Abstract
Lead, mercury, and arsenic are neurotoxicants with known effects on neurodevelopment. Autism spectrum disorder (ASD) is a neurodevelopmental disorder apparent by early childhood. Using data on 4486 children with ASD residing in 2489 census tracts in five sites of the Centers for Disease Control and Prevention’s Autism and Developmental Disabilities Monitoring (ADDM) Network, we used multi-level negative binomial models to investigate if ambient lead, mercury, and arsenic concentrations, as measured by the US Environmental Protection Agency National-Scale Air Toxics Assessment (EPA-NATA), were associated with ASD prevalence. In unadjusted analyses, ambient metal concentrations were negatively associated with ASD prevalence. After adjusting for confounding factors, tracts with air concentrations of lead in the highest quartile had significantly higher ASD prevalence than tracts with lead concentrations in the lowest quartile (prevalence ratio (PR) = 1.36; 95 '% CI: 1.18, 1.57). In addition, tracts with mercury concentrations above the 75th percentile (>1.7 ng/m3) and arsenic concentrations below the 75th percentile (≤0.13 ng/m3) had a significantly higher ASD prevalence (adjusted RR = 1.20; 95 % CI: 1.03, 1.40) compared to tracts with arsenic, lead, and mercury concentrations below the 75th percentile. Our results suggest a possible association between ambient lead concentrations and ASD prevalence and demonstrate that exposure to multiple metals may have synergistic effects on ASD prevalence.
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Adams, J. B., Audhya, T., McDonough-Means, S., Rubin, R. A., Quig, D., Geis, E., et al. (2013). Toxicological status of children with autism vs. neurotypical children and the association with autism severity. Biological Trace Element Research, 151(2), 171–180. doi:10.1007/s12011-012-9551-1.
Adams, J. B., Holloway, C. E., George, F., & Quig, D. (2006). Analyses of toxic metals and essential minerals in the hair of Arizona children with autism and associated conditions, and their mothers. Biological Trace Element Research, 110(3), 193–209. doi:10.1385/BTER:110:3:193.
Adams, J. B., Romdalvik, J., Ramanujam, V. M., & Legator, M. S. (2007). Mercury, lead, and zinc in baby teeth of children with autism versus controls. Journal of Toxicology and Environmental Health A, 70(12), 1046–1051. doi:10.1080/15287390601172080.
American Psychiatric Association. (2000). Diagnostic and statistical manual of mental disorders, fourth edition text revision (DSM-IV-TR). Washington: American Psychiatric Publishing, Inc.
Aschner, M., & Aschner, J. L. (1990). Mercury neurotoxicity: mechanisms of blood-brain barrier transport. Neuroscience and Biobehavioral Reviews, 14(2), 169–176.
ATSDR. (2007). Toxicological profile for arsenic. Retrieved from Agency for Toxic Substances and Disease Registry (ATSDR) http://www.atsdr.cdc.gov/ToxProfiles/tp2.pdf
Becerra, T. A., Wilhelm, M., Olsen, J., Cockburn, M., & Ritz, B. (2013). Ambient air pollution and autism in Los Angeles county, California. Environmental health perspectives, 121(3), 380–386. doi:10.1289/ehp.1205827.
Bellinger, D. C. (2008). Lead neurotoxicity and socioeconomic status: conceptual and analytical issues. Neurotoxicology, 29(5), 828–832. doi:10.1016/j.neuro.2008.04.005.
Bhasin, T. K., & Schendel, D. (2007). Sociodemographic risk factors for autism in a US metropolitan area. Journal of Autism and Developmental Disorders, 37(4), 667–677. doi:10.1007/s10803-006-0194-y.
Blake, J., Hoyme, H. E., & Crotwell, P. L. (2013). A brief history of autism, the autism/vaccine hypothesis and a review of the genetic basis of autism spectrum disorders. South Dakota Journal of Medicine, Spec no, 58-65.
Blanchard, K. S., Palmer, R. F., & Stein, Z. (2011). The value of ecologic studies: mercury concentration in ambient air and the risk of autism. Reviews on Environmental Health, 26(2), 111–118.
