Relationship Between Serum Brain-Type Natriuretic Peptide and Biomarkers of Growth in Infants With Shunt-Dependent Single Cardiac Ventricle

Abstract

For infants with shunt-dependent or ductal-dependent single ventricle heart disease, poor growth is common and associated with morbidity and impaired neurodevelopmental outcomes. Although attention has focused on nutrition to promote weight gain, little is known about the relation between heart failure and growth factors. A prospective observational pilot study was performed to assess the relation between heart failure, assessed by brain natriuretic peptide (BNP), and growth factors (insulin-like growth factor 1 [IGF-1] and insulin-like growth factor-binding protein 3) at 3 visits: (1) before discharge from neonatal intervention with the establishment of stable pulmonary blood flow, (2) immediately before superior cavopulmonary connection, and (3) before discharge after superior cavopulmonary connection operation. The relation between BNP and growth factors was analyzed using Spearman pairwise correlations at each visit and modeled over time with a linear mixed-effects model. Correlations were considered worthy of further exploration using a p <0.10, given the exploratory nature of the study. The study included 38 infants (66% male, 68% hypoplastic left heart syndrome). Median BNP was elevated at visit 1 and decreased over time (287pg/dl [interquartile range 147 to 794], 85pg/dl [52 to 183], and 90pg/dl [70 to 138]). Median IGF-1 Zscore was <0 at each visit but increased over time (-0.9 [interquartile range -1.1 to 0.1], -0.7 [-1.2 to 0.1], and -0.5 [-1.2 to 0]). Inverse correlations were found between BNP and IGF-1 at visit 1 (r=-0.40, p=0.097), BNP and IGF-1 and insulin-like growth factor-binding protein 3 at visit 2 (r=-0.33, p=0.080 and r=-0.33, p=0.085, respectively) and BNP and IGF-1 Zscore at visit 3 (r=-0.42, p=0.049). Significant relations were likewise found between the change in BNP and the change in IGF-1 between visits 1 and 3 (p=0.046) and between visits 2 and 3 (p=0.048). In conclusion, this pilot study demonstrates an inverse correlation between BNP and growth factors, suggesting that the heart failure state associated with this physiology may play a mechanistic role in impaired growth.