The two-centre randomised controlled trial (RCT) funded by Société des Produits Nestlé S.A., investigated the effect of a 12-month nutritional intervention on longitudinal changes in myelination (the formation of the myelin sheath around a nerve to allow for improved conduction), cognition, and behaviour, in 81 healthy infants.
They supplemented children with a placebo or a blend of DHA, ARA, iron, vitamin B12, folic acid, and sphingomyelin from a whey protein concentrate enriched in alpha-lactalbumin and phospholipids.
Results displayed significantly higher myelination in the supplemented group, compared to the control, at six, 12, 18, and 24 months of life, as well as significantly higher grey matter volume (which contains neurons and synapses) at 24 months.
Supplementation was also associated with a reduced number of night awakenings at six months, increased day sleep at 12 months, and reduced social fearfulness at 24 months.
The authors from Switzerland, Ireland, and the US, conclude: “Findings add important insights into early brain architecture and behavioural development in a population where nutritional intervention studies are still scarce.
“They highlight an opportunity to improve developmental myelination, a critical process in learning and development, as well as grey matter development and aspects of sleep and sociability in healthy, well-nourished infants via a nutritional intervention with levels and combinations of nutrients.”
Several nutritional components of breast milk have been associated with neurodevelopmental outcomes in infants and young children, including long-chain polyunsaturated fatty acids (LC-PUFA; e.g., docosahexaenoic acid (DHA) and arachidonic acid (ARA)) and micronutrients.
Recent systematic reviews in healthy infants have shown the positive effects of LC-PUFA (e.g., DHA and ARA) on cognitive functions, however according to the authors of the new study they reported no effect of protein level modifications in infant formulas on cognitive development, and beneficial short-term effects of MFGM components.
The authors explain: “While there are many factors and mechanisms that play a role in the link between early life nutrition and cognitive or behavioural development, de novo myelination has shown both relevance and feasibility in researching that relationship.”
Previous research has shown that of a blend of DHA, ARA, vitamin B12, folic acid, iron, and sphingomyelin (SM), increased the number, differentiation, and maturation of oligodendrocyte precursor cells on myelin mechanisms in a primary cell culture model.
Results from a previous statistical analysis of the first two completed time points in a randomised controlled trial testing the same blend of nutrients in neurotypical infants showed increased brain myelination at three and six months of life in an investigational group compared to control.
The authors aimed to extend this research to report the longitudinal results of brain, cognitive, and behavioural changes up to 24 months, noting: “This the first nutritional intervention study in term infants to explore the effect of a blend of nutrients on myelination, a process that is critical for cognitive development and learning.”
“Observational data from birth cohorts exploring trajectories of white matter maturation using myelin water imaging, suggest a general trend of a steep increase in myelin in the first two years of life and a shoulder point at around two years that is followed by continued but less steep increase in myelin.”
They hypothesised that 12-month supplementation with their nutritional blend in neurotypical term-born children, would increase myelination over the first two years of life.
189 participating infants (mean age 29.9 (±7.45) days) were randomised into one of two intervention groups, either receiving the supplemental milk-based formula or a control formulation. Non-randomized breastfed children (108 (57.1%)) served as a natural reference group.
Result data from myelin-sensitive MRI sequences showed significantly higher levels of myelin for the investigational versus the control group: Effects were found for the whole-brain myelin water fraction (MWF) at six months (+0.007, 95% CI [+0.0012; +0.0126]; p = 0.018), 12 months (+0.012, 95% CI [+0.0045; +0.0189]; p = 0.002), 18 months (+0.012, 95% CI [+0.0052; +0.018]; p ≤ 0.001), and 24 months (+0.018, 95% CI [+0.0086; +0.0264]; p ≤ 0.001)
The supplemented group also showed a significant reduction in night awakenings at six months compared to the control group and an increase in day sleep at 12 months as well as a significant decrease in the social fearfulness subscale of the TBAQ at 24 months.
The authors state: “Correlational analyses between myelin, grey matter, and developmental outcomes strengthen the observations on sleep effects and demonstrate a link between first-year myelination and motor development at one year of life.
“Myelination is a hallmark of neurodevelopment and critical for information processing, cell communication, and brain plasticity important for learning and development. Our findings add to previous observations displaying a steep increase in myelin during the first two to three years of life by showing that a specific blend of nutrients can support that trajectory.”
The note limitations to the study, including the impact of the Covid-19 pandemic on recruitment and retention, which resulted in a smaller sample size than expected.
“Impact of a Nutrient Formulation on Longitudinal Myelination, Cognition, and Behavior from Birth to 2 Years: A Randomized Clinical Trial.”
Authors:Nora Schneider, Mickaël Hartweg, Jonathan O’Regan, Jennifer Beauchemin, Leanne Redman, Daniel S. Hsia, Pascal Steiner, Owen Carmichael, Viren D’Sa and Sean Deoni.