Serum metabolic signatures of nutritional status in early childhood: results from the Brazilian National Survey on Child Nutrition (ENANI-2019)

BACKGROUND: Untargeted metabolic profiling may provide biochemical insights into adverse growth outcomes in early childhood. We aimed to investigate the association between serum metabolic signatures and anthropometric indicators in young children. METHODS: The serum metabolome of 4978 children aged 6-59 months, studied by the 2019 Brazilian National Survey on Child Nutrition (ENANI-2019), was analyzed using multi-segment injection-capillary electrophoresis-mass spectrometry. WHO length/height-for-age (HAZ), weight-for-height (WHZ), body-mass-index-for-age (BMIZ), and weight-for-age (WAZ) indices, and stunting (HAZ <-2) and overweight (WHZ > 2) were the outcomes. Partial least squares regression was used to select serum metabolites with a variable importance projection ≥ 1. Linear and logistic regression models, adjusted for confounders and sex-stratified, were fitted. The Benjamini-Hochberg correction (adjusted p < 0.05) controlled the false discovery rate. RESULTS: Tyrosine, creatinine, and 5-aminovaleric acid were consistently directly associated with all anthropometric indices. Threonine was directly associated with HAZ. The branched-chain amino acids were directly associated with WHZ. Leucine, valine, lysine, and carnitine were directly associated with BMIZ, whereas 3-hydroxybutyric acid was inversely associated with WAZ. Direct associations between methionine and WHZ, BMIZ, and WAZ, and between histidine and WHZ and BMIZ, were observed exclusively in girls, while hippuric acid and cresol sulfate were inversely associated with HAZ, and phenylacetylglutamine with WAZ, exclusively in boys. Further, 2-aminobutyric acid and creatinine were inversely associated with stunting, and proline betaine was inversely associated with being overweight. CONCLUSION: Serum metabolomics offers a valuable tool for screening for childhood malnutrition, and key metabolites were associated with energy and muscle metabolism, the endocrine system, and aspects of the human diet.