Early nutrition and white matter microstructure in children born very low birth weight

Infants born at very low birth weight (<1500 g) are vulnerable to nutritional deficits during their first postnatal month, which are associated with poor neurodevelopmental outcomes. Despite this knowledge, the impact of early postnatal nutrition on white matter microstructure in children born with very low birth weight has not been investigated. In this prospective cohort study, we employed a whole-brain approach to investigate associations between precise estimates of nutrient intake within the first postnatal month with white matter microstructure at 5 years of age. Detailed information about breastmilk, macronutrient and energy intakes during this period were prospectively recorded for all participants. Multi-shell diffusion and T₁-weighted MRIs were acquired in 41 children (21 males; mean scan age: 5.75 ± 0.22 years; mean birth weight: 1028.6 ± 256.8 g). The diffusion tensor imaging and neurite orientation dispersion and density imaging models were used to obtain maps of fractional anisotropy, radial diffusivity, orientation dispersion and neurite density indices. Tract-based spatial statistics was used to test associations between metrics of white matter microstructure with breastmilk, macronutrient (protein, lipids and carbohydrate) and energy intake. Associations between white matter microstructure and cognitive outcomes were also examined. Compared to children who did not meet enteral feeding recommendations, those who achieved enteral protein, lipid and energy recommendations during the first postnatal month showed improved white matter maturation at 5 years. Among the macronutrients, greater protein intake contributed most to the beneficial effect of nutrition, showing widespread increases in fractional anisotropy and reductions in radial diffusivity. No significant associations were found between white matter metrics with breastmilk or carbohydrate intake. Voxel-wise analyses with cognitive outcomes revealed significant associations between higher fractional anisotropy and neurite density index with higher processing speed scores. Lower radial diffusivity and orientation dispersion index were also associated with improved processing speed. Our findings support the long-term impacts of early nutrition on white matter microstructure, which in turn is related to cognitive outcomes. These results provide strong support for early postnatal nutritional intervention as a promising strategy to improve long-term cognitive outcomes of infants born at very low birth weight.