title: A Systematic Review and Meta-Analysis of Multiple Airborne Pollutants and Autism Spectrum Disorder.
abstract: BACKGROUND
  Exposure to ambient air pollution is widespread and may be detrimental to human brain development and a potential risk factor for Autism Spectrum Disorder (ASD). We conducted a systematic review of the human evidence on the relationship between ASD and exposure to all airborne pollutants, including particulate matter air pollutants and others (e.g. pesticides and metals).
  
  
  OBJECTIVE
  To answer the question: "is developmental exposure to air pollution associated with ASD?"
  
  
  METHODS
  We conducted a comprehensive search of the literature, identified relevant studies using inclusion/exclusion criteria pre-specified in our protocol (registered in PROSPERO, CRD # 42015017890), evaluated the potential risk of bias for each included study and identified an appropriate subset of studies to combine in a meta-analysis. We then rated the overall quality and strength of the evidence collectively across all air pollutants.
  
  
  RESULTS
  Of 1,158 total references identified, 23 human studies met our inclusion criteria (17 case-control, 4 ecological, 2 cohort). Risk of bias was generally low across studies for most domains; study limitations were related to potential confounding and accuracy of exposure assessment methods. We rated the quality of the body of evidence across all air pollutants as "moderate." From our meta-analysis, we found statistically significant summary odds ratios (ORs) of 1.07 (95% CI: 1.06, 1.08) per 10-μg/m3 increase in PM10 exposure (n = 6 studies) and 2.32 (95% CI: 2.15, 2.51) per 10-μg/m3 increase in PM2.5 exposure (n = 3 studies). For pollutants not included in a meta-analysis, we collectively evaluated evidence from each study in rating the strength and quality of overall evidence considering factors such as inconsistency, imprecision, and evidence of dose-response. All included studies generally showed increased risk of ASD with increasing exposure to air pollution, although not consistently across all chemical components.
  
  
  CONCLUSIONS
  After considering strengths and limitations of the body of research, we concluded that there is "limited evidence of toxicity" for the association between early life exposure to air pollution as a whole and diagnosis of ASD. The strongest evidence was between prenatal exposure to particulate matter and ASD. However, the small number of studies in the meta-analysis and unexplained statistical heterogeneity across the individual study estimates means that the effect could be larger or smaller (including not significant) than these studies estimate. Our research supports the need for health protective public policy to reduce exposures to harmful airborne contaminants among pregnant women and children and suggests opportunities for optimizing future research.
authors.affiliation: Department of Obstetrics, Gynecology & Reproductive Sciences, Program on Reproductive Health and the Environment, University of California, San Francisco, CA, United States of America.
authors.forename: Juleen
authors.initials: J
authors.lastname: Lam
authors.affiliation: Department of Obstetrics, Gynecology & Reproductive Sciences, Program on Reproductive Health and the Environment, University of California, San Francisco, CA, United States of America.
authors.forename: Patrice
authors.initials: P
authors.lastname: Sutton
authors.affiliation: Joseph J. Zilber School of Public Health, University of Wisconsin-Milwaukee, Milkwaukee, WI, United States of America.
authors.forename: Amy
authors.initials: A
authors.lastname: Kalkbrenner
authors.affiliation: Division of Environmental and Occupational Disease Control, California Department of Public Health, Richmond, CA, United States of America.
authors.forename: Gayle
authors.initials: G
authors.lastname: Windham
authors.affiliation: Autism Science Foundation, New York, NY, United States of America.|Department of Pharmacology and Toxicology, Rutgers University, New Brunswick, NJ, United States of America.
authors.forename: Alycia
authors.initials: A
authors.lastname: Halladay
authors.affiliation: Scientific consultant to the University of California, San Francisco, CA, United States of America.
authors.forename: Erica
authors.initials: E
authors.lastname: Koustas
authors.affiliation: Division of Extramural Research and Training, National Institute of Environmental Health Sciences, Research Triangle Park, NC, United States of America.
authors.forename: Cindy
authors.initials: C
authors.lastname: Lawler
authors.affiliation: Department of Obstetrics and Gynecology, Kaiser Permanente, Oakland, CA, United States of America.
authors.forename: Lisette
authors.initials: L
authors.lastname: Davidson
authors.affiliation: Department of Obstetrics, Gynecology & Reproductive Sciences, Program on Reproductive Health and the Environment, University of California, San Francisco, CA, United States of America.
authors.forename: Natalyn
authors.initials: N
authors.lastname: Daniels
authors.affiliation: Department of Epidemiology and Biostatistics, Drexel University, Philadelphia, PA, United States of America.
authors.forename: Craig
authors.initials: C
authors.lastname: Newschaffer
authors.affiliation: Department of Obstetrics, Gynecology & Reproductive Sciences, Program on Reproductive Health and the Environment, University of California, San Francisco, CA, United States of America.
authors.forename: Tracey
authors.initials: T
authors.lastname: Woodruff