Low serum ω-3 and ω-6 polyunsaturated fatty acids and other metabolites are associated with poor linear growth in young children from rural Malawi

Background: Stunting affects similar to 25% of children <5 y of age and is associated with impaired cognitive and motor development and increased morbidity and mortality. The pathogenesis of stunting is poorly understood. Objective: The purpose of this study was to identify altered metabolic pathways associated with child stunting. Design: We measured 677 serum metabolites using liquid chromatography-tandem mass spectrometry in a cross-sectional study of 400 Malawian children aged 12-59 mo, of whom 62% were stunted. Results: A low height-for-age z score (HAZ) was associated with lower serum concentrations of 1) omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs), 2) sulfated neurosteroids, which play a role in brain development, 3) carnitine, a conditionally essential nutrient with an important role in the carnitine shuttle for the metabolism of fatty acids and energy production, and 4) gamma-glutamyl amino acids, which represent an altered gamma-glutamyl cycle of glutathione metabolism. A low HAZ was associated with significantly higher serum concentrations of 5 biomarkers related to cigarette smoke exposure. Conclusions: This metabolomics study shows a cross-sectional association between stunting and low serum omega-3 and omega-6 long-chain PUFAs, which are essential for growth and development; low sulfated neurosteroids, which play a role in brain development; low carnitine, which is essential for beta-oxidation of fatty acids; alterations in glutathione metabolism; and increased serum metabolites that are associated with secondhand tobacco smoke exposure.