Sex-dependent associations between human milk oligosaccharides and malaria outcomes in breastfeeding Ugandan children

Human milk oligosaccharides (HMOs), whose compositions vary between secretor and non-secretor mothers, protect breastfeeding children against various diseases. We investigated the relationship between HMOs in Ugandan secretor mothers and malaria outcomes in their children. Malaria outcomes in breastfeeding children followed up over seven months were classified as malaria-free and asymptomatic, mild, or severe malaria. A single human milk sample collected from each mother was analyzed for HMOs. Significantly higher 2-fucosyllactose (2FL) and lacto-N-fucopentaose I (LNFP I) concentrations were observed in mothers of malaria-free children, and significantly higher lacto-N-tetraose (LNT) concentrations were observed in mothers of children with asymptomatic malaria. Concentrations of five HMOs, 3-fucosyllactose (3 FL), 3-sialyllactose (3SL), difucosyllactose (DFLac), lacto-N-fucopentaose II (LNFP II), and sialyllacto-N-tetraose b (LSTb); and two HMOs, difucosyllacto-N-tetrose (DFLNT) and fucosyllacto-N-hexaose (FLNH) were significantly higher in mothers of malaria-infected children and children with severe malaria, respectively. Sex-dependent associations were observed for some HMOs. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by Global Innovation Fund and Grand Challenges Canada ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Uganda National Council for Science and Technology and the Research Ethics Committee of the Vector Division, Ministry of Health, approved the original HD4MC study. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the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 data produced in the present study are available upon reasonable request to the authors