Early-Life Cumulative Intake of Ultra-Processed Foods and Subcortical Brain Volume at Age Six Years: A Prospective Cohort Study

BACKGROUND: Diet quality during early life may influence neurodevelopmental trajectories, but the associations between ultra-processed food (UPF) intake and neurocognitive outcomes has not been broadly examined. OBJECTIVE: To examine whether cumulative UPF intake from infancy through early childhood is associated with cognitive performance at 24 and 72 months and with subcortical brain volumes at 72 months. METHODS: In this prospective birth cohort study, multiple 24-hour dietary assessments were used to calculate the percentage of UPF-calorie intake, using the Nova classification system. Cumulative UPF intake from 6 to 24 and from 6 to 72 months was summarized as the area under the curve. Cognitive performance was assessed at 24 and 72 months, and subcortical brain volumes were derived from T1-weighted MRI scans at 72 months. Associations were examined using multiple univariate linear regressions with false discovery rate (FDR) correction. RESULTS: Cumulative UPF intake was not associated with cognitive performance at either 24 months (n=144, 57% girls) or 72 months (n=93, 59% girls). In contrast, cumulative UPF intake from 6 to 72 months (n=79, 58% girls) was inversely associated with the volumes of the bilateral accumbens, left amygdala, bilateral pallidum, left putamen, and bilateral thalamus (all FDR-adjusted p < 0.05). On average, a 10% higher proportion of cumulative UPF intake was associated with a 1.92% lower subcortical volume (CI95% -3.29, -0.58). Associations were consistent across exposure windows (6-24 months compared with 72 months) and UPF subtypes (e.g., snacks, fast food). CONCLUSIONS: Greater cumulative UPF intake from infancy through early childhood was associated with differences in neurodevelopment at age six years. These findings highlight this period as a potentially relevant window for nutrition-focused prevention efforts. Future studies are needed to clarify specific windows, neurobiological mechanisms, identify specific nutritional factors, and define long-term implications.