Maternal 12-HETE is associated with childhood asthma and the responses to prenatal omega-3 supplementation

A recent mouse study has shown that deficiency in 12-hydroxyeicosatetraenoic acid (12-HETE) affects neonatal alveolar macrophage imprinting and associates with increased respiratory morbidity, but this has not been investigated in humans. Utilizing data from two mother-child cohorts, COPSAC₂₀₁₀ and VDAART, we demonstrate that undetectable maternal plasma 12-HETE during pregnancy associates with increased risk of childhood asthma and respiratory infections alongside an altered infant airway microbiota structure and airway immune profile. Further, we observed an interaction between maternal 12-HETE levels and maternal N-3 long-chain polyunsaturated fatty acid (n-3 LCPUFA) supplementation in a randomized clinical trial in COPSAC₂₀₁₀ and maternal dietary n-3 LCPUFA intake in VDAART in relation to offspring respiratory morbidity; higher prenatal n-3 LCPUFA exposure reduced asthma and respiratory infection among mothers with detectable 12-HETE levels. These findings identify maternal 12-HETE as a potential biomarker for risk of offspring respiratory morbidity and suggest that maternal 12-HETE status may determine responsiveness to prenatal n-3 LCPUFA supplementation.