N-terminal pro-B-type natriuretic peptide in the circulation of fetuses with cardiac malformations

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.