Abstract
Background: Preventing neurodevelopmental impairment after extremely preterm birth remains challenging. While breast milk feeding is linked to better neurodevelopment, the underlying mechanisms are unclear. This study explored the association between individual human milk oligosaccharides (HMO) and neurodevelopment at two years of age in extremely preterm children. Methods: Milk samples from mothers of 76 extremely preterm infants collected at two weeks after birth were analyzed for 15 dominant HMOs. Register data from examination and Bayley-III neurodevelopmental assessment at two years' corrected age was retrieved and categorized into levels of impairment. An exploratory analysis examined associations between the HMO composition and neurodevelopment. Results: Bioinformatic volcano plots revealed associations between specific HMOs and outcomes: 3FL with less neurodevelopmental impairment, LSTb with higher Bayley-III cognitive scores, and LSTa with worse neurodevelopmental impairment outcomes. Spearman correlations indicated LSTa was linked to more neurodevelopmental impairment (p = 0.018), lower language (p = 0.009), and motor (p = 0.02) scores, whereas 3FL correlated with less neurodevelopmental impairment (p = 0.02). Dichotomized analysis showed LSTa was associated with more neurodevelopmental impairment and lower language scores (p < 0.05), 3FL with milder neurodevelopmental impairment (p < 0.05), and LSTb with better cognitive (p < 0.01) and language (p < 0.05) scores. No significant associations were found for HMO diversity, total sialic acid content, or secretor/Lewis patterns. Conclusions: In this explorative hypothesis-generating study, certain HMOs appeared to be associated with both potentially beneficial and adverse neurodevelopmental outcomes in extremely preterm infants. However, these findings should be interpreted with caution, as they do not constitute evidence but rather serve as a preliminary foundation for future hypothesis-driven research.