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

**Authors:** Liang Chen, Nicklas Brustad, Jonathan Thorsen, Tingting Wang, Mina Ali, Julie N. Kyvsgaard, Mario Lovric, Parvaneh Ebrahimi, Yang Luo, Casper-Emil T. Pedersen, Nicole Prince, Rachel S. Kelly, Ann-Marie M. Schoos, Nilo Vahman, Morten A. Rasmussen, Susanne Brix, Augusto A. Litonjua, Scott T. Weiss, Craig E. Wheelock, Jessica Lasky-Su, Klaus Bønnelykke, Jakob Stokholm, Bo Chawes

PMC · DOI: 10.1016/j.xcrm.2026.102689 · Cell Reports Medicine · 2026-03-17

## TL;DR

Low levels of a fatty acid called 12-HETE in mothers during pregnancy may increase children's asthma risk, and omega-3 supplements may help if 12-HETE is present.

## Contribution

Identifies maternal 12-HETE as a potential biomarker for childhood asthma risk and response to prenatal omega-3 supplementation.

## Key findings

- Low maternal 12-HETE levels during pregnancy are linked to higher childhood asthma and respiratory infection risks.
- Prenatal omega-3 intake reduces asthma risk in children only when maternal 12-HETE is detectable.
- 12-HETE levels correlate with infant airway microbiota and immune profiles.

## Abstract

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.

•Maternal 12-HETE levels associate with childhood asthma risk•Maternal 12-HETE levels relate to infant airway microbiota and immune patterns•Higher prenatal n-3 LCPUFA intake reduced childhood asthma risk in offspring•Effect of prenatal n-3 LCPUFA intake varies by maternal 12-HETE status

Maternal 12-HETE levels associate with childhood asthma risk

Maternal 12-HETE levels relate to infant airway microbiota and immune patterns

Higher prenatal n-3 LCPUFA intake reduced childhood asthma risk in offspring

Effect of prenatal n-3 LCPUFA intake varies by maternal 12-HETE status

Across two birth cohorts, Liang et al. found that maternal 12-HETE levels during pregnancy associate with childhood asthma and respiratory infections alongside altered infant airway microbiota and immune patterns. Effect of prenatal n-3 LCPUFA intake varies by maternal 12-HETE status, suggesting 12-HETE as a potential biomarker for precision prevention.

## Linked entities

- **Chemicals:** 12-HETE (PubChem CID 5283155)
- **Diseases:** asthma (MONDO:0004979), respiratory infections (MONDO:0024355)