Blaurock-Busch, E., Amin, O. R., Dessoki, H. H., & Rabah, T. (2012). Toxic metals and essential elements in hair and severity of symptoms among children with autism. Maedica (Buchar.), 7(1), 38–48.
Block, M. L., & Calderon-Garciduenas, L. (2009). Air pollution: mechanisms of neuroinflammation and CNS disease. Trends in Neurosciences, 32(9), 506–516. doi:10.1016/j.tins.2009.05.009.
Blumberg, S. J., Bramlett, M. D., Kogan, M. D., Schieve, L. A., Jones, J. R., & Lu, M. C. (2013). Changes in prevalence of parent-reported autism spectrum disorder in school-aged U.S. children: 2007 to 2011-2012 (65). Centers for Disease Control and Prevention (CDC). Retrieved from: http://www.cdc.gov/nchs/data/nhsr/nhsr065.pdf
Bryk, A. S., & Raudenbush, S. W. (1992). Hierarchichal linear models: applications and data analysis methods. Newbury Park: Sage Publication.
Butler, B., Likens, G., Cohen, M., & Vermeylen, F. (2007). Mercury in the environment and patterns of mercury deposition from the NADP/MDN mercury deposition network National Oceanic and Atmospheric Administration. Retrieved from: http://www.arl.noaa.gov/documents/reports/MDN_report.pdf
Calderon-Garciduenas, L., Macias-Parra, M., Hoffmann, H. J., Valencia-Salazar, G., Henriquez-Roldan, C., Osnaya, N., et al. (2009). Immunotoxicity and environment: immunodysregulation and systemic inflammation in children. Toxicologic Pathology, 37(2), 161–169. doi:10.1177/0192623308329340.
California Department of Developmental Services. (2003). Autistic spectrum disorders—changes in the California caseload, an update: 1999 Through 2002 California Health and Human Services Agency. Retrieved from: http://www.dds.ca.gov/Autism/docs/AutismReport2003.pdf
Canfield, R. L., Henderson, C. R., Jr., Cory-Slechta, D. A., Cox, C., Jusko, T. A., & Lanphear, B. P. (2003). Intellectual impairment in children with blood lead concentrations below 10 microg per deciliter. New England Journal of Medicine, 348(16), 1517–1526. doi:10.1056/NEJMoa022848.
Croen, L. A., Grether, J. K., Hoogstrate, J., & Selvin, S. (2002). The changing prevalence of autism in California. Journal of Autism and Developmental Disorders, 32(3), 207–215.
DeSoto, M. C., & Hitlan, R. T. (2007). Blood levels of mercury are related to diagnosis of autism: a reanalysis of an important data set. Journal of Child Neurology, 22(11), 1308–1311.
DeSoto, M. C. (2009). Ockham’s Razor and autism: the case for developmental neurotoxins contributing to a disease of neurodevelopment. NeuroToxicology, 30, 331–337.
Diez Roux, A. V. (2004). The study of group-level factors in epidemiology: rethinking variables, study designs, and analytical approaches. Epidemiologic Reviews, 26, 104–111. doi:10.1093/epirev/mxh006.
Durkin, M. S., Maenner, M. J., Meaney, F. J., Levy, S. E., DiGuiseppi, C., Nicholas, J. S., et al. (2010). Socioeconomic inequality in the prevalence of autism spectrum disorder: evidence from a U.S. cross-sectional study. PLoS One, 5(7), e11551. doi:10.1371/journal.pone.0011551.
Enstrom, A., Krakowiak, P., Onore, C., Pessah, I. N., Hertz-Picciotto, I., Hansen, R. L., et al. (2009). Increased IgG4 levels in children with autism disorder. Brain, Behavior, and Immunity, 23(3), 389–395. doi:10.1016/j.bbi.2008.12.005.
Environmental Protection Agency. (2015). National trends in lead levels. Retrieved from Environmental Protection Agency http://www3.epa.gov/airquality/airtrends/lead.html
Evans, G. W., & Kantrowitz, E. (2002). Socioeconomic status and health: the potential role of environmental risk exposure. Annual Review of Public Health, 23, 303–331. doi:10.1146/annurev.publhealth.23.112001.112349.
