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Relationship Between Serum Brain-Type Natriuretic Peptide and Biomarkers of Growth in Infants With Shunt-Dependent
Monique M Gardner1, Jennifer Faerber2, Andrew C Glatz3
1Division of Cardiac Critical Care, Department of Anesthesiology and Critical Care, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Insights
Poor growth in infants with single ventricle heart disease is linked to heart failure. This study found an inverse correlation between brain natriuretic peptide (BNP) and growth factors, suggesting heart failure impacts infant growth.
Area of Science:
- Pediatric Cardiology
- Neonatology
- Growth Factor Research
Background:
- Infants with single ventricle heart disease often experience poor growth, impacting neurodevelopmental outcomes.
- The relationship between heart failure and growth factors in this population remains poorly understood.
- Current nutritional interventions primarily focus on weight gain, with limited attention to underlying physiological mechanisms.
Purpose of the Study:
- To investigate the association between heart failure, measured by brain natriuretic peptide (BNP), and key growth factors.
- To explore the relationship between BNP, insulin-like growth factor 1 (IGF-1), and insulin-like growth factor-binding protein 3 (IGFBP-3) in infants with single ventricle heart disease.
- To analyze these relationships at critical time points during neonatal intervention and surgical palliation.
Main Methods:
- A prospective observational pilot study involving 38 infants with single ventricle heart disease.
- Measurement of BNP, IGF-1, and IGFBP-3 at three distinct time points: pre-discharge, pre-superior cavopulmonary connection (SCPC), and post-SCPC discharge.
- Statistical analysis using Spearman correlations and linear mixed-effects models to assess relationships between BNP and growth factors over time.
Main Results:
- Median BNP levels were elevated initially and decreased over the study period.
- Median IGF-1 Z-scores were below normal but showed improvement over time.
- An inverse correlation was observed between BNP and IGF-1, and between BNP and IGFBP-3, particularly at specific time points and when analyzing changes over time (p < 0.10).
Conclusions:
- This pilot study suggests a mechanistic link between the heart failure state and impaired growth in infants with single ventricle heart disease.
- The observed inverse correlation between BNP and growth factors highlights the potential role of cardiac dysfunction in growth trajectories.
- Further research is warranted to elucidate the complex interplay between heart failure and growth in this vulnerable pediatric population.
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 (287 pg/dl [interquartile range 147 to 794], 85 pg/dl [52 to 183], and 90 pg/dl [70 to 138]). Median IGF-1 Z score 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 Z score 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.
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