The impact of prematurity on pediatric asthma morbidity and indices with environmental pollution and genetic susceptibility.

Background: Prematurity, fine particulate matter (PM_2.5), and genetic variables are linked to asthma incidence in children. However, to capture the contributions of these variables and their involvement in asthma pathogenesis, we need to understand how they interact. Here, we aim to assess the impact of prematurity on asthma exacerbations and explore interactions with PM_2.5 exposure and genetic risk.

Methods: Pediatric patients with asthma and at least 5 years of follow-up data were identified from the Center for Applied Genomics biobank. Subjects were classified as full term (FT), late preterm (LPT), or extremely/very preterm (E/VPT). PM_2.5 exposure was calculated as the proportion of days between diagnosis and last recorded follow up exceeding 8 µg/m³, and a polygenic risk score (sPRS) was used to assess genetic PM_2.5 susceptibility. Regression models evaluated predictors of asthma exacerbations.

Results: Among 5982 patients, 16% are LPT and 4% E/VPT. The latter patient group experiences 20.5% more exacerbations than FT patients (P = 0.04). E/VPT patients have 43.3% more exacerbations per unit increase in PM_2.5 exposure (P = 0.001) and LPT patients with a high sPRS experienced 24.0% more exacerbations (P = 0.04) compared to what would be expected from the sum of the independent effects. Additionally, LPT and E/VPT patients have 24% (P = 0.012) and 61% (P = 0.005) higher odds of exacerbations beyond 6 years of age, respectively.

Conclusions: Interactions between prematurity, PM_2.5 exposure, and genetic susceptibility exacerbate asthma morbidity, underscoring the urgent need for targeted interventions in high-risk populations with overlapping vulnerabilities.