Fido, A., & Al-Saad, S. (2005). Toxic trace elements in the hair of children with autism. Autism, 9(3), 290–298.
Ha, M., Kwon, H. J., Lim, M. H., Jee, Y. K., Hong, Y. C., Leem, J. H., et al. (2009). Low blood levels of lead and mercury and symptoms of attention deficit hyperactivity in children: a report of the children’s health and environment research (CHEER). Neurotoxicology, 30(1), 31–36. doi:10.1016/j.neuro.2008.11.011.
Herbert, M. R., Russo, J. P., Yang, S., Roohi, J., Blaxill, M., Kahler, S. G., et al. (2006). Autism and environmental genomics. Neurotoxicology, 27(5), 671–684. doi:10.1016/j.neuro.2006.03.017.
Hertz-Picciotto, I., Green, P. G., Delwiche, L., Hansen, R., Walker, C., & Pessah, I. N. (2010). Blood mercury concentrations in CHARGE Study children with and without autism. Environmental Health Perspectives, 118(1), 161–166. doi:10.1289/ehp.0900736.
Holmes, A. S., Blaxill, M. F., & Haley, B. E. (2003). Reduced levels of mercury in first baby haircuts of autistic children. International Journal of Toxicology, 22(4), 277–285.
Jarup, L. (2003). Hazards of heavy metal contamination. British Medical Bulletin, 68, 167–182.
Kalkbrenner, A. E., Daniels, J. L., Chen, J. C., Poole, C., Emch, M., & Morrissey, J. (2010). Perinatal exposure to hazardous air pollutants and autism spectrum disorders at age 8. Epidemiology, 21(5), 631–641. doi:10.1097/EDE.0b013e3181e65d76.
Kern, J. K., Grannemann, B. D., Trivedi, M. H., & Adams, J. B. (2007). Sulfhydryl-reactive metals in autism. Journal of Toxicology and Environmental Health, Part A, 70(8), 715–721.
LaSalle, J. M. (2013). Epigenomic strategies at the interface of genetic and environmental risk factors for autism. Journal of Human Genetics, 58(7), 396–401. doi:10.1038/jhg.2013.49.
Li, X., Chauhan, A., Sheikh, A. M., Patil, S., Chauhan, V., Li, X. M., et al. (2009). Elevated immune response in the brain of autistic patients. Journal of Neuroimmunology, 207(1-2), 111–116. doi:10.1016/j.jneuroim.2008.12.002.
Mazumdar, S., Winter, A., Liu, K. Y., & Bearman, P. (2013). Spatial clusters of autism births and diagnoses point to contextual drivers of increased prevalence. Social Science & Medicine, 95, 87–96. doi:10.1016/j.socscimed.2012.11.032.
Ming, X., Brimacombe, M., Malek, J. H., Jani, N., & Wagner, G. C. (2008). Autism spectrum disorders and identified toxic land fills: co-occurrence across States. Environmental Health Insights, 2, 55–59.
Obrenovich, M. E., Shamberger, R. J., & Lonsdale, D. (2011). Altered heavy metals and transketolase found in autistic spectrum disorder. Biological Trace Element Research, 144(475), 486. doi:10.1007/s12011-011-9146-2.
Ozkaynak, H., Palma, T., Touma, J. S., & Thurman, J. (2008). Modeling population exposures to outdoor sources of hazardous air pollutants. Journal of Exposure Science & Environmental Epidemiology, 18(1), 45–58. doi:10.1038/sj.jes.7500612.
Palmer, R. F., Blanchard, S., Stein, Z., Mandell, D., & Miller, C. (2006). Environmental mercury release, special education rates, and autism disorder: an ecological study of Texas. Health & Place, 12(2), 203–209. doi:10.1016/j.healthplace.2004.11.005.
Palmer, R. F., Blanchard, S., & Wood, R. (2009). Proximity to point sources of environmental mercury release as a predictor of autism prevalence. Health & Place, 15(1), 18–24. doi:10.1016/j.healthplace.2008.02.001.
