The Role of Maternal Secretor Status and Human Milk Oligosaccharides on Early Childhood Development: A Systematic Review and Meta-Analysis

Breast milk is the gold standard of infant nutrition, delivering nutrients and bioactive molecules as needed to support optimal infant growth and neurodevelopment. Increasing evidence links the human milk oligosaccharides (HMOs) to these early childhood development milestones. In this PRISMA-compliant systematic review and meta-analysis, we summarised evidence on HMOs and infant brain development, physical growth, and cognitive development. In addition, we compared HMO concentrations between secretor and non-secretor mothers. Searches in PubMed, Scopus, and Web of Science yielded 245 articles, 27 of which were included in the systematic review and 12 in the meta-analysis. The meta-analysis revealed a substantial between-study heterogeneity, I2 = 97.3%. The pooled effect was 0.21 (95% CI, −0.41 - 0.83), p = 0.484, indicating that secretors had higher HMO concentrations, though this difference was not statistically significant. At one month of age, 2’FL, 3FL, and 3’SL play an important role in brain maturation and thus play a critical role in cognitive development. Secretors secrete higher concentrations of 2’FL and 3’SL, explaining the benefits to infants of secretor mothers. Growth velocity was correlated to fucosylated and sialylated HMO concentrations, with lower concentrations linked to stunting. In conclusion, evidence from the systematically reviewed articles indicates that HMOs are important for a child’s early development, but the extent to which they have an impact is dependent on maternal secretor status. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The authors received no specific funding for this work. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All the data included was extracted from the selected original articles. The code used for the meta-analysis can be requested from the corresponding author. * 2’FL : 2-fucosyllactose 3FL : 3-fucosyllactose DFLac : difucosyllactose DFLNH : difucosyllacto-N-hexaose DFLNT : difucosyllacto-N-tetraose FLNH : fucosyllacto-N-hexaose LNFP I : lacto-N-fucopentaose I LNFP II : lacto-N-fucopentaose II LNFP III : lacto-N-fucopentaose III 3’SL : 3-sialyllactose 6’SL : 6-sialyllactose DSLNT : disialyllacto-N-tetraose DSLNH : disialyllacto-N-hexaose LST b : sialyllacto-N-tetraose b LST c : sialyllacto-N-tetraose c FDSLNH : fucodisialyllacto-N-hexaose LNH : lacto-N-hexaose LNnT : lacto-N-neotetraose LNT : lacto-N-tetraose