Background: Developmental processes in the placenta and the fetal brain are shaped by the same biological signals. Recent evidence suggests that adaptive responses of the placenta to the maternal environment may influence central nervous system development.

Objectives: We studied the association between in utero exposure to fine particle air pollution with a diameter ≤ 2.5 μm (PM_2.5) and placental expression of genes implicated in neural development.

Methods: Expression of 10 target genes in the brain-derived neurotrophic factor ( BDNF ) signaling pathway were quantified in placental tissue of 90 mother–infant pairs from the ENVIR ON AGE birth cohort using quantitative real-time polymerase chain reaction. Trimester-specific PM_2.5 exposure levels were estimated for each mother’s home address using a spatiotemporal model. Mixed-effects models were used to evaluate the association between the target genes and PM_2.5 exposure measured in different time windows of pregnancy.

Results: A 5-μg/m³ increase in residential PM_2.5 exposure during the first trimester of pregnancy was associated with a 15.9% decrease [95% confidence interval (CI): –28.7, –3.2%, p = 0.015] in expression of placental BDNF at birth. The corresponding estimate for synapsin 1 ( SYN1 ) was a 24.3% decrease (95% CI: –42.8, –5.8%, p = 0.011).

Conclusions: Placental expression of BDNF and SYN1 , two genes implicated in normal neurodevelopmental trajectories, decreased with increasing in utero exposure to PM_2.5. Future studies are needed to confirm our findings and evaluate the potential relevance of associations between PM_2.5 and placental expression of BDNF and SYN1 on neurodevelopment. We provide the first molecular epidemiological evidence concerning associations between in utero fine particle air pollution exposure and the expression of genes that may influence neurodevelopmental processes.