B-Type Natriuretic Peptides Are a Marker for Congenital Heart Disease in Neonates

Undiagnosed heart conditions in neonates may have dramatic consequences, as a number of conditions, including critical congenital heart defects (CHD), may have sudden cardiac death as initial presentation. The American Heart Association Congenital Heart Defects Committee of the Council on Cardiovascular Disease in the Young (1) recently published an advisory on the evaluation of screening approaches for heart disease in children and adolescents. According to this guideline (1), a neonatal screening program for CHD would be advised; however, various issues need to be evaluated, including costs and the difficulty to separate out those neonates requiring a full cardiac examination. It is conceivable that a low-cost, feasible, accurate, and reproducible laboratory test could help in this setting. The measurement of circulating B-type cardiac natriuretic peptide (BNP) and its related peptides (such as the N-terminal fragment of proBNP and NT-proBNP) is considered a useful index of myocardial function. International guidelines currently recommend the use of BNP and NT-proBNP immunoassay methods for the diagnosis and risk stratification of adult patients with acute and chronic heart failure (2–4). Recent studies suggest that the measurement of BNP and NT-proBNP could be considered as a valid tool even for the diagnosis of CHD in pediatric patients (5). In this issue of Pediatric Critical Care Medicine, Lechner and colleagues (6) investigated NT-proBNP concentration and its time course during the first 5 days of life in neonates with CHD compared with neonates with respiratory distress (RD). Authors measured NT-proBNP levels of 40 neonates with arterial duct–dependent CHD and of 40 neonates with RD but not CHD on the first, second, third, and fifth day of life. Authors conclude that NT-proBNP cannot differentiate between CHD and RD in the neonate on the first day of life. However, from the second day onwards, NT-proBNP in neonates with CHD shows higher values and a different time course, enabling the differential diagnosis between CHD and RD, due to other than cardiac reasons. These data are well in agreement with previous findings from our laboratory, showing a better diagnostic accuracy of BNP assay for CHD after the first week than in the first day of life (5, 7). In healthy neonates, BNP and NT-proBNP levels are very high in the first 4 days, then peptide values fall rapidly during the first week, with a further slower progressive reduction throughout the first month of life (5). The elevation of BNP and NT-proBNP levels observed in the first day of life is substantially due to the physiological maturation process of cardiomyocytes, and negatively influences the diagnostic accuracy of the biomarker for CHD diagnosis (5). A huge biomarker variability during the first days of life makes difficult the clinical interpretation of the assay results; therefore, an accurate diagnosis of CHD in neonates strongly depends on reliable reference and decisional values for BNP and NT-proBNP assays for neonatal age (5). Several recent studies (5–7) stress the potential role of B-type natriuretic peptides as biomarkers for CHD in neonates. BNP can be measured with a point-of-care testing method also in capillary blood specimens, allowing a less invasive, feasible approach for newborns. BNP may be included in a sustainable neonatal screening program for CHD, together with conventional exams, such as electrocardiogram and pulsoximetry (1). Further studies are, however, needed in order to demonstrate a favorable cost–benefit ratio for B-type natriuretic peptide testing in CHD pediatric patients.