INVESTIGATING THE IMPACT OF HUMAN MILK OLIGOSACCHARIDES ON CHILD DEVELOPMENT

Investigating the impact of Human Milk Oligosaccharides on child development in León, Nicaragua. Human milk oligosaccharides (HMOs) are bioactive components of breast milk with growing evidence suggesting roles in shaping infant growth and neurodevelopment. However, their long-term effects remain poorly understood, particularly in underrepresented populations.This dissertation examined the associations between individual HMO concentrations measured at one month postpartum (or the closest timepoint for which we had a sample) and two developmental outcomes in a population-based birth cohort from León, Nicaragua: linear growth at 24 months and neurodevelopment at around 48 months of age. Linear growth was assessed using the World Health Organization standardized z-scores for length-for-age (LAZ), weight-for-age (WAZ), and weight-for-length (WLZ). Neurodevelopment was evaluated using the Mullen Scales of Early Learning (MSEL), including subdomain and composite scores. Human milk samples were analyzed using high-performance liquid chromatography with fluorescence detection (HPLC-FL). Associations were estimated using generalized linear regression models, both unweighted and weighted using inverse probability of censoring weights (IPCW) to account for variation in breastfeeding duration. Models adjusted for maternal, infant, and household-level covariates.In Aim 1, higher concentrations of sialylated HMOs, including 3′-sialyllactose (3′SL), difucosyllactose (DFLac), sialyllacto-N-tetraose c (LSTc), and disialyllacto-N-tetraose (DSLNT), were positively associated with LAZ, suggesting a potential role in promoting linear growth. Notably, 3′SL and DFLac showed consistent associations across both multivariable and IPCW-weighted models. In contrast, higher concentrations of fucosyllacto-N-hexaose (FLNH) and disialyllacto-N-hexaose (DSLNH) were negatively associated with WAZ, indicating potential inverse relationships with weight-related growth indicators.In Aim 2, higher concentrations of sialylated HMOs, particularly 3′SL and LSTc, were negatively associated with multiple MSEL domains, including visual reception (VR), fine motor (FM), expressive language (EL), and the Early Learning Composite (ELC). Additionally, non-fucosylated lacto-N-hexaose (LNH) and fucosylated FLNH demonstrated inverse associations with several MSEL domains. These associations remained robust in sensitivity analyses restricted to secretor mothers and after applying IPCW.These findings highlight the complex, domain-specific associations between early-life HMO exposures and child growth and neurodevelopment. They underscore the importance of investigating HMO profiles in diverse populations to inform future personalized nutrition strategies, particularly in low- and middle-income settings.