Payne-Sturges, D. C., Burke, T. A., Breysse, P., Diener-West, M., & Buckley, T. J. (2004). Personal exposure meets risk assessment: a comparison of measured and modeled exposures and risks in an urban community. Environmental Health Perspectives, 112(5), 589–598.
Pinborough-Zimmerman, J., Bilder, D., Bakian, A., Satterfield, R., Carbone, P. S., Nangle, B. E., et al. (2011). Sociodemographic risk factors associated with autism spectrum disorders and intellectual disability. Autism Research, 4(6), 438–448. doi:10.1002/aur.224.
Rahbar, M. H., Samms-Vaughan, M., Ardjomand-Hessabi, M., Loveland, K. A., Dickerson, A. S., Chen, Z., et al. (2012). The role of drinking water sources, consumption of vegetables and seafood in relation to blood arsenic concentrations of Jamaican children with and without Autism Spectrum Disorders. Science of the Total Environment, 433, 362–370. doi:10.1016/j.scitotenv.2012.06.085.
Rahbar, M. H., Samms-Vaughan, M., Loveland, K. A., Ardjomand-Hessabi, M., Chen, Z., Bressler, J., et al. (2013). Seafood consumption and blood mercury concentrations in Jamaican children with and without autism spectrum disorders. Neurotoxicity Research, 23(1), 22–38. doi:10.1007/s12640-012-9321-z.
Rai, D., Lewis, G., Lundberg, M., Araya, R., Svensson, A., Dalman, C., et al. (2012). Parental socioeconomic status and risk of offspring autism spectrum disorders in a Swedish population-based study. Journal of the American Academy of Child and Adolescent Psychiatry, 51(5), 467–476. doi:10.1016/j.jaac.2012.02.012.
Rasmussen, P. E., Levesque, C., Chenier, M., Gardner, H. D., Jones-Otazo, H., & Petrovic, S. (2013). Canadian House Dust Study: population-based concentrations, loads and loading rates of arsenic, cadmium, chromium, copper, nickel, lead, and zinc inside urban homes. Science of the Total Environment, 443, 520–529. doi:10.1016/j.scitotenv.2012.11.003.
Rice, C. E., Baio, J., Van Naarden, B. K., Doernberg, N., Meaney, F. J., & Kirby, R. S. (2007). A public health collaboration for the surveillance of autism spectrum disorders. Paediatric and Perinatal Epidemiology, 21(2), 179–190. doi:10.1111/j.1365-3016.2007.00801.x.
Roberts, A. L., Lyall, K., Hart, J. E., Laden, F., Just, A. C., Bobb, J. F., et al. (2013). Perinatal air pollutant exposures and autism spectrum disorder in the children of nurses’ health study II participants. Environmental Health Perspectives, 121(8), 978–984. doi:10.1289/ehp.1206187.
Roberts, E. M., English, P. B., Grether, J. K., Windham, G. C., Somberg, L., & Wolff, C. (2007). Maternal residence near agricultural pesticide applications and autism spectrum disorders among children in the California Central Valley. Environmental Health Perspectives, 115(10), 1482–1489. doi:10.1289/ehp.10168.
Sanders, T., Liu, Y., Buchner, V., & Tchounwou, P. B. (2009). Neurotoxic effects and biomarkers of lead exposure: a review. Reviews on Environmental Health, 24(1), 15–45
SAS Institute, Inc. (2011) SAS ® Version 9.3. Cary, NC, US. SAS Institute Inc.
Shelton, J. F., Hertz-Picciotto, I., & Pessah, I. N. (2012). Tipping the balance of autism risk: potential mechanisms linking pesticides and autism. Environmental Health Perspectives, 120(7), 944–951. doi:10.1289/ehp.1104553.
Szklo, M., & Nieto, J. (2007). Epidemiology: beyond the basics (2nd ed.). Mississauga: Jones and Barlett.
Thomas, P., Zahorodny, W., Peng, B., Kim, S., Jani, N., Halperin, W., et al. (2012). The association of autism diagnosis with socioeconomic status. Autism, 16(2), 201–213.
