Human milk 3'-Sialyllactose is positively associated with language development during infancy

Seoyoon Cho, Ziliang Zhu, Tengfei Li, Kristine Baluyot, Brittany R. Howell, Heather C. Hazlett, Jed T. Elison, Jonas Hauser, Norbert Sprenger, Di Wu, Weili Lin

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


BACKGROUND: Genetic polymorphisms leading to variations in human milk oligosaccharide (HMO) composition have been reported. Alpha-Tetrasaccharide (A-tetra), an HMO, has been shown to only be present (>limit of detection; A-tetra+) in the human milk (HM) of women with blood type A, suggesting genetic origins determining the presence or absence (A-tetra-) of A-tetra in HM.

OBJECTIVES: This study aimed to determine whether associations exist between HMO concentrations and cognitive development, and whether the associations vary between A-tetra+ and A-tetra- groups in children (<25 months old).

METHODS: We enrolled typically developing children (2-25 months old; mean, 10 months old) who were at least partially breastfed at the study visit. The Mullen Scales of Early Learning (MSEL) were used as the primary outcome measure to assess early cognitive development. Linear mixed effects models were employed by stratifying children based on A-tetra levels (A-tetra+ or A-tetra-) to assess associations between age-removed HMO concentrations and both MSEL composite scores and the 5 subdomain scores.

RESULTS: A total of 99 mother-child dyads and 183 HM samples were included (A-tetra+: 57 samples, 33 dyads; A-tetra-: 126 samples, 66 dyads). No significant association was observed between HMOs and MSEL when all samples were analyzed together. The composite score and 3'-sialyllactose (3'-SL) levels were positively associated [P = 0.002; effect size (EF), 13.12; 95% CI, 5.36-20.80] in the A-tetra + group. This association was driven by the receptive (adjusted P = 0.015; EF, 9.95; 95% CI, 3.91-15.99) and expressive (adjusted P = 0.048; EF, 7.53; 95% CI, 2.51-13.79) language subdomain scores. Furthermore, there was an interaction between 3'-SL and age for receptive language (adjusted P = 0.03; EF, -14.93; 95% CI, -25.29 to -4.24).

CONCLUSIONS: Our study reports the association of 3'-SL and cognition, particularly language functions, in typically developing children who received HM containing detectable A-tetra during infancy.

Original languageEnglish (US)
Pages (from-to)588-597
Number of pages10
JournalAmerican Journal of Clinical Nutrition
Issue number2
StatePublished - May 21 2021

Bibliographical note

Funding Information:
This study was supported in part by NIH grants (U01MH110274 to WL and JTE; R01MH104324 and MH1044324-03S1 to JTE; MH015755 to BRH?s trainee) and a grant from Nestl? Product Technology Center-Nutrition, Soci?t? des Produits Nestl? SA, Switzerland (to WL).

Publisher Copyright:
© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.


  • breastfed infants
  • early cognitive development
  • human milk
  • human milk oligosaccharides
  • language
  • Mullen Scales of Early Learning
  • random linear mixed effects model
  • sialyllactose
  • Oligosaccharides/chemistry
  • Humans
  • Language Development
  • Breast Feeding
  • Child, Preschool
  • Infant
  • Milk, Human/chemistry
  • Adult
  • Female

PubMed: MeSH publication types

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


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