Early Respiratory Infection Burden and Atopic Dermatitis in Childhood.

Abstract

The exposome has been proposed to have a key role in the development of atopic dermatitis (AD). However, whether early-life infections are associated with AD risk remains unclear. To investigate whether early infection burden and infection subtypes are associated with the risk of childhood AD. A cohort study using data from children aged 0 to 10 years from the 2010 Danish Copenhagen Prospective Studies on Asthma in Childhood (COPSAC2010) birth cohort who were monitored for infection diagnoses, AD diagnosis, Scoring Atopic Dermatitis (SCORAD) index score, systemic antibiotics, and filaggrin gene (FLG) status. Replication was sought in a second birth cohort from the US Vitamin D Antenatal Asthma Reduction Trial (VDAART) cohort. Data were analyzed between January and February 2026. Daily diary-registered infection episodes of cold, acute otitis media, tonsillitis, pneumonia, gastroenteritis, and fever episodes and days until age 3 years in COPSAC2010. Cold, fever, respiratory infection, and fever episodes until age 3 years in VDAART. Risk of AD during age 0 to 10 years using diagnostic criteria with longitudinal risk assessment from a generalized estimating equation (GEE) model in COPSAC2010. Analyses adjusted for FLG variant and systemic antibiotic treatments. Parental report of physician AD diagnosis until age 6 years was used in VDAART. Among 663 children in COPSAC2010, children in the upper (n = 221; 112 males [51%], 109 females [49%]) vs lower (n = 221; 109 males [49%], 112 females [51%]) tertiles of infection episodes and days were associated with higher risk of yearly AD prevalence during ages 0 to 10 years (GEE model): adjusted odds ratio (AOR), 1.61; 95% CI, 1.05-2.47; P = .03; and AOR, 1.69; 95% CI, 1.11-2.58; P = .01, respectively. Each infection episode was associated with a higher AD risk as well, independently of systemic antibiotic treatments and FLG variants. Associations were mainly driven by respiratory infections. In VDAART (n = 707), children in the upper (n = 235; 125 males [53%], 110 females [47%]) vs lower (n = 236; 119 males [50%], 117 females [50%]) tertiles of infection episodes were associated with a higher risk of AD at ages 0 to 6 years (OR, 1.76; 95% CI, 1.16-2.70; P = .01), increasing by each infection episode (OR, 1.03; 95% CI, 1.01-1.05; P = .002). This study found that early respiratory infection burden is associated with AD diagnosis in a dose-dependent manner in 2 independent birth cohorts. These findings suggest a long-term relationship between early respiratory infections and AD that has previously been unclear due to inconsistent findings in previous studies.