This Canadian cohort study enrolled 3,454 healthy children and their families from early pregnancy and followed them until age 5. The investigators assessed 2,954 diverse early-life exposures spanning pregnancy through early childhood and examined associations with childhood asthma. Secondary outcomes included epigenetic changes in cord blood, microbiome changes, and inflammatory cytokine changes.
The study reported significant associations between childhood asthma and several exposures: antibiotic use, human milk components, DEHP phthalate, and mothers' prenatal cleaning product and disinfectant exposure. The study did not report effect sizes, absolute numbers, p-values, or confidence intervals for these associations.
Safety and tolerability data were not reported, as this observational exposure assessment did not involve a therapeutic intervention. The authors note that integrating diverse data types is required to address association confounders. The study supports the concept that asthma is a heterogeneous condition involving multiple etiologies and suggests targets for early interventions.
These findings should be interpreted cautiously. Without quantitative effect measures, the strength and precision of the associations are unknown. The observational design cannot establish causation, and unmeasured confounding may influence results. Clinicians can consider these exposures as part of a multifactorial risk landscape while avoiding causal interpretations.
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Identification of early interventions to reduce/eliminate asthma - the most common chronic disease among children - could significantly reduce burden on the healthcare system. Large-scale asthma Exposome-Wide Association Studies (ExWAS) could identify potential interventions, however integration of diverse data is required to address association confounders. The CHILD Cohort Study has followed 3,454 healthy Canadian children and their families from early pregnancy, collecting exceptionally diverse data including 24,852 variables from participant questionnaires, clinical data, household and neighbourhood-level exposures, and sample-derived chemical analytic/omic datasets. Here, we report integration of these datasets into the CHILDdb database platform, and use these data to perform ExWAS and machine learning analyses, identifying and further characterizing associations between childhood asthma and 2,954 diverse early exposures (pregnancy to age 5). Significant asthma associations include antibiotic use, human milk components, DEHP phthalate, and mothers prenatal cleaning product/disinfectant exposure. Subsequent analysis revealed epigenetic changes in the cord blood at birth, after prenatal cleaner exposure, and different microbiome and/or inflammatory cytokine changes associated with different asthma-associated exposures in the child. Collective results support asthma as a heterogeneous condition involving multiple etiologies, with associated endotypes, including prenatal exposures with potential transgenerational effects, and suggest targets for early interventions.