In utero air pollution exposure and pre- and postnatal brain development: a review

Air pollution is a major threat to public health globally and may also adversely influence brain development. Key neurodevelopmental processes unfold within narrow and sensitive windows during fetal life and continue through childhood and adolescence, leaving the brain particularly vulnerable to environmental influences. Prenatal air pollution exposure could possibly disrupt fetal neurodevelopmental processes via direct placental crossing of pollutants or through maternal inflammatory processes. This literature review evaluates evidence from ultrasound and MRI studies examining associations of in utero air pollution exposure (particulate matter (PM₁₀ (≤10 μm), PM_coarse (10 - 2.5 μm), PM_2.5 (≤2.5 μm), PM characteristics (PM composition and oxidative potential)), nitrogen oxides (NO_x), sulfur dioxide (SO₂), carbon monoxide (CO), black carbon, and ozone (O₃)) with structural brain development from the fetal period through adolescence. Findings are summarized per pollutant to evaluate potential adverse effects of individual pollutants in the complex mixture of air pollution. Results indicate associations between in utero air pollution exposure and structural brain outcomes, although no distinct patterns or differences between individual pollutants could be identified. Prenatal ultrasound studies reported negative associations between in utero air pollution exposure levels and the global fetal brain metrics biparietal diameter and head circumference in geographical regions with relatively high air pollution levels. In contrast, childhood and adolescent MRI studies, mainly conducted in relatively low exposure areas, showed no associations with global brain volumes. However, associations with regional brain measures were reported including changes in cerebral cortex regions, subcortical gray matter structures, and global and regional white matter structures, potentially impacting cognitive and behavioral outcomes in childhood. Overall, current evidence supports a link between prenatal air pollution and altered brain development, highlighting the need for longitudinal and mechanistic studies to clarify causal pathways and functional consequences.