Background: Intake 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. 

Objective: To establish biomarkers of prenatal fish-oil exposure from newborn dry blood spot metabolomics profiles and assess their relevance for childhood asthma risk stratification. 

Methods: The 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. 

Results: The 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.

Conclusions: Newborn 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.