Maternal exposure to ambient air pollution and risk of early childhood cancers: A population-based study in Ontario, Canada.

BACKGROUND There are increasing concerns regarding the role of exposure to ambient air pollution during pregnancy in the development of early childhood cancers. OBJECTIVE This population based study examined whether prenatal and early life (<1year of age) exposures to ambient air pollutants, including nitrogen dioxide (NO2) and particulate matter with aerodynamic diameters ≤2.5μm (PM2.5), were associated with selected common early childhood cancers in Canada. METHODS 2,350,898 singleton live births occurring between 1988 and 2012 were identified in the province of Ontario, Canada. We assigned temporally varying satellite-derived estimates of PM2.5 and land-use regression model estimates of NO2 to maternal residences during pregnancy. Incident cases of 13 subtypes of pediatric cancers among children up to age 6 until 2013 were ascertained through administrative health data linkages. Associations of trimester-specific, overall pregnancy and first year of life exposures were evaluated using Cox proportional hazards models, adjusting for potential confounders. RESULTS A total of 2044 childhood cancers were identified. Exposure to PM2.5, per interquartile range increase, over the entire pregnancy, and during the first trimester was associated with an increased risk of astrocytoma (hazard ratio (HR) per 3.9μg/m3=1.38 (95% CI: 1.01, 1.88) and, HR per 4.0μg/m3=1.40 (95% CI: 1.05-1.86), respectively). We also found a positive association between first trimester NO2 and acute lymphoblastic leukemia (ALL) (HR=1.20 (95% CI: 1.02-1.41) per IQR (13.3ppb)). CONCLUSIONS In this population-based study in the largest province of Canada, results suggest an association between exposure to ambient air pollution during pregnancy, especially in the first trimester and an increased risk of astrocytoma and ALL. Further studies are required to replicate the findings of this study with adjustment for important individual-level confounders.

[1]  Julia C. Fussell,et al.  Size, source and chemical composition as determinants of toxicity attributable to ambient particulate matter , 2012 .

[2]  S. Dunn,et al.  2008 Niday Perinatal Database quality audit: report of a quality assurance project. , 2011, Chronic diseases and injuries in Canada.

[3]  B. Ritz,et al.  An exploratory study of ambient air toxics exposure in pregnancy and the risk of neuroblastoma in offspring. , 2013, Environmental research.

[4]  A. Stewart Fotheringham,et al.  Geographically Weighted Regression: A Method for Exploring Spatial Nonstationarity , 2010 .

[5]  P. Villeneuve,et al.  Exposure to traffic-related air pollution and the risk of developing breast cancer among women in eight Canadian provinces: a case-control study. , 2015, Environment international.

[6]  J. Gurney Topical topics: Brain cancer incidence in children: time to look beyond the trends. , 1999, Medical and pediatric oncology.

[7]  B. Ritz,et al.  Prenatal exposure to traffic-related air pollution and risk of early childhood cancers. , 2013, American journal of epidemiology.

[8]  Todd E. Bodner,et al.  What Improves with Increased Missing Data Imputations? , 2008 .

[9]  Jarvis T. Chen,et al.  Comparing individual- and area-based socioeconomic measures for the surveillance of health disparities: A multilevel analysis of Massachusetts births, 1989-1991. , 2006, American journal of epidemiology.

[10]  S. Preston‐Martin,et al.  Epidemiology of brain tumors in childhood--a review. , 2004, Toxicology and applied pharmacology.

[11]  D. Hémon,et al.  Road Traffic and Childhood Leukemia: The ESCALE Study (SFCE) , 2010, Environmental health perspectives.

[12]  D. Postma,et al.  Epigenome-Wide Meta-Analysis of Methylation in Children Related to Prenatal NO2 Air Pollution Exposure , 2016, Environmental health perspectives.

[13]  Martyn T. Smith,et al.  Advances in understanding benzene health effects and susceptibility. , 2010, Annual review of public health.

