Prenatal air pollution, maternal immune activation, and autism spectrum disorder

Xin Yu; Md Mostafijur Rahman; Sarah A Carter; Jane C Lin; Zimin Zhuang; Ting Chow; Frederick W Lurmann; Michael J Kleeman; Mayra P Martinez; Aaron van Donkelaar; Randall V Martin; Sandrah P Eckel; Zhanghua Chen; Pat Levitt; Joel Schwartz; Daniel Hackman; Jiu-Chiuan Chen; Rob McConnell; Anny H Xiang

doi:10.1016/j.envint.2023.108148

Prenatal air pollution, maternal immune activation, and autism spectrum disorder

Environ Int. 2023 Sep:179:108148. doi: 10.1016/j.envint.2023.108148. Epub 2023 Aug 14.

Authors

Xin Yu¹, Md Mostafijur Rahman², Sarah A Carter³, Jane C Lin³, Zimin Zhuang³, Ting Chow³, Frederick W Lurmann⁴, Michael J Kleeman⁵, Mayra P Martinez³, Aaron van Donkelaar⁶, Randall V Martin⁶, Sandrah P Eckel⁷, Zhanghua Chen⁷, Pat Levitt⁸, Joel Schwartz⁹, Daniel Hackman¹⁰, Jiu-Chiuan Chen⁷, Rob McConnell⁷, Anny H Xiang¹¹

Affiliations

¹ Spatial Science Institute, University of Southern California, Los Angeles, CA, USA.
² Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Department of Environmental Health Sciences, Tulane University School of Public Health and Tropical Medicine, USA.
³ Department of Research & Evaluation, Kaiser Permanente Southern California, Pasadena, CA, USA.
⁴ Sonoma Technology, Inc., Petaluma, CA, USA.
⁵ Department of Civil and Environmental Engineering, University of California, Davis, Davis, CA,USA.
⁶ Department of Energy, Environmental & Chemical Engineering, Washington University at St. Louis, St. Louis, MO 63130, USA.
⁷ Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁸ Department of Pediatrics and Program in Developmental Neuroscience and Neurogenetics, Keck School of Medicine, The Saban Research Institute, Children's Hospital Los Angeles, University of Southern California, Los Angeles, CA, USA.
⁹ Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
¹⁰ USC Suzanne Dworak-Peck School of Social Work, University of Southern California, Los Angeles, CA, USA.
¹¹ Department of Research & Evaluation, Kaiser Permanente Southern California, Pasadena, CA, USA. Electronic address: anny.h.xiang@kp.org.

Abstract

Background: Autism Spectrum Disorder (ASD) risk is highly heritable, with potential additional non-genetic factors, such as prenatal exposure to ambient particulate matter with aerodynamic diameter < 2.5 µm (PM_2.5) and maternal immune activation (MIA) conditions. Because these exposures may share common biological effect pathways, we hypothesized that synergistic associations of prenatal air pollution and MIA-related conditions would increase ASD risk in children.

Objectives: This study examined interactions between MIA-related conditions and prenatal PM_2.5 or major PM_2.5 components on ASD risk.

Methods: In a population-based pregnancy cohort of children born between 2001 and 2014 in Southern California, 318,751 mother-child pairs were followed through electronic medical records (EMR); 4,559 children were diagnosed with ASD before age 5. Four broad categories of MIA-related conditions were classified, including infection, hypertension, maternal asthma, and autoimmune conditions. Average exposures to PM_2.5 and four PM_2.5 components, black carbon (BC), organic matter (OM), nitrate (NO₃^-), and sulfate (SO₄^2-), were estimated at maternal residential addresses during pregnancy. We estimated the ASD risk associated with MIA-related conditions, air pollution, and their interactions, using Cox regression models to adjust for covariates.

Results: ASD risk was associated with MIA-related conditions [infection (hazard ratio 1.11; 95% confidence interval 1.05-1.18), hypertension (1.30; 1.19-1.42), maternal asthma (1.22; 1.08-1.38), autoimmune disease (1.19; 1.09-1.30)], with higher pregnancy PM_2.5 [1.07; 1.03-1.12 per interquartile (3.73 μg/m³) increase] and with all four PM_2.5 components. However, there were no interactions of each category of MIA-related conditions with PM_2.5 or its components on either multiplicative or additive scales.

Conclusions: MIA-related conditions and pregnancy PM_2.5 were independently associations with ASD risk. There were no statistically significant interactions of MIA conditions and prenatal PM_2.5 exposure with ASD risk.

Keywords: Autism spectrum disorders; Interaction; PM(2.5); PM(2.5) chemical components; Susceptibility.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Air Pollution* / adverse effects
Asthma*
Autism Spectrum Disorder* / epidemiology
Autism Spectrum Disorder* / etiology
Child, Preschool
Female
Humans
Hypertension*
Pregnancy
Vitamins

Substances

Vitamins

Abstract

Publication types

MeSH terms

Substances

Grants and funding