Long-term PM2.5 exposure and leukemia risk from childhood to early adulthood: A nationwide longitudinal cohort study with time-varying exposure analysis.

Abstract

Long-term exposure to fine particulate matter (PM2.5) has been suggested as an environmental risk factor for childhood leukemia. This study examined the association between time-varying PM2.5 exposure and leukemia incidence in a nationwide cohort of Korean children and adolescents. We used data from the National Health Insurance Service-National Sample Cohort (2002-2020), including beneficiaries aged 0-18 years at enrollment who were followed until leukemia onset, death, or study end. Leukemia onset was defined as the first hospital visit with a primary diagnostic code from the 10th revision of the International Classification of Diseases. Annual PM2.5 concentrations were assigned to all 226 inland districts in South Korea using mean predictions from a machine learning-based ensemble model. Cox regression models with time-varying exposures and confounders were applied. Two-pollutant models incorporating NO2 and O3 were conducted as sensitivity analyses. Among 384,606 individuals aged 0-18 at enrollment, 272 developed leukemia during follow-up, including 83 who were diagnosed after the age of 18 years. The cohort's average annual PM2.5 concentration was 29.6 μg/m3 (standard deviation: 3.1). Each 5 μg/m3 increase in annual PM2.5 was associated with a hazard ratio of 1.40 (95% confidence interval: 1.04-1.90) for leukemia. The effect estimate remained comparable when follow-up was censored at age 18 years, suggesting that the findings were not materially influenced by the inclusion of diagnoses occurring after age 18. Long-term PM2.5 exposure was associated with increased leukemia incidence in this national cohort. These findings underscore the importance of reducing air pollution to protect the health of children and adolescents.