4. Discussion
Sleep behaviors, well-nourished, Gray matter volume
RECRUITMENT
These clinical trial findings, in addition to the previously reported 3- and 6-month data [Myelination is a hallmark of neurodevelopment and critical for information processing, cell communication, and brain plasticity important for learning and development [Gray matter volume develops rapidly in early childhood. A longitudinal observational study showed that cortical gray matter volume increases by 106% in the first year of life and 18% in the second year of life, with association cortices growing particularly rapidly in the first year and frontal and parietal regions growing quickly in the second year of life [The behavioral impact of the nutritional intervention in this study was most consistent for sleep outcomes and aspects of sociability, which are age-appropriate development domains in children of that age. Sleep behaviors mature rapidly in the first year of life, and a lower number of night awakenings as well as longer daytime naps in infants have been linked to better memory performance [Our study shows that myelin imaging is a relevant and objective marker for brain growth and associated functional outcomes in a preverbal population of neurotypical children. Our findings are in line with the suggested age-specific relationship between structure and cognition [Strengths of the study include the longitudinal RCT design, including objective measures of brain development from neuroimaging, which strengthens nutritional research in early life. Myelin imaging has been shown to be a viable and relevant proxy for brain development that can be used to assess the impact of nutrition on brain structure and architecture. For future RCTs, it is desirable to further reduce the brain imaging protocol; additional sequences on structural and functional connectivity did not result in sufficient analyzable data in our study population, and the myelin imaging sequence was most successful in that age group.Limitations include the impact of the COVID-19 pandemic on recruitment and retention, resulting in a smaller sample size than expected, in particular for later visits. The low sample size impacted the analyses and conclusion on intervention effects related to cognitive and behavioral outcomes. In addition, the investigational exploratory nature of the study requires cautious interpretation of the inferential statistics, as type I and type II errors are uncontrolled. To mitigate this, the number of computed Overall, our findings add important insights into early brain architecture and behavioral development in a population where nutritional intervention studies are still scarce. They highlight an opportunity to improve developmental (i.e., de novo) myelination, a critical process in learning and development, as well as gray matter development and aspects of sleep and sociability in healthy, well-nourished infants via a nutritional intervention with levels and combinations of nutrients that were selected based on scientific evidence of their role in myelination.