[14]  Arthur T. DeGaetano,et al.  Temporal, spatial and meteorological variations in hourly PM2.5 concentration extremes in New York City , 2004 .

[15]  Alexander Kopp,et al.  Ambient Fine Particulate Matter and Mortality among Survivors of Myocardial Infarction: Population-Based Cohort Study , 2016, Environmental health perspectives.

[16]  M. Vinceti,et al.  A Review and Meta-Analysis of Outdoor Air Pollution and Risk of Childhood Leukemia , 2015, Journal of environmental science and health. Part C, Environmental carcinogenesis & ecotoxicology reviews.

[17]  Perry Hystad,et al.  Ambient air pollution and adverse birth outcomes: Differences by maternal comorbidities. , 2016, Environmental research.

[18]  F. Perera,et al.  PAH–DNA Adducts in Cord Blood and Fetal and Child Development in a Chinese Cohort , 2006, Environmental Health Perspectives.

[19]  C. Rossig,et al.  Aetiology of childhood acute leukaemias: current status of knowledge. , 2008, Radiation protection dosimetry.

[20]  L. Folinsbee Human health effects of air pollution. , 1993, Environmental health perspectives.

[21]  Jun Wu,et al.  Abstract 2531: Childhood cancer and traffic-related air pollution exposure in pregnancy and early life. , 2013 .

[22]  R. Cooney,et al.  Mutagenicity of nitric oxide and its inhibition by antioxidants. , 1992, Mutation research.

[23]  M. Brauer,et al.  Risk of Nonaccidental and Cardiovascular Mortality in Relation to Long-term Exposure to Low Concentrations of Fine Particulate Matter: A Canadian National-Level Cohort Study , 2012, Environmental health perspectives.

[24]  Arthur M. Wendel,et al.  Residential traffic exposure and childhood leukemia: a systematic review and meta-analysis. , 2014, American journal of preventive medicine.

[25]  Eva Steliarova-Foucher,et al.  International Classification of Childhood Cancer, third edition , 2005, Cancer.

[26]  Richard T Burnett,et al.  High-Resolution Satellite-Derived PM2.5 from Optimal Estimation and Geographically Weighted Regression over North America. , 2015, Environmental science & technology.

[27]  N. Jacobsen,et al.  Role of oxidative damage in toxicity of particulates , 2010, Free radical research.

[28]  C. Muir,et al.  International Classification of Diseases for Oncology , 1990 .

[29]  O. Raaschou-Nielsen,et al.  Air pollution and childhood cancer: A review of the epidemiological literature , 2006, International journal of cancer.

[30]  B. Ritz,et al.  Risk of leukemia in relation to exposure to ambient air toxics in pregnancy and early childhood. , 2014, International journal of hygiene and environmental health.

[31]  Shao Lin,et al.  Residential mobility during pregnancy and the potential for ambient air pollution exposure misclassification. , 2010, Environmental research.

[32]  Heather E. Danysh,et al.  Traffic‐related air pollution and the incidence of childhood central nervous system tumors: Texas, 2001–2009 , 2015, Pediatric blood & cancer.

[33]  B. Ritz,et al.  Prenatal Exposure to Air Toxics and Risk of Wilms' Tumor in 0- to 5-Year-Old Children , 2014, Journal of occupational and environmental medicine.

[34]  Luoping Zhang,et al.  Parental, In Utero, and Early-Life Exposure to Benzene and the Risk of Childhood Leukemia: A Meta-Analysis. , 2016, American journal of epidemiology.

[35]  D. Hémon,et al.  Residential Proximity to Heavy-Traffic Roads, Benzene Exposure, and Childhood Leukemia-The GEOCAP Study, 2002-2007. , 2015, American journal of epidemiology.

[36]  S. Preston‐Martin,et al.  Trends in childhood brain tumor incidence, 1973–2009 , 2013, Journal of Neuro-Oncology.

