1. Introduction
reduced social fearfulness, term-born, gray matter volume
Observation studies suggest differences in myelination in relation to differences in early life nutrition. This two-center randomized controlled trial investigates the effect of a 12-month nutritional intervention on longitudinal changes in myelination, cognition, and behavior. Eighty-one full-term, neurotypical infants were randomized into an investigational (N = 42) or a control group (N = 39), receiving higher versus lower levels of a blend of nutrients. Non-randomized breastfed infants (N = 108) served as a reference group. Main outcomes were myelination (MRI), neurodevelopment (Bayley-III), social-emotional development (ASQ:SE-2), infant and toddler behavior (IBQ-R and TBAQ), and infant sleep (BISQ) during the first 2 years of life. The full analysis set comprised N = 67 infants from the randomized groups, with 81 myelin-sensitive MRI sequences. Significantly higher myelination was observed in the investigational compared to the control group at 6, 12, 18, and 24 months of life, as well as significantly higher gray matter volume at 24 months, a reduced number of night awakenings at 6 months, increased day sleep at 12 months, and reduced social fearfulness at 24 months. The results suggest that brain development may be modifiable with brain- and age-relevant nutritional approaches in healthy infants and young children, which may be foundational for later learning outcomes.Nutrition plays an important role in brain development and learning, particularly during the period of rapid growth in the first years of life [While there are many factors and mechanisms that play a role in the link between early life nutrition and cognitive or behavioral development, de novo myelination has shown both relevance and feasibility in researching that relationship. In past work, we demonstrated the effect of a blend of DHA, ARA, vitamin B12, folic acid, iron, and sphingomyelin (SM) on myelin mechanisms in a primary cell culture model, including an increase in the number, differentiation, and maturation of oligodendrocyte precursor cells [In this randomized controlled investigational trial, we tested the hypotheses that 12-month supplementation with a blend of DHA, ARA, iron, vitamin B12, folic acid, and sphingomyelin from a uniquely processed whey protein concentrate enriched in alpha-lactalbumin and phospholipids in neurotypical term-born children increases myelination over the first 2 years of life.