A Systematic Review of Air Pollution Exposure and Brain Structure and Function during Development

Abstract

Objectives: Air pollutants are known neurotoxicants. In this updated systematic review, we evaluate new evidence since our 2019 systematic review on the effect of outdoor air pollution exposure on childhood and adolescent brain structure and function as measured by magnetic resonance imaging (MRI).

Methods: Using PubMed and Web of Science, we conducted an updated literature search and systematic review of articles published through March 2024, using key terms for air pollution and functional and/or structural MRI. Two raters independently screened all articles using Covidence and implemented the risk of bias instrument for systematic reviews informing the World Health Organization Global Air Quality Guidelines.

Results: We identified 222 relevant papers, and 14 new studies met our inclusion criteria. Including six studies from our 2019 review, the 20 publications to date include study populations from the United States, Netherlands, Spain, and United Kingdom. Studies investigated exposure periods spanning pregnancy through early adolescence, and estimated air pollutant exposure levels via personal monitoring, geospatial residential estimates, or school courtyard monitors. Brain MRI occurred when children were on average 6-14.7 years old; however, one study assessed newborns. Several MRI modalities were leveraged, including structural morphology, diffusion tensor imaging, restriction spectrum imaging, arterial spin labeling, magnetic resonance spectroscopy, as well as resting-state and task-based functional MRI. Air pollutants were associated with widespread brain differences, although the magnitude and direction of findings are largely inconsistent, making it difficult to draw strong conclusions.

Conclusion: Prenatal and childhood exposure to outdoor air pollution is associated with structural and functional brain variations. Compared to our initial 2019 review, publications doubled-an increase that testifies to the importance of this public health issue. Further research is needed to clarify the effects of developmental timing, along with the downstream implications of outdoor air pollution exposure on children's cognitive and mental health.

Keywords: air pollution; magnetic resonance imaging; neurodevelopment; neurotoxicity; particulate matter.

Figure 1.. PRISMA flow diagram of study selection for review focused on air pollution and brain MRI in children and adolescents.

Figure 2.. A) Map of study locations for air pollution and brain MRI findings in children and adolescents (n=20 studies). Cohort and study sample details can be found in Table 2. B) Map of PM_2.5 exposure levels worldwide based on IQAir World Health Organization 2023 data.

Most included studies have come from countries that currently have relatively low levels of exposure to air pollution; albeit exposure levels for any given study may be higher given some studies examined exposure during pregnancy as far back as 1998 when air pollution levels were markedly higher in Western countries. Abbreviations: ABCD = Adolescent Brain Cognitive Development Study; BREATHE = Brain Development and Air Pollution Ultrafine Particles in School Children Project; CCAAPS = Cincinnati Childhood Allergy and Air Pollution Study; CCCEH = Columbia Center for Children’s Environmental Health Cohort; dHCP = Developing Human Connectome Project; ELS = Early Life Stress on Neurodevelopment Study; Generation R = Generation R Study; WHO = World Health Organization. Created with Biorender.

Figure 3.. A) Summary of air pollution exposures across studies, including exposure estimation methodology, primary exposure(s), and timing of interest; B) Summary of MRI outcomes for brain structure and function across studies, including MRI modality methodology and study design for MRI outcomes.

Abbreviations: NO₂ = Nitrogen Dioxide; PAH = Polycyclic Aromatic Hydrocarbon; PM_2.5 = Fine Particulate Matter; PM₁₀ = Coarse Particulate Matter. ASL = Arterial Spin Labeling; DTI = Diffusion Tensor Imaging; MRI = Magnetic Resonance Imaging; MRS = Magnetic Resonance Spectroscopy; rs-fMRI= Resting State Functional Magnetic Resonance Imaging; RSI = Restriction Spectrum Imaging; sMRI: Structural Magnetic Resonance Imaging. Created with Biorender.

Figure 4.. A) Structural Magnetic Resonance Imaging (MRI) brain regions commonly identified across multiple studies. B) Illustration of variable timing of exposure and volumetric outcomes across select studies including in review.

Summary of MRI outcomes for brain structure and function across studies, including MRI modality methodology and study design for MRI outcomes. Abbreviations: IFG = inferior frontal gyrus; SA = Surface Area. PM = particulate matter; NO₂ = nitrogen dioxide. ABCD = Adolescent Brain Cognitive Development Study; BREATHE = Brain Development and Air Pollution Ultrafine Particles in School Children Project; CCAAPS = Cincinnati Childhood Allergy and Air Pollution Study; CCCEH = Columbia Center for Children’s Environmental Health Cohort; dHCP = Developing Human Connectome Project; ELS = Early Life Stress on Neurodevelopment Study; Generation R = Generation R Study. Created with Biorender.

Figure 5.. A) Diffusion-weighted MRI brain regions commonly identified across multiple studies. B) Illustration of variable timing of exposure and diffusion-weighted imaging outcomes across all five included studies.

Summary of MRI outcomes for brain structure and function across studies, including MRI modality methodology and study design for MRI outcomes. Abbreviations: AD = axial diffusivity; FA = fractional anisotropy; IFO = inferior longitudinal occipital; ILF = inferior longitudinal fasciculus; MD = mean diffusivity; RSI = restricted spectrum imaging; SLF = superior longitudinal fasciculus. PM = particulate matter; NO₂ = nitrogen dioxide. ABCD = Adolescent Brain Cognitive Development Study; BREATHE = Brain Development and Air Pollution Ultrafine Particles in School Children Project; CCCEH = Columbia Center for Children’s Environmental Health Cohort; Generation R = Generation R Study. Created with Biorender.

Figure 6.. Risk of bias summary.

Risk of bias was determined using the WHO Global Air Quality Guidelines. In the figure above, tan indicates low risk of bias, orange indicates some concerns regarding potential bias, and red indicates high risk of bias. Most studies included in this review were found to have low to moderate risk of bias, mostly due to missing data, while a select few demonstrate high risk of bias due to confounding factors.