Associations between human milk oligosaccharide concentrations and child growth in a Nicaraguan birth cohort

Abstract Human milk oligosaccharides (HMOs) are bioactive components in human milk that influence infant health, yet their role in growth trajectories remains unclear. This study examined associations between concentrations of individual HMOs and child growth outcomes: length-for-age (LAZ), weight-for-age (WAZ), and weight-for-length (WLZ) z-scores—at 24 months of age in a population-based cohort from León, Nicaragua. Data were analyzed from 295 mother–infant dyads. HMO concentrations in human milk collected one month postpartum were measured using high-performance liquid chromatography with fluorescence detection. Infant growth was assessed at 10–14 days, 6, and 24 months, with z-scores calculated per WHO standards. Associations between HMOs and growth outcomes were estimated using generalized linear regression models: one unweighted model and two weighted by inverse probability of censoring to address potential bias from differences in breastfeeding duration. Models were adjusted for birth weight, infant sex, maternal secretor status, maternal age, maternal education, and household poverty. Growth associations differed by specific HMOs. 3′-sialyllactose (3′SL; β = 0.11, 95% CI: 0.02, 0.21) and difucosyllactose (DFLac; β = 0.04, 95% CI: 0.00, 0.09) were positively associated with LAZ, suggesting a role in promoting linear growth. In contrast, fucosyllacto-N-hexaose (FLNH; β = −0.07, 95% CI: −0.11, −0.01) was negatively associated with WAZ, and disialyllacto-N-hexaose (DSLNH; β = −0.13, 95% CI: −0.21, −0.05) was negatively associated with WLZ, indicating a more complex relationship with weight gain. These associations remained consistent after IPCW adjustment. Distinct HMOs were differentially associated with child growth patterns. The positive associations of 3′SL and DFLac with LAZ and the negative associations of FLNH and DSLNH with WAZ and WLZ underscore the complexity of HMO–growth relationships and highlight the need for future studies to determine whether targeted HMO modulation or supplementation could optimize early growth outcomes.