Association between Kawasaki Disease and Prenatal Exposure to Ambient and Industrial Air Pollution: A Population-Based Cohort Study

Abstract

Background: Environmental factors may contribute to the development of Kawasaki disease in children, but prenatal environmental exposures are understudied.

Objective: We used a population-based cohort to investigate whether prenatal exposure to outdoor air pollution is associated with the incidence of Kawasaki disease in childhood.

Methods: We performed a longitudinal cohort study of all children born in Quebec, Canada, between 2006 and 2012. Children were followed for Kawasaki disease from birth until 31 March 2018. We assigned prenatal air pollutant exposure according to the residential postal code at birth. The main exposure was annual average concentration of ambient fine particulate matter [PM $\le 2.5\mu m$ in aerodynamic diameter (${\mathrm{PM}}_{2.5}$) and nitrogen dioxide (${\mathrm{NO}}_2$) from satellite-based estimates and land-use regression models. As secondary exposures, we considered industrial ${\mathrm{PM}}_{2.5}$, ${\mathrm{NO}}_2$, and sulfur dioxide (${\mathrm{SO}}_2$) emissions estimated from dispersion models. We estimated hazard ratios (HRs) using Cox proportional hazards models, adjusted for maternal age, parity, sex, multiple birth, maternal smoking during pregnancy, socioeconomic status, birth year, and rural residence. We considered single and multipollutant models. We performed several sensitivity analyses, including assessing modifying effects of maternal comorbidities (e.g., diabetes, preeclampsia).

Results: The cohort comprised 505,336 children, including 539 with Kawasaki disease. HRs for each interquartile range increase in ambient air pollution were 1.16 (95% CI: 0.96, 1.39) for ${\mathrm{PM}}_{2.5}$ and 1.12 (95% CI: 0.96, 1.31) for ${\mathrm{NO}}_2$. For industrial air pollution, HRs were 1.07 (95% CI: 1.01, 1.13) for ${\mathrm{SO}}_2$, 1.09 (95% CI: 0.99, 1.20) for ${\mathrm{NO}}_2$, and 1.01 (95% CI: 0.97, 1.05) for ${\mathrm{PM}}_{2.5}$. In multipollutant models, associations for ambient ${\mathrm{PM}}_{2.5}$ and ${\mathrm{NO}}_2$ (i.e., from all sources) were robust to adjustment for industrial pollution, and vice versa.

Discussion: In this population-based cohort study, both prenatal exposure to ambient and industrial air pollution were associated with the incidence of Kawasaki disease in childhood. Further studies are needed to consolidate the observed associations. https://doi.org/10.1289/EHP6920.