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

Undetectable maternal plasma 12-HETE during pregnancy was associated with increased risk of childhood asthma in the COPSAC2010 cohort.

• Data were drawn from the COPSAC2010 mother-child cohort and replicated in VDAART.
• Maternal 12-HETE was measured in plasma samples collected during pregnancy.
• Undetectable 12-HETE levels (below the limit of detection) defined the low-exposure group.
• The association was observed for childhood asthma as an outcome across both cohorts.

Undetectable maternal plasma 12-HETE during pregnancy was associated with increased risk of childhood respiratory infections.

• This finding was observed in both COPSAC2010 and VDAART cohorts.
• Respiratory infections were assessed as a separate outcome from asthma.
• The finding extended the mouse study evidence of 12-HETE deficiency and respiratory morbidity to a human population.

Undetectable maternal 12-HETE was associated with an altered infant airway microbiota structure.

• Airway microbiota was assessed in infants from the COPSAC2010 cohort.
• Maternal 12-HETE status during pregnancy was linked to differences in infant airway microbial community composition.
• This represents a potential biological mechanism linking maternal 12-HETE to offspring respiratory outcomes.

Undetectable maternal 12-HETE was associated with an altered infant airway immune profile.

• Airway immune profiling was conducted in infants from COPSAC2010.
• Differences in the airway immune profile were observed according to maternal 12-HETE detection status.
• This immune alteration may contribute to the increased respiratory morbidity observed in offspring of mothers with undetectable 12-HETE.

An interaction was observed between maternal 12-HETE levels and prenatal n-3 LCPUFA exposure in relation to offspring respiratory morbidity.

• In COPSAC2010, the interaction was assessed using a randomized clinical trial of maternal n-3 LCPUFA supplementation.
• In VDAART, the interaction was assessed using maternal dietary n-3 LCPUFA intake.
• Higher prenatal n-3 LCPUFA exposure reduced asthma and respiratory infections specifically among mothers with detectable 12-HETE levels.
• Among mothers with undetectable 12-HETE, the protective effect of n-3 LCPUFA supplementation was not observed.
• This interaction was replicated across two independent cohorts using different measures of n-3 LCPUFA exposure.

Maternal 12-HETE deficiency affects neonatal alveolar macrophage imprinting in mice, providing biological context for the human findings.

• This was established in a prior mouse study referenced by the authors.
• 12-HETE deficiency in mice was associated with increased respiratory morbidity.
• The current study represents the first investigation of this mechanism in humans.
• Mouse findings motivated examination of maternal 12-HETE as a potential biomarker in human cohorts.

Maternal 12-HETE is identified as a potential biomarker for risk of offspring respiratory morbidity.

• Findings were consistent across two independent mother-child cohorts (COPSAC2010 and VDAART).
• Maternal 12-HETE status during pregnancy predicted childhood asthma and respiratory infections.
• The authors suggest maternal 12-HETE status may determine responsiveness to prenatal n-3 LCPUFA supplementation.
• This positions 12-HETE as a candidate stratification biomarker for prenatal intervention trials.