Exposure to heat and cold in early life may affect development of white matter in the brain

In the current climate emergency, the impact of extreme temperatures on human health is a major concern for the scientific community and society. Children are particularly vulnerable to temperature changes, as their thermoregulation mechanisms are still immature.

"We know that the developing brain of foetuses and children is particularly susceptible to environmental exposures, and there is some preliminary evidence suggesting that exposure to cold and heat may affect mental well-being and cognitive performance in children and adolescents," says Mònica Guxens, researcher at ISGlobal, Erasmus MC and CIBERESP. "However, there is a lack of studies evaluating potential changes in brain structure as a result of these exposures," she adds.

In this study, a team led by Guxens looked at the white matter structure in the brains of preadolescents to identify windows of susceptibility to cold and heat exposure in early life. The analysis included 2,681 children from the Generation R Study, a birth cohort in Rotterdam, who underwent magnetic resonance imaging (MRI) between 9 and 12 years of age. The MRI protocol assessed brain connectivity by measuring the magnitude and direction of water diffusion within the brain's white matter. In more mature brains, water flows more in one direction than in all directions, which gives lower values for a marker called mean diffusivity and higher values for another marker called fractional anisotropy. The research team used an advanced statistical approach to estimate, for each participant, exposure to monthly mean temperatures from conception until 8 years of age, and their effect on these MRI connectivity parameters (mean diffusivity and fractional anisotropy) measured at 9-12 years.

Susceptibility window between pregnancy and age three

The results show that exposure to cold during pregnancy and the first year of life, and exposure to heat from birth until 3 years of age were associated with higher mean diffusivity at preadolescence, pointing to slower white matter maturation. 'Cold' and 'heat', in this case, are defined as those temperatures that are at the lower and upper end, respectively, of the temperature distribution in the study region.

"The fibres of the white matter are responsible for connecting the different areas of the brain, enabling communication between them. As the white matter develops, this communication becomes faster and more efficient. Our study is like a photograph at a particular moment in time and what we see in that image is that participants more exposed to cold and heat show differences in a parameter -- the mean diffusivity -- which is related to a lower level of maturation of the white matter," explains Laura Granés, IDIBELL and ISGlobal researcher and first author of the study. "In previous studies, the alteration of this parameter has been associated with poorer cognitive function and certain mental health problems," she adds.

"The largest changes in connectivity parameters are observed in the first years of life," says co-author and IDIBELL, UB and CIBERSAM researcher Carles Soriano. "Our results suggest that it is during this period of rapid brain development that exposure to cold and heat can have lasting effects on the microstructure of white matter."

No association was found between temperature exposure in early life and fractional anisotropy at 9-12 years. The authors argue that a possible explanation is that these two metrics reflect different microstructural changes, and that mean diffusivity may be a more robust indicator of white matter maturation, compared to fractional anisotropy.

Poorer children more at risk

A stratified analysis by socioeconomic conditions showed that children living in poorer neighbourhoods were more vulnerable to cold and heat exposure. In these children, the windows of susceptibility to cold and heat were similar than those identified in the overall cohort, but started earlier. These differences may be related to housing conditions and energy poverty.

One important mechanism that could explain the effect of ambient temperature on neurodevelopment could be related to poorer sleep quality. Other possible mechanisms include disruption of placental functions, activation of the hormonal axis leading to higher cortisol production, or inflammatory processes.

"Our findings help to raise awareness of the vulnerability of foetuses and children to changing temperatures," says Guxens. The findings also stress the need of designing public health strategies to protect the most vulnerable communities in the face of the looming climate emergency.