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Background <p>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.</p> Methods <p>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.</p> Results <p>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 (<i>n</i> = 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.</p> Conclusions <p>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.</p> <p></p>

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The association of newborn metabolites with early-life wheezing and asthma among US children in the ECHO Program

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  • 发表日期：

    2026年5月13日

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摘要

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.