title: N-terminal pro-B-type natriuretic peptide in the circulation of fetuses with cardiac malformations.
abstract: Cardiac malformations with impact on loading patterns have the potential to progress to irreversible loss of ventricular function during human fetal life. N-terminal pro-B-type natriuretic peptide (nt-proBNP) is a marker of cardiac dysfunction and involved in cardiac remodeling and fibrosis. We evaluated nt-proBNP levels in the circulation of human fetuses with cardiac defects. A total of 45 cases and 75 controls during the second half of gestation were recruited. Nt-proBNP concentrations were determined in venous specimens obtained by fetal blood sampling. Results were correlated to echocardiography and Doppler studies. Mean gestational age was 26.9 weeks (range 21.0-33.4 weeks). Levels of circulating nt-proBNP were elevated in fetuses with cardiac defects (mean 6,896 ng/L (range 595-42,479 ng/L) vs. 1,867 ng/L (73-3,751 ng/L), p < 0.001). In the presence of abnormal Doppler indices a further increase was detected (mean 11,287 ng/L (range 1,403-42,479 ng/L) vs. 4,659 ng/L (595-30,848 ng/L), p = 0.021). No difference was found in fetuses with co-existing growth restriction. Malformations were classified according to their hemodynamic effect. Compared to shunt defects nt-proBNP concentrations were significantly higher in left or right ventricular outflow tract obstruction with intact ventricular septum (mean 15,639 ng/L (range 2,301-42,479 ng/L) vs. 3,891 ng/L (595-13,752 ng/L), p = 0.013), and corresponded to the degree of ventricular dysfunction. In the circulation of human fetuses with cardiac defects levels of circulating nt-proBNP are elevated. Concentrations correlate with the type of myocardial wall stress. This finding supports a role for nt-proBNP as early indicator of intrauterine cardiovascular dysfunction and cardiac remodeling.
authors.affiliation: Department of Obstetrics and Prenatal Medicine, University of Bonn Medical School, Sigmund-Freud-Str. 25, 53105, Bonn, Germany. waltraut.merz@ukb.uni-bonn.de
authors.forename: Waltraut M
authors.initials: WM
authors.lastname: Merz
authors.forename: Kirsten
authors.initials: K
authors.lastname: Kübler
authors.forename: Eike
authors.initials: E
authors.lastname: Albers
authors.forename: Birgit
authors.initials: B
authors.lastname: Stoffel-Wagner
authors.forename: Ulrich
authors.initials: U
authors.lastname: Gembruch
mesh_terms: D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D015150:Echocardiography, Doppler; D005312:Fetal Blood / Q000737:chemistry*; D005318:Fetal Heart / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D005858:Germany; D005865:Gestational Age; D006330:Heart Defects, Congenital / Q000097:blood* / Q000000981:diagnostic imaging / Q000196:embryology / Q000503:physiopathology; D006801:Humans; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D016216:Ultrasonography, Prenatal; D015854:Up-Regulation; D016277:Ventricular Function, Left; D016278:Ventricular Function, Right; D020257:Ventricular Remodeling
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain