AbstractBackgroundIntake of fish‐oil and fatty fish during pregnancy has been shown to reduce the risk of childhood asthma but biomarkers of such intake are lacking.ObjectiveTo establish biomarkers of prenatal fish‐oil exposure from newborn dry blood spot metabolomics profiles and assess their relevance for childhood asthma risk stratification.MethodsThe Danish COPSAC₂₀₁₀ mother–child cohort was utilized to investigate the effect of a double‐blinded randomized controlled trial of fish‐oil supplementation during pregnancy on dry blood spot liquid‐chromatography mass spectrometry‐based metabolomics profiles of 677 newborns. We thereafter investigated the association between fish‐oil associated biomarkers in the newborn and development of asthma‐related outcomes. Replication was sought in the independent observational COPSAC₂₀₀₀ cohort with 387 newborn metabolomics profiles.ResultsThe newborn metabolomics profiles differed between children in the fish‐oil vs. placebo group in COPSAC₂₀₁₀ (area under the receiver operator curve = 0.94 ± 0.03, p < .001). The fish‐oil metabolomics profile and the top biomarker, 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furan propanoic acid (CMPF) were both associated with a decreased risk of asthma by age 6 years (HR = 0.89, p = .002 and HR = 0.67, p = .005, respectively). In COPSAC₂₀₀₀, newborn CMPF level was also inversely associated with asthma risk by age 6 years (HR = 0.69, p = .01). Troublesome lung symptoms and common infections in the first 3 years were also inversely associated with newborn CMPF levels in both cohorts.ConclusionsNewborn children's blood levels of the furan fatty acid metabolite CMPF reflect fish‐oil and fatty fish intake during pregnancy and are associated with a lower risk of asthma across two cohorts, which could aid newborn screening for childhood asthma.