TY - JOUR
T1 - Maternal 12-HETE is associated with childhood asthma and the responses to prenatal omega-3 supplementation
AU - Chen, Liang
AU - Brustad, Nicklas
AU - Thorsen, Jonathan
AU - Wang, Tingting
AU - Ali, Mina
AU - Kyvsgaard, Julie N.
AU - Lovric, Mario
AU - Ebrahimi, Parvaneh
AU - Luo, Yang
AU - Pedersen, Casper Emil T.
AU - Prince, Nicole
AU - Kelly, Rachel S.
AU - Schoos, Ann Marie M.
AU - Vahman, Nilo
AU - Rasmussen, Morten A.
AU - Brix, Susanne
AU - Litonjua, Augusto A.
AU - Weiss, Scott T.
AU - Wheelock, Craig E.
AU - Lasky-Su, Jessica
AU - Bønnelykke, Klaus
AU - Stokholm, Jakob
AU - Chawes, Bo
N1 - Publisher Copyright:
© 2026 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/
PY - 2026/3/17
Y1 - 2026/3/17
N2 - SummaryA 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.
AB - SummaryA 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.
KW - 12-HETE
KW - 12-hydroxyeicosatetraenoic acid
KW - airway immune profiles
KW - childhood asthma
KW - COPSAC
KW - infant airway microbiome
KW - n-3 LCPUFA
KW - oxylipins
KW - precision prevention
KW - prenatal omega-3 supplementation
KW - respiratory infections
KW - VDAART
UR - https://www.scopus.com/pages/publications/105033747872
U2 - 10.1016/j.xcrm.2026.102689
DO - 10.1016/j.xcrm.2026.102689
M3 - Journal article
C2 - 41850235
AN - SCOPUS:105033747872
SN - 2666-3791
VL - 7
JO - Cell Reports Medicine
JF - Cell Reports Medicine
IS - 3
M1 - 102689
ER -