Autism Spectrum Disorder and Particulate Matter Air Pollution before, during, and after Pregnancy: A Nested Case–Control Analysis within the Nurses’ Health Study II Cohort

Background Autism spectrum disorder (ASD) is a developmental disorder with increasing prevalence worldwide, yet has unclear etiology. Objective We explored the association between maternal exposure to particulate matter (PM) air pollution and odds of ASD in her child. Methods We conducted a nested case–control study of participants in the Nurses’ Health Study II (NHS II), a prospective cohort of 116,430 U.S. female nurses recruited in 1989, followed by biennial mailed questionnaires. Subjects were NHS II participants’ children born 1990–2002 with ASD (n = 245), and children without ASD (n = 1,522) randomly selected using frequency matching for birth years. Diagnosis of ASD was based on maternal report, which was validated against the Autism Diagnostic Interview-Revised in a subset. Monthly averages of PM with diameters ≤ 2.5 μm (PM2.5) and 2.5–10 μm (PM10–2.5) were predicted from a spatiotemporal model for the continental United States and linked to residential addresses. Results PM2.5 exposure during pregnancy was associated with increased odds of ASD, with an adjusted odds ratio (OR) for ASD per interquartile range (IQR) higher PM2.5 (4.42 μg/m3) of 1.57 (95% CI: 1.22, 2.03) among women with the same address before and after pregnancy (160 cases, 986 controls). Associations with PM2.5 exposure 9 months before or after the pregnancy were weaker in independent models and null when all three time periods were included, whereas the association with the 9 months of pregnancy remained (OR = 1.63; 95% CI: 1.08, 2.47). The association between ASD and PM2.5 was stronger for exposure during the third trimester (OR = 1.42 per IQR increase in PM2.5; 95% CI: 1.09, 1.86) than during the first two trimesters (ORs = 1.06 and 1.00) when mutually adjusted. There was little association between PM10–2.5 and ASD. Conclusions Higher maternal exposure to PM2.5 during pregnancy, particularly the third trimester, was associated with greater odds of a child having ASD. Citation Raz R, Roberts AL, Lyall K, Hart JE, Just AC, Laden F, Weisskopf MG. 2015. Autism spectrum disorder and particulate matter air pollution before, during, and after pregnancy: a nested case–control analysis within the Nurses’ Health Study II cohort. Environ Health Perspect 123:264–270; http://dx.doi.org/10.1289/ehp.1408133

[1]  Irva Hertz-Picciotto,et al.  Traffic-related air pollution, particulate matter, and autism. , 2013, JAMA psychiatry.

[2]  N. Minshew,et al.  Evidence for dysregulation of axonal growth and guidance in the etiology of ASD , 2013, Front. Hum. Neurosci..

[3]  G. Chodick,et al.  A Survey of Out-of-Pocket Expenditures for Children with Autism Spectrum Disorder in Israel , 2013, Journal of autism and developmental disorders.

[4]  M. Lipsitch,et al.  Negative Controls: A Tool for Detecting Confounding and Bias in Observational Studies , 2010, Epidemiology.

[5]  Sharon E. Edwards,et al.  Race, socioeconomic status, and air pollution exposure in North Carolina. , 2013, Environmental research.

[6]  Andrés Martin,et al.  Health care expenditures associated with autism spectrum disorders. , 2007, Archives of pediatrics & adolescent medicine.

[7]  Francine Laden,et al.  Perinatal Air Pollutant Exposures and Autism Spectrum Disorder in the Children of Nurses’ Health Study II Participants , 2013, Environmental health perspectives.

[8]  M. Block,et al.  Particulate matter, oxidative stress and neurotoxicity. , 2008, Neurotoxicology.

[9]  Christopher J. Paciorek,et al.  Predicting Chronic Fine and Coarse Particulate Exposures Using Spatiotemporal Models for the Northeastern and Midwestern United States , 2008, Environmental health perspectives.

[10]  A. Nel,et al.  Ultrafine particulate pollutants induce oxidative stress and mitochondrial damage. , 2002, Environmental health perspectives.

[11]  J. Constantino,et al.  Reciprocal Social Behavior in Children With and Without Pervasive Developmental Disorders , 2000, Journal of developmental and behavioral pediatrics : JDBP.

[12]  R. Shumway,et al.  Air Pollution and Lymphocyte Phenotype Proportions in Cord Blood , 2005, Environmental health perspectives.

[13]  D. German,et al.  Neuropathology and Animal Models of Autism: Genetic and Environmental Factors , 2013, Autism research and treatment.

[14]  P. Patterson,et al.  Maternal infection and immune involvement in autism. , 2011, Trends in molecular medicine.

[15]  Beate Ritz,et al.  Ambient Air Pollution and Autism in Los Angeles County, California , 2012, Environmental health perspectives.

[16]  C. Rice,et al.  Medical Expenditures for Children with an Autism Spectrum Disorder in a Privately Insured Population , 2008, Journal of autism and developmental disorders.

[17]  M. Ferreri,et al.  [Pervasive developmental disorders]. , 2014, La Revue du praticien.

[18]  L. Lee,et al.  Maternal Smoking during Pregnancy and the Prevalence of Autism Spectrum Disorders, Using Data from the Autism and Developmental Disabilities Monitoring Network , 2012, Environmental health perspectives.