[37]  B. Ritz,et al.  In Utero and Early-Life Exposure to Ambient Air Toxics and Childhood Brain Tumors: A Population-Based Case–Control Study in California, USA , 2015, Environmental health perspectives.

[38]  A. Elder,et al.  Neurological impacts from inhalation of pollutants and the nose-brain connection. , 2012, Neurotoxicology.

[39]  Amanda E. Janitz,et al.  Traffic-related air pollution and childhood acute leukemia in Oklahoma. , 2016, Environmental research.

[40]  W. Teague,et al.  Outdoor air pollution. Asthma and other concerns. , 2001, Pediatric clinics of North America.

[41]  Patrick Royston,et al.  Multiple imputation using chained equations: Issues and guidance for practice , 2011, Statistics in medicine.

[42]  Peter C Austin,et al.  Estimating Multilevel Logistic Regression Models When the Number of Clusters is Low: A Comparison of Different Statistical Software Procedures , 2010, The international journal of biostatistics.

[43]  Timothy J. Robinson,et al.  Multilevel Analysis: Techniques and Applications , 2002 .

[44]  B. Ritz,et al.  Smoking in pregnancy and risk of cancer among young children: A population‐based study , 2016, International journal of cancer.

[45]  Michael Brauer,et al.  Within- and between-city contrasts in nitrogen dioxide and mortality in 10 Canadian cities; a subset of the Canadian Census Health and Environment Cohort (CanCHEC) , 2015, Journal of Exposure Science and Environmental Epidemiology.

[46]  J. Marshall,et al.  National Spatiotemporal Exposure Surface for NO2: Monthly Scaling of a Satellite-Derived Land-Use Regression, 2000-2010. , 2015, Environmental science & technology.

[47]  Michael Tjepkema,et al.  A national study of the association between traffic-related air pollution and adverse pregnancy outcomes in Canada, 1999-2008. , 2016, Environmental research.

[48]  Mark L. Greenberg,et al.  Childhood cancer registries in Ontario, Canada: Lessons learned from a comparison of two registries , 2003, International journal of cancer.

[49]  M. Brauer,et al.  Creating National Air Pollution Models for Population Exposure Assessment in Canada , 2011, Environmental health perspectives.

[50]  B. Ritz,et al.  Retinoblastoma and ambient exposure to air toxics in the perinatal period , 2013, Journal of Exposure Science and Environmental Epidemiology.

[51]  J. Graham,et al.  How Many Imputations are Really Needed? Some Practical Clarifications of Multiple Imputation Theory , 2007, Prevention Science.

[52]  John B Carlin,et al.  American Journal of Epidemiology Practice of Epidemiology Strategies for Multiple Imputation in Longitudinal Studies , 2022 .

[53]  Xiaoling Ma,et al.  No association between traffic density and risk of childhood leukemia: a meta-analysis. , 2014, Asian Pacific journal of cancer prevention : APJCP.

[54]  April Fritz,et al.  International Classification of Diseases for Oncology: ICD-0. , 2000 .

[55]  P. Kaatsch Epidemiology of childhood cancer. , 2010, Cancer treatment reviews.

[56]  Joseph P. Pinto,et al.  Ground-level nitrogen dioxide concentrations inferred from the satellite-borne Ozone Monitoring Instrument , 2008 .

[57]  Wenyaw Chan,et al.  Differences in exposure assignment between conception and delivery: the impact of maternal mobility. , 2010, Paediatric and perinatal epidemiology.

[58]  K. Appel,et al.  Niltrogen dioxide induces DNA single-strand breaks in cultured Chinese hamster cells , 1990 .

[59]  M. Greaves Science, medicine, and the future: Childhood leukaemia , 2002 .

[60]  P. Buffler,et al.  Factors associated with residential mobility in children with leukemia: implications for assigning exposures. , 2009, Annals of epidemiology.