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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. [ABSTRACT FROM AUTHOR]

Background: Early exposure to allergens through a defect skin barrier has been proposed as a mechanism for inducing sensitization and development of allergic diseases. We hypothesized that early‐onset, severe atopic dermatitis (AD) is associated with development of aeroallergen sensitization and allergic rhinitis. Methods: We included 368 children from the Copenhagen Prospective Studies on Asthma in Childhood2000 (COPSAC2000) at‐risk mother‐child cohort. AD was diagnosed prospectively based on Hanifin&Rajka's criteria and severity assessed using the Scoring Atopic Dermatitis (SCORAD) index. Early‐onset AD was defined as debut ≤1 year, late‐onset as debut from 1–6 years. Aeroallergen sensitization and allergic rhinitis were diagnosed at ages 6–7 and 12 years. Associations between early‐onset and late‐onset AD and allergy endpoints were calculated using general estimating equations (GEE) models to compute the overall odds ratios (OR) for both time points. Results: Early‐onset AD (yes/no) and severity (SCORAD) were associated with development of aeroallergen sensitization during childhood; GEE OR = 1.68 [1.08; 2.62], p =.02 and 1.08 [1.03; 1.12], p <.001, whereas late‐onset AD showed a borderline significant association and late‐onset severity showed no association; GEE OR = 1.65 [0.92; 2.94], p =.08 and 1.01 [0.97; 1.06], p =.55. The same trend was seen for allergic rhinitis with significant association between early‐onset AD and allergic rhinitis; GEE OR = 1.56 [1.01; 2.41], p =.04 and severity; GEE OR = 1.09 [1.05; 1.13], p <.001, whereas late‐onset AD showed no association. The effects on sensitization and rhinitis of early‐onset versus late‐onset AD severity were significantly different: p‐interactionsensitization =.03 and p‐interactionrhinitis <.01. Conclusion: Increasing severity of early‐onset AD, but not late‐onset AD, associates with aeroallergen sensitization and allergic rhinitis later in childhood. [ABSTRACT FROM AUTHOR]

Background: Asthma‐like symptoms in young children are orchestrated by the local airway immune response, but current knowledge largely relies on in vitro airway models. Azithromycin has been shown to reduce the duration of episodes with asthma‐like symptoms, but efficacy may depend on the individual child's immune response. Objectives: To investigate in vivo upper airway immune mediator levels during episodes with asthma‐like symptoms in young children and their ability to predict the clinical response to azithromycin treatment. Methods: A total of 535 children aged 0‐3 years from the Copenhagen Prospective Studies of Asthma in Childhood‐2010 mother‐child cohort were examined for immune mediator levels in samples of nasal epithelial lining fluid during episodes with asthma‐like symptoms as well as in the asymptomatic state. In a sub‐study, children with recurrent asthma‐like symptoms were randomized to either a 3‐day course of oral azithromycin (10 mg/kg; n = 32) or placebo (n = 38). In the current study, we compared the pretreatment immune mediator levels with the clinical response to treatment with azithromycin in an exploratory post hoc analysis. Results: The immune mediator concentrations during vs outside episodes were significantly upregulated for IFN‐ɣ (ratio 1.73), TNF‐α (ratio 2.05), IL‐1β (ratio 1.45), IL‐10 (ratio 1.97), while CCL22 (ratio 0.65) was downregulated. Low levels of TNF‐α and IL‐10 and high levels of CCL22 predicted better treatment response to azithromycin (P‐values <.05). Conclusion: Upper airway immune mediator levels were altered during episodes of asthma‐like symptoms, and levels of TNF‐α, CCL22, and IL‐10 may predict the response to azithromycin treatment. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Infantile colic is a common condition with limited knowledge about later clinical manifestations. We evaluated the role of the early life gut microbiome in infantile colic and later development of atopic and gastrointestinal disorders.Copenhagen Prospective Studies on Asthma in Childhood2010 cohort was followed with 6 years of extensive clinical phenotyping. The 1‐month gut microbiome was analyzed by 16S rRNA sequencing. Infantile colic was evaluated at age 3 months by interviews. Clinical endpoints included constipation to age 3 years and prospectively diagnosed asthma and atopic dermatitis in the first 6 years of life, and allergic sensitization from skin prick tests, specific Immunoglobulin E, and component analyses.Of 695 children, 55 children (7.9%) had infantile colic. Several factors were associated with colic including race, breastfeeding, and pets. The 1‐month gut microbiome composition and taxa abundances were not associated with colic, however a sparse Partial Least Squares model including combined abundances of nine species was moderately predictive of colic: median, cross‐validated AUC = 0.627, p = .003. Children with infantile colic had an increased risk of developing constipation (aOR, 2.88 [1.51–5.35], p = .001) later in life, but also asthma (aHR, 1.69 [1.02–2.79], p = .040), atopic dermatitis (aHR, 1.84 [1.20–2.81], p = .005) and had a higher number of positive allergic components (adjusted difference, 116% [14%–280%], p = .012) in the first 6 years. These associations were not mediated by gut microbiome differences.We link infantile colic with risk of developing constipation and atopic disorders in the first 6 years of life, which was not mediated through an altered gut microbiome at age 1‐month. These results suggest infantile colic to involve gastrointestinal and/or atopic mechanisms. [ABSTRACT FROM AUTHOR]