Nourishing the preterm brain: Optimizing nutrition to support neurodevelopment after preterm birth

Preterm born infants are at risk for brain injury and impaired neurodevelopmental outcomes. Diffuse white matter injury is the most common form of brain injury for which no treatment options exist to date. Human milk contains many components that play an important role in brain development. This thesis aimed to further explore optimization of nutrition as a way to support brain development and neurodevelopmental outcome after preterm birth.

Part I – Non-interventional studies
Based on a retrospective cohort study, increased postnatal protein intake seems important for early white matter development, although its effects on long-term neurodevelopment remains uncertain (Chapter 2). As concluded by a scoping review, optimizing postnatal nutrition can positively influence white matter development and possibly subsequent neurodevelopment. However, more controlled intervention studies using quantitative neuroimaging are needed to determine optimal intakes (Chapter 3).

Part II – The NutriBrain trial
Results of the NutriBrain trial showthat early nutritional supplementation with probiotics (B. breve M-16V), prebiotics (sc-GOS/lc-FOS), and L-glutamine might support development of the right corticospinal tract up to TEA (Chapter 4) and reduce the risk of neurodevelopmental impairment at two years CA after very and extremely preterm birth (Chapter 5). These effects may be mediated by enhancing a Bifidobacterium-dominated gut community during the first weeks of life (Chapter 6).

Part III – The Dolphin CONTINUE trial
The Dolphin CONTINUE trial was designed to test the effect of long-term enteral supplementation with neuronal membrane precursors, including DHA, UMP, and choline, on white matter development and subsequent neurodevelopmental outcome (Chapter 7). The primary results of this trial show that the nutritional intervention can support white matter development during the first months of life (Chapter 8).

Discussion
Despite the various strengths of these studies, many questions remain unanswered, and further research is valuable and necessary. In brief, the recommendations for future research are:
• Take into account other factors that influence brain development, such as the clinical course of the child and the exact composition of the milk feeding.
• Improve the generalizability of the study results by testing nutritional interventions in larger groups of children with more diverse socioeconomic backgrounds and clinical courses.
• Use outcome measures that are sensitive enough to detect an intervention effect, such as combining new MRI techniques with developmental assessments at school age.

In addition, it is important to collaborate across different areas of expertise to further improve nutritional care and to implement new supplements in clinical practice.

Conclusion
Breastfeeding remains the golden standard of nutrition for every neonate, but additional supplementation with key components present in human milk can further support brain development after preterm birth. Future research should continue to optimize nutritional strategies, ultimately improving neurodevelopmental outcomes and the quality of life for these vulnerable infants.