Association between prenatal air pollutant exposure and autism spectrum disorders in young children: A matched case-control study in Canada

Malia Sq Murphy; Kasim E Abdulaziz; Éric Lavigne; Erica Erwin; Yanfang Guo; Alysha Lj Dingwall-Harvey; David Stieb; Mark C Walker; Shi Wu Wen; Hwashin Hyun Shin

doi:10.1016/j.envres.2024.119706

Association between prenatal air pollutant exposure and autism spectrum disorders in young children: A matched case-control study in Canada

Environ Res. 2024 Nov 15:261:119706. doi: 10.1016/j.envres.2024.119706. Epub 2024 Jul 30.

Authors

Affiliations

¹ Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
² Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Better Outcomes Registry & Network (BORN) Ontario, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada; School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada.
³ School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada; Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, Canada.
⁴ Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Better Outcomes Registry & Network (BORN) Ontario, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
⁵ Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
⁶ Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Better Outcomes Registry & Network (BORN) Ontario, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada; School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada; Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada; Department of Obstetrics and Gynecology, University of Ottawa, Ottawa, Ontario, Canada; Department of Obstetrics, Gynecology & Newborn Care, Ottawa, Canada; International and Global Health Office, University of Ottawa, Ottawa, Canada.
⁷ Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada; Department of Obstetrics and Gynecology, University of Ottawa, Ottawa, Ontario, Canada; Department of Obstetrics, Gynecology & Newborn Care, Ottawa, Canada.
⁸ Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, Canada; Department of Mathematics and Statistics, Queen's University, Kingston, Ontario, Canada. Electronic address: hwashin.shin@hc-sc.gc.ca.

PMID: 39084506
DOI: 10.1016/j.envres.2024.119706

Abstract

The direction and magnitude of association between maternal exposure to ambient air pollutants across gestational windows and offspring risk of autism spectrum disorders (ASD) remains unclear. We sought to evaluate the time-varying effects of prenatal air pollutant exposure on ASD. We conducted a matched case-control study of singleton term children born in Ontario, Canada from 1-Apr-2012 to 31-Dec-2016. Provincial birth registry data were linked with applied behavioural analysis services and ambient air pollutant datasets to ascertain prenatal exposure to nitrogen dioxide (NO₂), ground-level ozone (O₃), fine particulate matter (PM_2.5), and ASD diagnoses. Covariate balance between cases and controls was established using coarsened exact matching. Conditional logistic regression was used to assess the association between prenatal air pollutant exposure and ASD. Distributed lag non-linear models (DLNM) were used to examine the effects of single-pollutant exposure by prenatal week. Sensitivity analyses were conducted to assess the impact of exposure period on the observed findings. The final sample included 1589 ASD cases and 7563 controls. Compared to controls, cases were more likely to be born to mothers living in urban areas, delivered by Caesarean section, and assigned male sex at birth. NO₂ was a consistent and significant contributor to ASD risk after accounting for co-exposure to O₃, PM_2.5 and covariates. The odds ratio per interquartile range increase was 2.1 (95%CI 1.8-2.3) pre-conception, 2.2 (2.0-2.5) for the 1st trimester, 2.2 (1.9-2.5) for the 2nd trimester, and 2.1 (1.9-2.4) for the 3rd trimester. In contrast, findings for O₃ and PM_2.5 with ASD were inconsistent. Findings from DLNM and sensitivity analyses were similar. Exposure to NO₂ before and during pregnancy was significantly associated with ASD in offspring. The relationship between prenatal O₃ and PM_2.5 exposure and ASD remains unclear. Further investigation into the combined effects of multi-pollutant exposure on child neurodevelopment is warranted.

Keywords: Air pollution; Autism spectrum disorder; Matched case-control; Odds ratio; Prenatal exposure; Time-varying effects.

MeSH terms

Adult
Air Pollutants* / analysis
Air Pollutants* / toxicity
Air Pollution / adverse effects
Air Pollution / analysis
Autism Spectrum Disorder* / chemically induced
Autism Spectrum Disorder* / epidemiology
Case-Control Studies
Child
Child, Preschool
Female
Humans
Infant
Male
Maternal Exposure* / adverse effects
Nitrogen Dioxide* / analysis
Ontario / epidemiology
Ozone / analysis
Particulate Matter* / analysis
Pregnancy
Prenatal Exposure Delayed Effects* / chemically induced
Prenatal Exposure Delayed Effects* / epidemiology

Substances

Air Pollutants
Nitrogen Dioxide
Particulate Matter
Ozone