A Positive Correlation between Breast Milk 3’-Sialyllactose and Language Development during Early Infancy - Prof. Weili Lin

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A growing body of research, primarily through animal studies, has suggested that specific human milk oligosaccharides (HMOs), such as 2’-Fucosyllactose (2’FL), 3’-Sialyllactose (3’SL) and 6’-Sialyllactose (6’SL), may have a positive effect on neurodevelopment and cognitive ability. By leveraging the UNC/UMN Baby Connectome Project (BCP), an accelerated longitudinal cohort study designed to quantitatively map brain functional and structural development in typically developing children 0-5 years of age, and the BCP-Enriched study, an ancillary study with expanded scopes to explore nutritional impacts on early brain development, we aimed to determine whether correlations exist between specific HMOs and cognitive development in early childhood.

Methods: A group of healthy children (n=99) in several sequential longitudinal and cross-sectional cohorts who were breastfed at the time of study visits (mean age = 9.88 months, ranging 2.9 – 24.3 months) were included in this analysis. The Mullen Scales of Early Learning (MSEL) was administered to assess the child’s cognitive development, with data points available for each month within the age range. The concurrent breast milk samples (n=191) were obtained and analyzed for specific HMOs including 2’FL, 3’FL, 3’SL, 6’SL, Lacto-N-tetraose (LNT), Lacto- N-neotetraose (LNNT), Lacto-N-fucopentaose I (LNFPI), and A-tetrasaccharide (A-Tetra). To assess the potential associations between HMOs and MSEL scores, age effects of all HMOs were removed first using spline regression, and then a log-transformation was applied for 3’SL to minimize heteroskedasticity and satisfy the linear assumption of a linear model. The associations between age-adjusted HMOs and concurrently collected age-adjusted MSEL (as the response variable) was tested using a random linear mixed effects model with both the child IDs and examiner IDs as random effects. The potential batch and study site effects were also controlled. 

Results: HMOs were quantified in all breast milk samples, except for A-Tetra which was undetectable in 129 samples from 68 mothers, and 44 samples from 19 subjects with 2’FL <11 mg/L. Specific HMOs (3’FL and 3’SL) positively and others (2’FL, LNT, LNNT, 6’SL and LNFPI) negatively associated with age. More importantly, age-adjusted 3’SL was positively associated with Receptive (partial correlation coefficient r=0.28, p<0.03) and Expressive (r=0.399, p<0.005) language t-scores in the subset with detectable A-Tetra. No correlation between age-adjusted 3’SL and any of the MSEL subscale scores was detected in the subset of undetectable A-Tetra. No other associations were detected between age-adjusted HMOs and MSEL scores.

Conclusion: To the best of our knowledge, this is the first study reporting positive associations between sialylated HMOs and language development in early childhood. The results also indicated that interactions between specific HMOs may influence their effect on early cognitive development. Further research into the underlying biological mechanisms is warranted.


Prof. Weili Lin

Prof. Weili Lin

University of North Carolina at Chapel Hill, Chapel Hill, USA

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