Protocols

Environmental exposures were assessed in pregnancy and childhood stages. A total of 25 families of exposures were assessed in each mother-child pair, with 69 pregnancy and 129 childhood exposures (total of 198 exposures). Exposure assessment tools included mass-spectrometry based measurement of biomarkers of chemical exposure in urine and blood, exposure monitors, remote sensing and geospatial methods, and questionnaire-based interviews.

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The study investigated 11 preclinical and clinical health outcomes in four key health areas linked to non-communicable disease risk and prevalent among European children. These outcomes were assessed consistently during childhood and adolescence, enabling a longitudinal analysis of exposome-health associations across 22 outcome variables. The health domains studied were:

1. Mental Health (3 variables): Internalizing and externalizing symptoms were assessed using neuropsychological tools like the Child Behavior Checklist (CBCL) and the Conner’s ADHD index.
2. Cardiometabolic Health (3 variables): Included age- and sex-standardized BMI z-scores (z-BMI) based on WHO curves, and systolic and diastolic blood pressure assessed using standardized protocols.
3. Respiratory Health (3 variables): Focused on respiratory symptoms (wheeze) and clinical conditions such as doctor-diagnosed asthma and asthma medication use.
4. Immune Health (2 variables): Examined outcomes related to allergies, including eczema and rhinitis.

We systematically tested the association between each exposure variable and each health outcome following the traditional Exposome-Wide Association Analysis (ExWAS) approach by fitting linear regression adjusted models for each exposure-outcome pair (for more details regarding confounders, please, visit our article.
(Reference not yet available, article under review)

Additionally, we employed an innovative Outcome-Wide Exposome Association Analysis approach, to jointly estimate prospective associations between a broad spectrum of 198 prenatal and childhood environmental exposures and the 11 health outcomes assessed at two developmental stages.