## Full-text entities

- **Genes:** LPAR2 (lysophosphatidic acid receptor 2) [NCBI Gene 9170] {aka EDG-4, EDG4, LPA-2, LPA2}, CCL11 (C-C motif chemokine ligand 11) [NCBI Gene 6356] {aka SCYA11}, LOX (lysyl oxidase) [NCBI Gene 4015] {aka AAT10}, CXCL10 (C-X-C motif chemokine ligand 10) [NCBI Gene 3627] {aka C7, IFI10, INP10, IP-10, SCYB10, crg-2}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, IL13 (interleukin 13) [NCBI Gene 3596] {aka IL-13, P600}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, LTB4R (leukotriene B4 receptor) [NCBI Gene 1241] {aka BLT1, BLTR, CMKRL1, GPR16, LTB4R1, LTBR1}, RAPSN (receptor associated protein of the synapse) [NCBI Gene 5913] {aka CMS11, CMS4C, FADS, RAPSYN, RNF205}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, SCD (stearoyl-CoA desaturase) [NCBI Gene 6319] {aka FADS5, MSTP008, SCD1, SCDOS, hSCD1}, IL5 (interleukin 5) [NCBI Gene 3567] {aka EDF, IL-5, TRF}, ALOX15 (arachidonate 15-lipoxygenase) [NCBI Gene 246] {aka 12-LOX, 15-LOX, 15-LOX-1, LOG15}, PPARG (peroxisome proliferator activated receptor gamma) [NCBI Gene 5468] {aka CIMT1, FPLD3, GLM1, NR1C3, PPARG1, PPARG2}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, CCL22 (C-C motif chemokine ligand 22) [NCBI Gene 6367] {aka A-152E5.1, ABCD-1, DC/B-CK, MDC, SCYA22, STCP-1}, CCL26 (C-C motif chemokine ligand 26) [NCBI Gene 10344] {aka IMAC, MIP-4a, MIP-4alpha, SCYA26, TSC-1}, FFAR4 (free fatty acid receptor 4) [NCBI Gene 338557] {aka BMIQ10, GPR120, GPR129, GT01, O3FAR1, OB10Q}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, CCL4 (C-C motif chemokine ligand 4) [NCBI Gene 6351] {aka ACT2, AT744.1, G-26, HC21, LAG-1, LAG1}, LTB4R2 (leukotriene B4 receptor 2) [NCBI Gene 56413] {aka BLT2, BLTR2, JULF2, KPG_004, LTB4-R 2, LTB4-R2}, ALOX12 (arachidonate 12-lipoxygenase, 12S type) [NCBI Gene 239] {aka 12-LOX, 12S-LOX, LOG12}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CCL13 (C-C motif chemokine ligand 13) [NCBI Gene 6357] {aka CKb10, MCP-4, NCC-1, NCC1, SCYA13, SCYL1}, CCL17 (C-C motif chemokine ligand 17) [NCBI Gene 6361] {aka A-152E5.3, ABCD-2, SCYA17, TARC}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}
- **Diseases:** common cold (MESH:D003139), airflow obstruction (MESH:D029424), bronchitis (MESH:D001991), breathlessness (MESH:D004417), allergy (MESH:D004342), airway inflammation (MESH:D007249), fever (MESH:D005334), atopy (MESH:C564133), lipid (MESH:D011017), Asthma (MESH:D001249), respiratory disease (MESH:D012140), eczema (MESH:D004485), cough (MESH:D003371), croup (MESH:D003440), Persistent wheeze (MESH:D012135), atopic dermatitis (MESH:D003876), bacterial (MESH:D001424), Pneumonia (MESH:D011014), lung symptoms (MESH:D012818), acute tonsillitis (MESH:D014069), AMs (MESH:D055501), tachypnea (MESH:D059246), acute otitis media (MESH:D010033), allergic rhinitis (MESH:D065631), Lower respiratory tract infections (MESH:D012141), bronchiolitis (MESH:D001988), airway infections (MESH:D007239), VDAART (MESH:D014808)
- **Chemicals:** fructooligosaccharides (MESH:C116580), triacylglycerol (MESH:D014280), 15-HETE (MESH:C025984), lipid (MESH:D008055), Eicosanoid (MESH:D015777), EPA (MESH:D015118), vitamin D (MESH:D014807), 12-HETE (MESH:D019377), Prebiotics (MESH:D056692), 12-HHT (MESH:C008033), n-3 fatty acids (MESH:D015525), 5-HETE (MESH:C022022), LTB4 (MESH:D007975), olive oil (MESH:D000069463), 3-carboxy-4-methyl-5-propyl-2-furan propanoic acid (MESH:C468134), fish oil (MESH:D005395), Oxylipin (MESH:D054883), AA (MESH:D016718), DHA (MESH:D004281), HDoHEs (-)
- **Species:** Prevotella (genus) [taxon 838], Caryophanales (order) [taxon 1385], Streptococcus pneumoniae (species) [taxon 1313], Veillonella (genus) [taxon 29465], Bacilli (class) [taxon 91061], Rothia (genus) [taxon 508215], Homo sapiens (human, species) [taxon 9606], Gemella (genus) [taxon 1378], Lactobacillus (genus) [taxon 1578], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], gut metagenome (species) [taxon 749906], Haemophilus influenzae (species) [taxon 727], Mus musculus (house mouse, species) [taxon 10090], Moraxella catarrhalis (species) [taxon 480]

## Full text

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## Figures

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## References

69 references — full list in the complete paper: https://tomesphere.com/paper/PMC13006429/full.md

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Source: https://tomesphere.com/paper/PMC13006429