Association between childhood cancer and prenatal exposure to ambient PM2.5 and NO2: a population-based cohort study in Canada

ABSTRACT Background Prenatal exposure to air pollution may be a risk factor for childhood cancer, but epidemiological evidence is scarce. Objective We investigated whether prenatal exposure to ambient fine particulate matter (PM 2.5 ) and nitrogen dioxide (NO 2 ) was associated with childhood cancer incidence. Methods We conducted a cohort study of 1,121,996 newborns in Quebec, Canada, from 2006-2020, with follow-up through 2023. Prenatal exposure was estimated at maternal residence using biweekly PM 2.5 and weekly NO 2 concentrations from satellite-based and land-use regression models, respectively. We estimated associations with any cancer, central nervous system (CNS) tumor and leukemia diagnosed before age 14 years using Cox proportional hazard models adjusted for potential confounders. We examined single- and two-pollutant models and assessed effect modification by maternal and child characteristics, including maternal comorbidity. Results The cohort included 2,187 incident cancer cases. Adjusted hazard ratios (HR) for any cancer were 1.08 (95% CI: 0.99-1.17) and 1.06 (95% CI: 0.98-1.15) per interquartile increase in PM 2.5 (2.4 μg/m 3 ) and NO 2 (4.8 μg/m 3 ). For CNS tumors, we found positive associations but only in children aged ≥7 years; the HR was 1.35 (95% CI: 0.98-1.88) for PM 2.5 and 1.36 (95% CI: 0.99-1.88) for NO 2 . Associations with acute lymphoblastic leukemia (ALL) were 1.06 (95% CI: 0.90-1.25) for PM 2.5 and 1.15 (95% CI: 0.98-1.37) for NO 2 . For acute myeloid leukemia (AML), a positive association was suggested for PM 2.5 (HR=1.15; 95% CI: 0.77-1.70), but the number of cases was low (n=95). Associations appeared greater among children whose mothers had comorbidities. Conclusion Prenatal exposure to ambient PM 2.5 and NO 2 may be associated with childhood cancer. Particularly, CNS tumors in children ≥7 years were associated with both pollutants, ALL with NO 2 , and AML showed suggestive associations with PM 2.5 . Maternal comorbidities may further increase risk, underscoring the need for large studies to confirm these findings and clarify underlying mechanisms.