Age-dependent associations of human milk oligosaccharides with body size and composition up to 4 years of age

Am J Clin Nutr. 2023 May;117(5):930-945. doi: 10.1016/j.ajcnut.2023.02.016. Epub 2023 Feb 21.


Background: Human milk oligosaccharides (HMOs) are major components of human milk that may mediate its beneficial effects on infant growth.

Objectives: To investigate relationships between HMO concentrations in milk at 6 wk postpartum and anthropometry to 4 y of age in human milk-fed infants.

Methods: Milk samples were collected from 292 mothers at 6 wk (median 6.0 wk; range 3.3, 11.1] postpartum in a longitudinal, population-derived cohort. Of the infants, 171 were exclusively human milk-fed to 3 mo of age and 127 to 6 mo. Concentrations of 19 HMOs were quantified using high-performance liquid chromatography. Maternal secretor status (n = 221 secretors) was determined from 2'-fucosyllactose (2'FL) concentration. We calculated z-scores for child weight, length, head circumference, summed triceps and subscapular skinfold thicknesses, and weight-for-length at 6 wk, 6 mo, 12 mo, and 4 y. We investigated associations of secretor status and each HMO measure with change from birth for each z-score using linear mixed-effects models.

Results: Maternal secretor status was not associated with anthropometric z-scores up to 4 y of age. Several HMOs were associated with z-scores at 6 wk and 6 mo, predominantly within secretor status subgroups. Higher levels of 2'FL were associated with greater weight [β = 0.91 increase in z-score per SD increase log-2'FL, 95% CI (0.17, 1.65)] and length [β = 1.22, (0.25, 2.20)] in children born to secretor mothers, but not body composition measures. Higher lacto-N-tetraose was associated with greater weight [β = 0.22, (0.02, 0.41)] and length (β = 0.30, (0.07, 0.53)] among children born to nonsecretor mothers. Several HMOs were associated with anthropometric measures at 12 mo and 4 y of age.

Conclusions: Milk HMO composition at 6 wk postpartum is associated with several anthropometry measures up to 6 mo of age in a potential secretor status-specific manner, with largely different HMOs associating with anthropometry from 12 mo to 4 y of age.

Keywords: 2’FL; adiposity; anthropometry; growth; human milk oligosaccharides; secretor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Body Size
  • Child
  • Female
  • Humans
  • Infant
  • Milk, Human* / chemistry
  • Mothers
  • Oligosaccharides* / analysis
  • Postpartum Period


  • Oligosaccharides