How Human Milk Oligosaccharides Drive Neurodevelopment

A guide to early infant neurodevelopment

New research has shown that brain development in infants depends on Human Milk Oligosaccharides (HMOs) and epigenetic mechanisms [2,3,5,7]. Current findings published in the MDPI Special Issue on Infant Feeding & Neurodevelopment, as well as the Nestlé Nutrition Institute, explore the topic in detail ^[2,5].

Human milk oligosaccharides (HMOs) and cognitive development

Information in the MDPI Special Issue suggests that specific Human Milk Oligosaccharides (HMOs), particularly sialylated and fucosylated structures, may support early brain development by modulating pathways involved in cognition, memory, and neural signalling ^[2,5].

Recent reviews further link early HMO exposure with improved cognitive outcomes, potentially through the actions of sialic acid and fucose, key substrates for neurodevelopment ^[2,5]. These findings extend the well-established view that HMOs, the third most abundant solid component of human milk, support gut maturation and immune protection, with cognitive benefits now emerging as an additional area of interest ^[2,5].

Advances in nutritional science have also enabled the inclusion of select HMOs, such as 2’-FL and LNnT, in some infant nutrition solutions ^[2,5].

Epigenetics: How human milk influences gene expression

A 2023 review in Nutrients (Gialeli et al.) describes how bioactive components of human milk, including microRNAs, long non-coding RNAs, stem cells, and the milk microbiome, may influence gene regulation relevant to brain development ^[3]. Notably, some of these factors may withstand digestion, enter systemic circulation, and potentially interact with the central nervous system (including via the blood-brain barrier), thereby affecting pathways that support neural maturation and cognitive function ^[3,7].

Feeding practices & neurodevelopment

Insights from the Nestlé Nutrition Institute indicate that early feeding practices, from exclusive breastfeeding to timely, high-quality complementary feeding, can meaningfully influence long-term health and developmental trajectories ^[1,2,5,8]. Breastmilk’s lower protein content, alongside optimised weaning practices, may help reduce the risk of later obesity and support healthier lifelong outcomes ^[1,2].

Why does this matter?

Early infancy is a critical window for brain development, during which nutrition, environment and biology shape lifelong cognitive, motor and socio-emotional outcomes [1,8]. Recent research underscores the scale and urgency of this period. A large Swedish national cohort study (2024; >1.2 million children; median follow-up 13.1 years) reported 47.8 neurodevelopmental impairment diagnoses per 10 000 person-years, spanning motor, cognitive, epileptic, visual and hearing impairments; risks were higher for infants born moderately and late preterm (HR 1.73 and 1.30 vs term) ^[6].

Globally, The Lancet estimates 250 million children (43% of under-fives in low- and middle-income countries) are at risk of not reaching developmental potential due to stunting and poverty ^[1,8]. From 1990 to 2021, trends show mixed progress, ASD prevalence rising slightly, ADHD declining modestly, and intellectual developmental disorders decreasing more substantially, yet persistent inequities remain, with higher detected ASD prevalence in higher-income settings ^[4].

Longitudinal studies also indicate that neuroimaging biomarkers can emerge within the first year, and scalable assessment metrics are now being validated across several countries, including in regions relevant to ESAR ^[1,4,5]. With brain weight tripling by age two (to ~80% of adult size), early development is especially sensitive to nutrient adequacy, particularly iron, which is essential for cognitive and neurobehavioural development ^[1,2].

Practical applications for parents

Supporting neurodevelopment in infancy does not require complex interventions. Small, consistent everyday behaviours can make a meaningful difference to a child’s developmental trajectory ^[1,8]. Evidence-aligned, parent-friendly strategies include:

Feed responsively: Encourage parents to respond promptly and warmly to hunger and fullness cues. Eye contact, smiles and a calm voice support emotional security. Letting the baby set the pace, without pressure to “finish”, helps build positive feeding experiences ^[1,2,8].

Strengthen connection through interaction: Recommend talking, singing and reading every day, alongside simple face-to-face play, copying sounds and expressions, and naming objects during routines. Skin-to-skin contact can further support bonding and emotional regulation ^[1,8].

Support nutrition from the start: Where possible, promote exclusive breastfeeding for the first 6 months, then introduce iron-rich complementary foods from around 6 months, such as meat, pulses or legumes, and fortified cereals ^[1,2,5,8].

Establish safe, predictable routines: Regular sleep patterns and calm bedtime rituals provide helpful structure. Encourage frequent tummy time to support motor development and advise limiting screen time in favour of real-world play and interaction ^[1,8].

Track milestones and act early: Encourage parents to monitor communication, movement and social engagement milestones, and to seek advice early if concerns arise, particularly for babies born preterm ^[1,6,8].

Closing thoughts

As new scientific understanding unfolds, our shared mission as healthcare professionals remains clear: to promote optimal infant development through evidence-based nutrition, education, and innovation ^[1,2,5,8].

We hope this month’s focus provides meaningful insight into the profound power of early feeding and the emerging science guiding best practices in infant health ^[1,2,5,8].

References

1.    Black, M. M., Walker, S. P., Fernald, L. C. H., Andersen, C. T., DiGirolamo, A. M., Lu, C., & The Lancet Early Childhood Development Series Steering Committee. (2017). Early Childhood Development Coming of Age: Science Through the Life Course. The Lancet, 389(10064), 77–90.
2.    Fan, X., Foster, J., & colleagues. (2025). Advances in Infant and Pediatric Feeding and Nutrition. Nutrients, 17(14), 2378. https://doi.org/10.3390/
3.    Gialeli, G., Panagopoulou, O., Liosis, G., & Siahanidou, T. (2023). Potential Epigenetic Effects of Human Milk on Infants’ Neurodevelopment. Nutrients, 15(16), 3614. https://doi.org/10.3390/nu15163614
4.    Jia, T., Kong, Y., Zhao, G., & Wang, Y. (2025). Trends and Cross-Country Inequalities in the Global Burden of Neurodevelopmental Disorders Among Children Aged 0–14 From 1990 to 2021. Frontiers in Public Health, 13. https://doi.org/10.3389/fpubh.2025.1609254
5.    MDPI. (2025). Special Issue: Early Nutrition and Neurodevelopment. Nutrients. https://www.mdpi.com/journal/nutrients/special_issues/4D1C88SOD9
6.    Mitha, A., Chen, R., Razaz, N., Johansson, S., Stephansson, O., Altman, M., & Bolk, J. (2024). Neurological Development in Children Born Moderately or Late Preterm: National Cohort Study. BMJ, 384, e075630. https://doi.org/10.1136/bmj-2023-075630
7.    News Medical. (2023). The Relationship Between Breast Milk Feeding and Infants’ Neurodevelopment via Epigenetics. Nutrients Review Summary. Retrieved from https://www.news-medical.net/
8.    World Bank. (2024). Early Childhood Development Overview. https://www.worldbank.org/en/topic/earlychildhooddevelopment