[19]  Duanping Liao,et al.  Spatio-temporal modeling of particulate air pollution in the conterminous United States using geographic and meteorological predictors , 2014, Environmental Health.

[20]  N. Saunders,et al.  Developmental neurotoxicity of industrial chemicals , 2007, The Lancet.

[21]  I. Quaak,et al.  The Dynamics of Autism Spectrum Disorders: How Neurotoxic Compounds and Neurotransmitters Interact , 2013, International journal of environmental research and public health.

[22]  P. Rodier,et al.  Developing brain as a target of toxicity. , 1995, Environmental health perspectives.

[23]  Julie Daniels,et al.  The epidemiology of autism spectrum disorders. , 2007, Annual review of public health.

[24]  Sarah Wong,et al.  Evidence of reactive oxygen species-mediated damage to mitochondrial DNA in children with typical autism , 2013, Molecular Autism.

[25]  Lara Delmolino,et al.  Pervasive developmental disorders , 2007 .

[26]  Lora D. Delwiche,et al.  Residential Proximity to Freeways and Autism in the CHARGE Study , 2010, Environmental health perspectives.

[27]  A. Depino.  Peripheral and central inflammation in autism spectrum disorders , 2013, Molecular and Cellular Neuroscience.

[28]  Beate Ritz,et al.  Predicting traffic-related air pollution in Los Angeles using a distance decay regression selection strategy. , 2009, Environmental research.

[29]  A. Couteur,et al.  Autism Diagnostic Interview-Revised: A revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders , 1994, Journal of autism and developmental disorders.

[30]  Eric Courchesne,et al.  Patches of disorganization in the neocortex of children with autism. , 2014, The New England journal of medicine.

[31]  Erik T Parner,et al.  Maternal Infection Requiring Hospitalization During Pregnancy and Autism Spectrum Disorders , 2010, Journal of autism and developmental disorders.

[32]  J. Manson,et al.  A prospective study of pregravid determinants of gestational diabetes mellitus. , 1997, JAMA.

[33]  F. Perera,et al.  Prenatal Airborne Polycyclic Aromatic Hydrocarbon Exposure and Child IQ at Age 5 Years , 2009, Pediatrics.

[34]  D. Spiegelman,et al.  Fertility therapies, infertility and autism spectrum disorders in the Nurses' Health Study II. , 2012, Paediatric and perinatal epidemiology.

[35]  E. Fombonne,et al.  Epidemiology of Autism Spectrum Disorders , 2014 .

[36]  I. Hertz-Picciotto,et al.  Prenatal exposures to persistent and non-persistent organic compounds and effects on immune system development. , 2008, Basic & clinical pharmacology & toxicology.

[37]  W. McMahon,et al.  Autistic disorder and viral infections , 2005, Journal of NeuroVirology.

[38]  Rosalind J Wright,et al.  Association of black carbon with cognition among children in a prospective birth cohort study. , 2007, American journal of epidemiology.

[39]  Abraham Silvers,et al.  Influence of Prenatal Mercury Exposure Upon Scholastic and Psychological Test Performance: Benchmark Analysis of a New Zealand Cohort , 1998, Risk analysis : an official publication of the Society for Risk Analysis.

[40]  Donald R Mattison,et al.  Environmental Exposures and Adverse Pregnancy Outcomes: A Review of the Science , 2008, Reproductive Sciences.

[41]  S. Horvath,et al.  Transcriptomic Analysis of Autistic Brain Reveals Convergent Molecular Pathology , 2011, Nature.

[42]  David S. Mandell,et al.  Medicaid Expenditures for Children with Autistic Spectrum Disorders: 1994 to 1999 , 2006, Journal of autism and developmental disorders.

[43]  L. Croen,et al.  Autism Spectrum Disorders in Relation to Distribution of Hazardous Air Pollutants in the San Francisco Bay Area , 2006, Environmental health perspectives.

[44]  Erik T Parner,et al.  Recurrence of autism spectrum disorders in full- and half-siblings and trends over time: a population-based cohort study. , 2013, JAMA pediatrics.

[45]  R. Hansen,et al.  Increased Anti-Phospholipid Antibodies in Autism Spectrum Disorders , 2013, Mediators of inflammation.

[46]  L. Lotspeich,et al.  A Comparison of Health Care Utilization and Costs of Children With and Without Autism Spectrum Disorders in a Large Group-Model Health Plan , 2006, Pediatrics.

[47]  Sydney Abbey,et al.  What is A “Method”? , 1991 .

[48]  J. Constantino,et al.  Validation of a Brief Quantitative Measure of Autistic Traits: Comparison of the Social Responsiveness Scale with the Autism Diagnostic Interview-Revised , 2003, Journal of autism and developmental disorders.

[49]  Mitchel Klein,et al.  A Method for Detection of Residual Confounding in Time-series and Other Observational Studies , 2011, Epidemiology.

[50]  Joel Schwartz,et al.  Spatio-temporal modeling of chronic PM10 exposure for the Nurses' Health Study. , 2008, Atmospheric environment.

[51]  C. Lajonchere,et al.  Genetic heritability and shared environmental factors among twin pairs with autism. , 2011, Archives of general psychiatry.

[52]  D. Rice,et al.  Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. , 2000, Environmental health perspectives.