Air pollution exposure during early life can have lasting effects on the brain’s white matter

Exposure to certain pollutants, like fine particles (PM_2.5) and nitrogen oxides (NO_x), during pregnancy and childhood is associated with differences in the microstructure of the brain´s white matter, and some of these effects persist throughout adolescence. These are the main conclusions of a study led by the Barcelona Institute for Global Health (ISGlobal), a centre supported by “la Caixa” Foundation. The findings, published in Environmental Research, highlight the importance of addressing air pollution as a public health issue, particularly for pregnant women and children. 

An increasing amount of evidence suggests that air pollution affects neurodevelopment in children. Recent studies using imaging techniques have looked at the impact of air pollutants on the brain’s white matter, which plays a crucial role in connecting different brain regions. However, these studies were limited in that they only looked at one timepoint and did not follow the participants throughout childhood.

“Following participants throughout childhood and including two neuroimaging assessments for each child would shed new light on whether the effects of air pollution on white matter persist, attenuate, or worsen,” says ISGlobal researcher Mònica Guxens. And that is what she and her team did.

The study involved over 4,000 participants who had been followed since birth as part of the Generation R Study in Rotterdam, the Netherlands. The research team estimated the amount of exposure to 14 different air pollutants during pregnancy and childhood, based on where the families lived. For 1,314 children, the researchers were able to use data from two brain scans - one performed around 10 years of age and another around 14 years of age - to examine changes in white matter microstructure. 

Some effects persist, some diminish over time

The analysis found that exposure to certain pollutants, like fine particles (PM_2.5) and nitrogen oxides (NO_x), was linked to differences in the development of white matter in the brain. Specifically, higher exposure to PM_2.5 during pregnancy, and higher exposure to PM_2.5, PM₁₀, PM_2.5-10, and NO_x during childhood were associated with lower levels of a measure called fractional anisotropy, which measures how water molecules diffuse within the brain. In more mature brains, water flows more in one direction than in all directions, which gives higher values for this marker. This association persisted throughout adolescence (i.e. it was also observed in the second scan), suggesting a long-term impact of air pollution on brain development. Every increase in exposure level to air pollution corresponded to more than a 5-month delay in the development of fractional anisotropy.

“We think that the lower fractional anisotropy is likely the result of changes in myelin, the protective sheath that forms around the nerves, rather than in the structure or packaging of the nerve fibers” says Michelle Kusters, ISGlobal researcher and first author of the study. How air pollutants affect myelin is not fully understood, but could be linked to the entrance of small particles directly to the brain or to inflammatory mediators produced by the body when the particles enter the lungs. Together, this would lead to neuroinflammation, oxidative stress, and eventually neuronal death, as documented in animal studies.

The study also found that some pollutants were linked to changes in another measure of white matter, called mean diffusivity, which reflects the integrity of white matter, and which tends to decrease as the brain matures. Higher exposure to pollutants like silicon in fine particles (PM_2.5) during pregnancy was associated with initially higher mean diffusivity, which then decreased more rapidly as the children grew older. This indicates that some effects of air pollution may diminish over time.

Policy implications

Overall, the study suggests that air pollution exposure, both during pregnancy and early childhood, can have lasting effects on the brain’s white matter. “Even if the size of the effects were small, this can have a meaningful impact on a population scale,” says Guxens.

Importantly, these findings were present in children exposed to PM_2.5 and PM₁₀ concentrations above the currently recommended maximum values by the WHO but below those currently recommended by the European Union. “Our study provides support to the need for more stringent European guidelines on air pollution, which are expected to be approved soon by the European Parliament,” adds Guxens.

In a previous study, Guxens and her team showed that white matter microstructure can also be affected by early exposure to heat and cold, especially in children living in poorer neighbourhoods.

Reference

Kusters MW, Lopez-Vicente M, Muetzel RL et al. Residential ambient air pollution exposure and the development of white matter microstructure throughout adolescence. Environ Res. 2024. doi: 10.1016/j.envres.2024.119828.2024.

About ISGlobal

The Barcelona Institute for Global Health, ISGlobal, is the fruit of an innovative alliance between the ”la Caixa” Foundation and academic and government institutions to contribute to the efforts undertaken by the international community to address the challenges in global health. ISGlobal is a consolidated hub of excellence in research that has grown out of work first started in the world of health care by the Hospital Clínic and the Parc de Salut MAR and in the academic sphere by the University of Barcelona and Pompeu Fabra University. Its working model is based on the generation of scientific knowledge through Research Programmes and Groups, and its translation through the areas of Training and Analysis and Global Development. ISGlobal has been named a Severo Ochoa Centre of Excellence and is a member of the CERCA system of the Generalitat de Catalunya.