Kawasaki disease and prenatal exposure to air pollution: A population-based cohort study

Abstract

Background/Aim: Kawasaki disease (KD) is the leading cause of acquired heart disease in children in North America. Causes of KD remain to be elucidated. Environmental factors may play an etiologic role but prenatal environmental exposures are understudied. We investigated whether prenatal exposure to outdoor air pollution is associated with the incidence of KD in childhood. Methods: We used an open birth cohort derived from health administrative databases. Children born in the province of Quebec (Canada) between 2006-2012 were followed up until March 31, 2018. Incident diagnoses of KD were ascertained from health administrative data. We assigned prenatal exposures using annual average concentrations at the residential postal code at birth. Pollutants investigated were ambient fine particulate matter (PM2.5), nitrogen dioxide (NO2) and sulfur dioxide (SO2) from industrial emissions estimated from dispersion modeling, as well as regional PM2.5 and traffic-related NO2 estimated from satellite-based and land-use regression models. We assessed associations between prenatal air pollutant exposure and incident KD using Cox proportional hazards models, adjusting for individual and contextual factors. Sensitivity analyses included modifying effects of maternal comorbidities (i.e., obesity, diabetes and preeclampsia). Results: The cohort comprised 505,336 children, including 539 incident cases of KD. Adjusted hazard ratios (HRs) per interquartile range increase in industrial air pollution were 1.07 (95% CI: 1.01, 1.13) for SO2, 1.09 (95% CI: 0.99, 1.20) for NO2, and 1.01 (95% CI: 0.97, 1.05) for PM2.5. Association for industrial SO2 strengthened (HR = 1.23; 95% CI: 1.06, 1.42) upon adjustment for industrial NO2 and PM2.5. For regional PM2.5 and traffic-related NO2, HRs were 1.16 (95% CI: 0.96, 1.39) and 1.12 (95% CI: 0.96, 1.31). Associations for NO2 appeared enhanced by maternal diabetes. Conclusions: This population-based cohort study supports a possible link between KD and prenatal exposure to air pollution. Further studies are needed to consolidate these findings.