Cell Rep Med
Could maternal fatty acids predict childhood asthma risk?
Clinical Takeaway: This fatty acid, 12-HETE, may emerge as a biomarker to identify pregnant women whose infants would benefit most from omega-3 supplementation, perhaps leading to a more personalized approach to asthma prevention.
When a specific lipid molecule was undetectable in a pregnant woman's blood, her child faced a significantly higher risk of developing asthma and respiratory infections. Omega-3 supplementation during pregnancy only helped when the molecule was present.
The molecule, 12-hydroxyeicosatetraenoic acid (12-HETE), was undetectable in some pregnant women's blood at week 24 of gestation. Children born to those women had a 62% higher risk of developing asthma over the first ten years of life compared with children whose mothers had measurable 12-HETE levels. They also had more respiratory infections in the first three years of life.
The omega-3 finding added another layer. In a randomized trial within a Danish cohort, prenatal omega-3 supplementation reduced childhood asthma risk by 58%, but only among mothers with detectable 12-HETE. Among mothers without measurable levels, supplementation showed no benefit. The pattern held in the American validation cohort using dietary omega-3 intake.
The body makes 12-HETE from arachidonic acid, an omega-6 fat found in meat, eggs, and dairy, using specific enzymes. That means diet can influence how much raw material is available, but whether the body actually converts it into 12-HETE depends on individual enzyme activity, which varies from person to person and isn't fully understood.
Women with undetectable 12-HETE likely have insufficient enzyme activity to convert arachidonic acid into 12-HETE, regardless of how much substrate is available from diet. 12-HETE is made from omega-6 fatty acids, while omega-3s work through a separate anti-inflammatory pathway involving macrophages. The two are biologically distinct but appear to work together.
The current hypothesis is that 12-HETE establishes the immune foundation in the infant lung early in development, and omega-3 supplementation can only enhance that foundation if 12-HETE was present to build it in the first place.
Mechanistic data also pointed to a possible explanation. Infants of mothers with undetectable 12-HETE had altered airway bacterial composition as early as one week after birth, with higher relative abundance of bacteria previously linked to asthma risk. They also showed a distinct airway immune profile at one month of age, characterized by markers of heightened early inflammation and reduced regulatory signals. This is a pattern that partly mediated the association with later asthma.
Researchers drew on two prospective mother-child cohorts: a Danish (738 mothers, 700 children, followed to age 10) and an American cohort (881 mothers, 810 children, followed to age 6). Maternal plasma was analyzed for 12-HETE at mid-pregnancy using untargeted metabolomics.
The findings suggest 12-HETE may play a role in early immune and airway microbiome development, possibly through its effects on alveolar macrophage maturation, though direct evidence in infants is needed. If validated, measuring 12-HETE in pregnancy could help identify women most likely to benefit from targeted omega-3 supplementation.
"We show that 12-HETE is crucial for whether omega-3 supplementation during pregnancy has a protective effect against childhood asthma. In other words, it is not certain that all pregnant women will benefit from the same supplements, but in the future, we may be able to identify those who will gain the greatest benefit," said Bo Chawes, MD, PhD, clinical professor at the University of Copenhagen and Copenhagen Prospective Studies on Asthma in Childhood.
Source: Chen L, et al. Cell Rep Med. 2026 Mar 17. Maternal 12-HETE is associated with childhood asthma and the responses to prenatal omega-3 supplementation