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.

Stunting affects ∼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. The purpose of this study was to identify altered metabolic pathways associated with child stunting. 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. A low height-for-age score (HAZ) was associated with lower serum concentrations of ) ω-3 (n-3) and ω-6 (n-6) polyunsaturated fatty acids (PUFAs), ) sulfated neurosteroids, which play a role in brain development, ) carnitine, a conditionally essential nutrient with an important role in the carnitine shuttle for the metabolism of fatty acids and energy production, and ) γ-glutamyl amino acids, which represent an altered γ-glutamyl cycle of glutathione metabolism. A low HAZ was associated with significantly higher serum concentrations of 5 biomarkers related to cigarette smoke exposure. This metabolomics study shows a cross-sectional association between stunting and low serum ω-3 and ω-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 β-oxidation of fatty acids; alterations in glutathione metabolism; and increased serum metabolites that are associated with secondhand tobacco smoke exposure. This trial was registered at www.controlled-trials.com as ISRCTN14597012.