Tian, Y., Green, P. G., Stamova, B., Hertz-Picciotto, I., Pessah, I. N., Hansen, R., et al. (2011). Correlations of gene expression with blood lead levels in children with autism compared to typically developing controls. Neurotoxicity Research, 19(1), 1–13. doi:10.1007/s12640-009-9126-x.
USEPA. (2002). Implementation guidance for the arsenic rule—drinking water regulations for arsenic and clarifications to compliance and new source contaminants monitoring. Retrieved from U.S. Environmental Protection Agency http://water.epa.gov/drink/info/arsenic/upload/2005_11_10_arsenic_ars_final_-mainguide_9-13.pdf
USEPA. (2010). The ASPEN Model. Retrieved from http://www.epa.gov/ttn/atw/nata/aspen.html
Van Meter, K. C., Christiansen, L. E., Delwiche, L. D., Azari, R., Carpenter, T. E., & Hertz-Picciotto, I. (2010). Geographic distribution of autism in California: a retrospective birth cohort analysis. Autism Research, 3(1), 19–29. doi:10.1002/aur.110.
Van Naarden, B. K., Pettygrove, S., Daniels, J., Miller, L., Nicholas, J., Baio, J., et al. (2007). Evaluation of a methodology for a collaborative multiple source surveillance network for autism spectrum disorders—Autism and Developmental Disabilities Monitoring Network, 14 sites, United States, 2002. MMWR Surveillance Summaries, 56(1), 29–40.
Volk, H. E., Hertz-Picciotto, I., Delwiche, L., Lurmann, F., & McConnell, R. (2011). Residential proximity to freeways and autism in the CHARGE study. Environmental Health Perspectives, 119(6), 873–877. doi:10.1289/ehp.1002835.
Volk, H. E., Kerin, T., Lurmann, F., Hertz-Picciotto, I., McConnell, R., & Campbell, D. B. (2014). Autism spectrum disorder: interaction of air pollution with the MET receptor tyrosine kinase gene. Epidemiology, 25(1), 44–47. doi:10.1097/EDE.0000000000000030.
Windham, G. C., Zhang, L., Gunier, R., Croen, L. A., & Grether, J. K. (2006). Autism spectrum disorders in relation to distribution of hazardous air pollutants in the San Francisco Bay area. Environmental Health Perspectives, 114(9), 1438–1444.
Zablotsky, B., Black, L. A., Maenner, M. J., Schieve, L., & Blumberg, S. J. (2015). Estimated Prevalence of Autism ad Other Developmental Disabilities Following Questionnaire Changes in the 2014 National Health Interview Survey (87). Centers for Disease Control and Prevention. Retrieved from: http://www.cdc.gov/nchs/data/nhsr/nhsr087.pdf
Zheng, W., Aschner, M., & Ghersi-Egea, J. F. (2003). Brain barrier systems: a new frontier in metal neurotoxicological research. Toxicology and Applied Pharmacology, 192(1), 1–11.
Acknowledgments
We acknowledge the assistance of the National Center of Birth Defects and Developmental Disabilities of the CDC, especially the guidance provided by Jon Baio and Lin Hui Tian. We also acknowledge the support and resources provided by the Biostatistics/Epidemiology/Research Design (BERD) component of the Center for Clinical and Translational Sciences (CCTS) for this project. CCTS is mainly funded by the NIH Centers for Translational Science Award (NIH CTSA) grant (UL1 RR024148), and its renewal (UL1 TR000371) awarded to the University of Texas Health Science Center at Houston by the National Center for Research Resources (NCRR) and the National Center for Advancing Translational Sciences (NCATS), awarded to University of Texas Health Science Center at Houston. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NCRR, NCATS, or the CDC.
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Dickerson, A.S., Rahbar, M.H., Bakian, A.V. et al. Autism spectrum disorder prevalence and associations with air concentrations of lead, mercury, and arsenic. Environ Monit Assess 188, 407 (2016). https://doi.org/10.1007/s10661-016-5405-1
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DOI: https://doi.org/10.1007/s10661-016-5405-1