Sex differences in the associations of human milk oligosaccharides with height and weight in breastfed Ugandan children

Background & ObjectiveHuman milk oligosaccharides (HMOs) have been associated with several child growth metrics, but there was no difference in the associations according to child sex. Here, we present clinic-based cross-sectional data on the relationship between specific HMOs in the milk of Ugandan mothers and growth in their breastfed children as a group and as males and females separately. MethodHuman milk samples were manually collected from 127 lactating mothers. Levels of human milk oligosaccharides (HMOs) were analyzed by high-performance liquid chromatography (HPLC). Childrens weight and length were measured using a portable digital scale and length board, respectively. Weight-for-age (WAZ), height-for-age (HAZ) and weight for height (WHZ) Z scores were calculated. The relationships between HMOs and untransformed weights and heights and between WAZ, HAZ and WHZ subcategories were analyzed for all children and for males and females separately by Spearmans correlation and Kruskal-Wallis and Mann-Whitney U tests. ResultsThere were positive and negative correlations between the concentrations of specific HMOs and the heights and weights of children according to mothers secretor status. Tall infant stature was associated with higher concentrations of 6SL, LSTc, DFLNH, DSLNH, LNnT and total HMOs in secretor or nonsecretor mothers; short infant stature was associated with higher concentrations of 3FL and DFLac; overweight was associated with higher concentrations of 6SL, LSTc and LNnT in secretor and nonsecretor mothers; and normal weight was associated with higher concentrations of 3FL. The associations between maternal HMO levels and childrens heights and weights or between the LAZ, WAZ and WHZ subcategories significantly differed between male and female children. ConclusionsThere are sex differences in the associations between high concentrations of some HMOs and stature and weight in Ugandan children born to secretor and nonsecretor mothers. HighlightsO_LIThis study showed that some HMOs are associated with child growth metrics in a sex-specific pattern. C_LIO_LIFour HMOs (3FL, DSLNT, DFLac, and 3SL) were positively correlated with the height/length of the children. C_LIO_LIThere were significant positive correlations between height/length and 3FL and DSLNT in only female children and between height/length and DFLac in only male children. C_LIO_LIDSLNT, DFLac and LSTb were positively correlated with weight in female and male children respectively. C_LI Plain Language SummaryHuman milk oligosaccharides (HMOs) have been associated with growth parameters of children in the Americas, Europe and Asia. Only two such studies have been conducted in Africa. None of the studies investigated the relationship between child sex and HMO composition and growth interactions. We examined the relationship between 19 well-characterized HMOs and growth metrics and also dissected the data by infant sex. Our results show a positive correlation between some HMOs and growth indices in either female or male children only. This highlights the impact of sex differences in the relationship between specific HMOs and growth measures in children. This evidence, if validated, could inform future nutritional interventions involving combinations of HMOs as food supplements that are equally effective for both male and female children.