Sex-specific impact of early nutrition on neurodevelopment, cognition and brain structure in healthy children up to 6-year-old: Findings from the COGNIS study

Background early nutrition plays a critical role in brain development, but the potential combined effects of sex and nutrition are still relatively understudied. Objective to explore whether sex can influence the long-term impact of early nutrition on neurodevelopment, cognitive function, and brain structure in healthy infants up to 6 years old. Methods the current study involved healthy children up to 6 years old participating in the COGNIS Study. Infants were randomized to receive, during their first 18 months of life, a standard (SF) or an experimental infant formula (EF) enriched with bioactive nutrients including long-chain polyunsaturated fatty acids (LC-PUFAs), milk fat globule membrane (MFGM) and synbiotics, among others. As a reference group, breastfed (BF) children were included. A total of 108 children, were followed-up to 6 years old (SF, n = 37; EF, n = 39; BF, n = 32). Results girls presented better cognitive development at 18 months of life and better execution in a Go/no-Go task at 6 years old, while boys showed better reaction time at 6 years. Girls showed greater regional brain volumes in temporal lobes. Boys presented greater cortical thickness in posterior brain areas, while girls had greater cortical thickness in cingulate and frontal areas. Additionally, EF fed boys showed higher intelligence quotient (IQ), as well as better long-term verbal memory than SF fed boys. EF boys also presented higher volumes in different regions of the right parietal lobule, and lower cortical thickness in right frontal sulcus, compared to SF boys. Finally, higher volumes and lower cortical thickness of different brain areas, particularly in girls, were associated with better cognitive development. Conclusions our findings suggest that infant formula enriched with bioactive nutrients may exert long-term, sex-specific beneficial effects on neurocognitive development and brain structure, particularly in boys. These results underscore the potential importance of developing sex-specific nutritional interventions during early life to optimize neurodevelopmental outcomes.