The Plasma Proteome Is Associated with Anthropometric Status of Undernourished Nepalese School-Aged Children123

Abstract

Background: Malnutrition affects body growth, size, and composition of children. Yet, few functional biomarkers are known to be associated with childhood morphology. Objective: This cross-sectional study examined associations of anthropometric indicators of height, musculature, and fat mass with plasma proteins by using proteomics in a population cohort of school-aged Nepalese children. Methods: Height, weight, midupper arm circumference (MUAC), triceps and subscapular skinfolds, upper arm muscle area (AMA), and arm fat area (AFA) were assessed in 500 children 6–8 y of age. Height-for-age z scores (HAZs), weight-for-age z scores (WAZs), and body mass index–for-age z scores (BAZs) were derived from the WHO growth reference. Relative protein abundance was quantified by using tandem mass spectrometry. Protein-anthropometry associations were evaluated by linear mixed-effects models and identified as having a false discovery rate (q) <5%. Results: Among 982 proteins, 1, 10, 14, and 17 proteins were associated with BAZ, HAZ, MUAC, and AMA, respectively (q < 0.05). Insulin-like growth factor (IGF)-I, 2 IGF-binding proteins, and carnosinase-1 were associated with both HAZ and AMA. Proteins involved in nutrient transport, activation of innate immunity, and bone mineralization were associated with HAZ. Several extracellular matrix proteins were positively associated with AMA alone. The proteomes of MUAC and AMA substantially overlapped, whereas no proteins were associated with AFA or triceps and subscapular skinfolds. Myosin light-chain kinase, possibly reflecting leakage from muscle, was inversely associated with BAZ. The proteome of WAZ was the largest (n = 33) and most comprehensive, including proteins involved in neural development and oxidative stress response, among others. Conclusions: Plasma proteomics confirmed known biomarkers of childhood growth and revealed novel proteins associated with lean mass in chronically undernourished children. Identified proteins may serve as candidates for assessing growth and nutritional status of children in similar undernourished settings. The antenatal micronutrient supplementation trial yielding the study cohort of children was registered at clinicaltrials.gov as NCT00115271.