Communications medicine · 2026
The association of newborn metabolites with early-life wheezing and asthma among US children in the ECHO Program.
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Snyder Brittney M, Gebretsadik Tebeb, Dupont William D, McKennan Christopher G, Ober Carole, Gern James E, Dabelea Dana M, Hartert Tina V, ECHO Cohort Consortium
Аннотация
BACKGROUND: We aimed to investigate associations between newborn metabolite concentrations and the development of early-life wheezing and asthma. Our goal was to advance understanding of pathways involved in childhood asthma pathogenesis and identify potential targets for disease prevention.
METHODS: Our study populations included children enrolled in two Environmental influences on Child Health Outcomes (ECHO) cohorts (INSPIRE, discovery; Healthy Start, replication) with linked newborn screening metabolic and outcome data (4-year recurrent wheeze and 5-year current asthma). We used elastic net penalized regression, followed by multivariable logistic regression, to determine metabolite-wheeze and metabolite-asthma associations. We secondarily assessed whether metabolite-asthma associations differed by asthma phenotype in the discovery cohort.
RESULTS: Among 1554 INSPIRE children, the prevalence of recurrent wheeze and current asthma is 11% and 18%, respectively. Newborn concentrations of butyrylcarnitine + isobutyrylcarnitine (C4) and decenoylcarnitine (C10:1) are associated with recurrent wheeze (C4: aOR 0.75 [95% CI 0.59, 0.95]; C10:1: aOR 1.42 [95% CI 1.13, 1.78]), while linoleoylcarnitine (C18:2) and citrulline (CIT) are associated with current asthma (C18:2: aOR 1.20 [95% CI 1.02, 1.41]; CIT: aOR 0.74 [95% CI 0.58, 0.93]). The effect size and directionality of the association between C18:2 and childhood asthma is similar in Healthy Start (n = 518), although the relationship is not statistically significant. C18:2 is additionally associated with increased odds of non-allergic asthma compared to no asthma in INSPIRE.
CONCLUSIONS: These findings suggest biologic pathways that may be involved in childhood asthma pathogenesis and support investigation of the mechanisms underlying these relationships given the potential for targeted prevention strategies.
METHODS: Our study populations included children enrolled in two Environmental influences on Child Health Outcomes (ECHO) cohorts (INSPIRE, discovery; Healthy Start, replication) with linked newborn screening metabolic and outcome data (4-year recurrent wheeze and 5-year current asthma). We used elastic net penalized regression, followed by multivariable logistic regression, to determine metabolite-wheeze and metabolite-asthma associations. We secondarily assessed whether metabolite-asthma associations differed by asthma phenotype in the discovery cohort.
RESULTS: Among 1554 INSPIRE children, the prevalence of recurrent wheeze and current asthma is 11% and 18%, respectively. Newborn concentrations of butyrylcarnitine + isobutyrylcarnitine (C4) and decenoylcarnitine (C10:1) are associated with recurrent wheeze (C4: aOR 0.75 [95% CI 0.59, 0.95]; C10:1: aOR 1.42 [95% CI 1.13, 1.78]), while linoleoylcarnitine (C18:2) and citrulline (CIT) are associated with current asthma (C18:2: aOR 1.20 [95% CI 1.02, 1.41]; CIT: aOR 0.74 [95% CI 0.58, 0.93]). The effect size and directionality of the association between C18:2 and childhood asthma is similar in Healthy Start (n = 518), although the relationship is not statistically significant. C18:2 is additionally associated with increased odds of non-allergic asthma compared to no asthma in INSPIRE.
CONCLUSIONS: These findings suggest biologic pathways that may be involved in childhood asthma pathogenesis and support investigation of the mechanisms underlying these relationships given the potential for targeted prevention strategies.