmark, Odense, Denmark
Anna Birukov, PhD: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
Adrian Heidenreich, MD: Clinic for Cardiology and Angiology, University Heart Center Freiburg – Bad Krozingen, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
Diana Lindner, PhD: Clinic for Cardiology and Angiology, University Heart Center Freiburg – Bad Krozingen, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
Till Keller, MD: Clinic for Cardiology and Angiology, University Heart Center Freiburg – Bad Krozingen, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
Kristin Kraeker, PhD: Experimental and Clinical Research Center, A Cooperation Between the Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association and the Charité - Universitätsmedizin Berlin, Berlin, Germany
Tanja Zeller, PhD: Department of Cardiology, University Heart and Vascular Center Hamburg, Medical University Hamburg-Eppendorf, Hamburg, Germany; Institute for Cardiogenetics, University of Luebeck, University Hospital Schleswig-Holstein, Luebeck, Germany; German Center for Cardiovascular Research, DZHK, Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany
Ralf Dechend, MD: Experimental and Clinical Research Center, A Cooperation Between the Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association and the Charité - Universitätsmedizin Berlin, Berlin, Germany; Department of Cardiology and Nephrology, HELIOS Clinic, Berlin, Germany
Marianne Skovsager Andersen, MD, PhD: Department of Endocrinology, Odense University Hospital, University of Southern Denmark, Odense, Denmark; Institute for Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
Dirk Westermann, MD: Clinic for Cardiology and Angiology, University Heart Center Freiburg – Bad Krozingen, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

DOI: https://doi.org/10.1016/j.jacadv.2025.101671
Journal volume & issue: Vol. 4, no. 4
p. 101671

Abstract

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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.

Published in JACC: Advances

ISSN: 2772-963X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the circulatory (Cardiovascular) system; Medicine: Internal medicine: Medical emergencies. Critical care. Intensive care. First aid
Website: https://www.sciencedirect.com/journal/jacc-advances

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