Infancy is a critical period for neurodevelopment, which includes myelination, synaptogenesis, synaptic pruning, and the development of motor, social-emotional, and cognitive functions. Human milk provides essential nutrients to the infant’s developing brain, especially during the first postnatal months. Human milk oligosaccharides (HMOs) are a major component of human milk, and there is growing evidence of the association of individual HMOs with cognitive development in early life. However, to our knowledge, no study has explained these associations with a mechanism of action. Here, we investigated possible mediating associations between HMOs in human milk, brain myelination (measured via myelin water fraction), and measures of motor, language (collected via the Bayley Scales of Infant and Toddler Development (Bayley-III)), and socioemotional development (collected via the Ages and Stages Questionnaire: Social-Emotional Version (ASQ-SE)) in healthy term-born breast-fed infants. The results revealed an association between 6′Sialyllactose and social skills that was mediated by myelination. Furthermore, associations of fucosylated HMOs with language outcomes were observed that were not mediated by myelination. These observations indicate the roles of specific HMOs in neurodevelopment and associated functional outcomes, such as social-emotional function and language development.

Background and objectives: Oral Nutritional Supplements (ONS) is shown to impact growth in nutritionally at-risk children, however, effects on developmental progress and behavior are not well elucidated. We aimed to assess the effect of ONS combined with dietary counselling (DC) on the achievement of developmental skills, temperament traits, and parent-reported toddler quality of life in 1–3-year-old children in the ≤25th weight-for-length percentile. Methods: In this prospective single-arm, open-label intervention study (N = 108), Filipino children received 2 servings/day of ONS, plus DC for 16 weeks. The ONS was energy and nutrient dense with increased levels of vitamin A, iron, and zinc (growth-limiting micronutrients), as well as DHA and phospholipids, including sphingomyelin. Developmental milestone achievement, temperament traits, and toddler health-related quality of life scores were assessed using the Ages and Stages Questionnaire (ASQ-3), Early Childhood Behavior Questionnaire (ECBQ-SF), and Infant and Toddler Quality of Life Questionnaire Short Form (ITQOL-SF47), respectively, at both baseline and week 16. Change scores were analyzed by ANCOVA, correcting for baseline measure, age, and sex. Results: The children´s mean age at baseline was 21.3 ± 6.6 months and 44.4% were male. There was a significant increase (p < 0.01 for all) in scores for language, motor, cognitive, and social developmental domains from baseline to week 16. Temperament scores related to social skills and behavioral regulation including cuddliness, high intensity pleasure, low intensity pleasure, perceptual sensitivity, positive anticipation, sociability, surgency, and effortful control all increased significantly (p < 0.05 for all) from baseline to week 16. The scores on several parent-reported aspects of child well-being such as satisfaction with their child’s growth and development (including physical growth, motor and language development, responsiveness to others, and learning abilities), their child’s overall behavior (including the ease of managing it), their child getting along with others (including less tantrums, responding positively to affection, and listening and following directions), and their child’s health increased significantly (p < 0.05 for all) from baseline to week 16. Conclusion: ONS combined with DC in toddlers experiencing growth concerns supports developmental skills and temperament traits essential for learning, as well as parent-perceived toddler quality of life.