Cardiac Biomarkers in Children with Severe Acute Malnutrition in Low- and Middle-Income Countries

Abstract

Background: Acute malnutrition affects approximately 45 million children under five globally and significantly increases mortality risk. While cardiac abnormalities have been described in children with severe acute malnutrition (SAM), the degree and clinical relevance of cardiac dysfunction remain controversial. Cardiac biomarkers provide a means to evaluate cardiovascular function but have not been widely studied in pediatric malnutrition contexts.Objective: To examine differences in cardiac biomarker levels between children with varying degrees of acute malnutrition and investigate associations between nutritional status and cardiovascular indicators. Methods: This analysis utilized data from the Childhood Acute Illness and Nutrition (CHAIN) Network nested case-cohort study. The analysis included 1,526 hospitalized children aged 2-23 months with available cardiac biomarker measurements and 297 community children as reference. Children were categorized into four nutritional groups: no acute malnutrition, moderate acute malnutrition (MAM), SAM without edema, and SAM with edema, using WHO criteria combining weight-for-height z-scores and mid-upper arm circumference. Cardiac biomarkers (Troponin T, Troponin I, Troponin I2, NT-proBNP, Galectin-3, and Periostin) were measured using plasma samples. Linear regression models examined associations between nutritional status and log-transformed biomarker levels, adjusting for demographic factors and clinical severity indicators. Results: The sample comprised 521 (34.1%) children without acute malnutrition, 278 (18.2%) with MAM, 439 (28.8%) with SAM without edema, and 288 (18.9%) with SAM with edema. Five of six cardiac biomarkers showed significant differences across nutritional groups in crude analyses. After comprehensive adjustment for clinical factors, NT-proBNP (β=0.26, 95% CI: 0.12-0.41, p<0.001) and Galectin-3 (β=0.14, 95% CI: 0.09-0.19, p<0.001) remained significantly associated with acute malnutrition, indicating 26% and 14% higher levels respectively in children with acute malnutrition compared to those without. Children with edematous SAM showed markedly elevated Galectin-3 levels compared to non-edematous SAM, suggesting distinct pathophysiological mechanisms. Most biomarkers improved toward community levels at discharge, indicating potential reversibility with treatment. Conclusions: Acute malnutrition is associated with elevated NT-proBNP and Galectin-3 levels, suggesting ventricular strain and inflammatory processes that persist after adjustment for acute illness severity. The distinct biomarker pattern in edematous versus non-edematous SAM provides biochemical evidence for different underlying mechanisms between these malnutrition phenotypes. These findings contribute novel insights into cardiovascular implications of childhood malnutrition, though the clinical significance requires further investigation with functional cardiac assessments.