Advanced Understanding of Human Milk Oligosaccharides in Infant Nutrition

A large-scale Chinese analysis quantified 17 major human milk oligosaccharides across six regions and found total HMO concentrations fall sharply in the first 200 days postpartum before stabilizing between 200 and 400 days—results that directly affect lactation counseling, donor-milk selection, and formula benchmarking.

The study expands earlier, smaller cohorts by sampling six Chinese regions and extending the lactation window to 400 days, enlarging the empirical base for HMO exposure across the first year-plus. That extended timeline clarifies when milk provides the densest HMO exposure and when composition becomes comparatively stable, altering the evidentiary baseline clinicians use when advising families.

Total HMO concentration peaks in colostrum and transitional milk, declines through early lactation, then plateaus between days 200 and 400. Several individual HMOs depart from this general downward trend: the oligosaccharide 3-FL rises over the lactation course while the sialylated analogue 3'-SL remains comparatively stable, highlighting HMO-specific temporal heterogeneity. In short, the early postnatal window is relatively HMO-rich for most analytes but not uniformly so across all structures.

Phenotype analysis identified four primary Se/Le groups. The Se+/Le+ phenotype was most common and associated with higher concentrations of fucosylated HMOs, while the double-negative Se-/Le- phenotype correlated with lower overall HMO levels. These differences reflect variable maternal fucosyltransferase and Lewis enzyme activity, which alter the degree of HMO fucosylation and shift the molecular profile of milk. The result is population-level heterogeneity in HMO exposure through breastfeeding.

These temporal and phenotype patterns can inform donor-milk selection, guide timing of fortification strategies for very low–birth-weight infants, and support targeted HMO matching in formula development. Phenotype data may help determine whether donor pools or fortifiers should emphasize fucosylated versus sialylated structures, and timing information can indicate when fortification or formula transitions are most likely to address HMO shortfalls. Overall, the findings favor tailoring nutrition strategies to lactation stage and maternal phenotype rather than assuming a uniform HMO exposure profile.

Key Takeaways:

• What’s new? The study quantifies 17 major HMOs across six Chinese regions and shows a steep decline in total HMO concentration through 200 days with stabilization from 200–400 days.
• Who’s affected? Breastfeeding infants, donor-milk programs, and neonatal nutrition teams—particularly those caring for very low–birth-weight infants—are affected by the documented temporal and phenotype-related HMO variability.
• What changes next? Temporal and Se/Le phenotype data can refine counseling, improve donor-milk matching, and prioritize targeted fortification research.