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

Abstract

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 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. Thus, among the macronutrients, greater protein intake contributed 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.

Social-Cognitive Network Connectivity in Preterm Children and Relations With Early Nutrition and Developmental Outcomes

“…Our study extends these findings by showing, in whole-brain MEG analyses, that higher protein and energy intake during the first month of life were associated with increased connectivity in the alpha-frequency band, whereas higher lipid intake was associated with decreased beta-band connectivity. Importantly, the present results complement our previous structural connectivity findings that showed higher intakes of protein and energy during the same postnatal period (days 9–29) were associated with improved white matter microstructure at 5 years of age ( Sato et al, 2021a ). These findings suggest that early macronutrient and energy intakes contribute to the maturation of both functional and structural connectivity in the preterm brain.…”

“…Significant results were also found in the alpha-frequency band, suggesting shared mechanisms by which protein and energy impact resting-state networks underlying cognitive and socio-cognitive functions. This is further supported by our previous diffusion MRI study that found significant associations between protein and energy intake with DTI metrics within many overlapping white matter tracts ( Sato et al, 2021a ). Early protein intake is essential for synaptogenesis and myelination, which undergoes critical development during the preterm period ( Georgieff, 2007 ; Cormack et al, 2019 ).…”

“…Emerging evidence suggests that optimising early postnatal nutrition, particularly macronutrient and energy intake, is associated with improved brain maturation ( Beauport et al, 2017 ; Schneider et al, 2018 ; Blesa et al, 2019 ). Our recent study found that higher protein, lipid, and energy intake during the first postnatal month was associated with improved white matter microstructure in 5-year-old VLBW children from an overlapping sample in the present study ( Sato et al, 2021a ). Consistent with this, Schneider et al (2018) reported that energy and lipid intake during the first 2 weeks of life was significantly associated with increasing fractional anisotropy between birth and term-equivalent age in preterm infants.…”

The impact of breast milk feeding on early brain development in preterm infants in China: An observational study

“…Breast milk contains nutrients that are essential in early infancy, including docosahexaenoic acid (DHA) and long-chain polyunsaturated fatty acids (LC-PUFAs) [ 13 , 14 ]. Emerging studies suggest that breast milk feeding in infancy is associated with improved brain growth, white matter microstructure, and short- and long-term neurodevelopmental performance in preterm infants [ 15 – 18 ].…”

Variation in Neonatal Nutrition Practice and Implications: A Survey of Australia and New Zealand Neonatal Units

“…Much of this research has been underpowered and short-term in design. The interrelationship between nutrition, growth, and neurodevelopmental outcomes reported in these studies can only be interpreted as associative, not causative and results are rarely conclusive (22)(23)(24)(25). There is lack of good quality evidence upon which to base neonatal nutrition practice, leading to clinician opinion or consensus rather than gold standard evidence governing decisions around neonatal nutritional care (26).…”