Nutrition in preterm infants: optimizing brain development and neurodevelopmental outcome

This thesis focuses on the effect of nutrition on brain development and neurodevelopmental outcome in very (gestational age 28-32 weeks) and extremely (gestational age <28 weeks) preterm born infants. These infants are at risk for complications, such as brain injury, neurodevelopmental impairments, and death, due to the immaturity of their organs at birth. Brain injury is quite common in preterm infants. It is commonly referred to as encephalopathy of prematurity, an umbrella term used to indicate several forms of injury, with white matter injury being the predominant form. Feeding preterm infants is a challenge, because their immature gastrointestinal tract can encounter difficulties with processing. Furthermore, preterm infants miss out on the period of nutrient accumulation in the third trimester of pregnancy, which emphasizes the need for adequate feeding after birth. First, we performed a systematic review, in which we included both clinical and preclinical studies, to evaluate the impact of single nutrient interventions on brain development and neurodevelopmental outcome. We found that many nutritional interventions in preclinical models have positive effects on outcome. However, these positive effects cannot easily be translated into clinical practice as we found no long-term positive effects of nutritional interventions in clinical studies. Furthermore, we evaluated several nutritional components in relation to brain development, measured with magnetic resonance imaging at term equivalent age, and/or neurodevelopmental outcome, assessed at 2 years corrected age and 5 years of age. We found that total protein intake in the first 28 postnatal days was positively associated with the development of white matter tracts at term equivalent age. Intake of macronutrients (protein, fat, calories) in the first 28 postnatal days was, however, not associated with neurodevelopmental outcome at school age. In addition, we found that serum blood levels of the fatty acid docosahexaenoic acid and the growth factor insulin-like growth factor-1 in the first 28 postnatal days were positively associated with brain volumes at term equivalent age. Sufficient nutrient intake seems therefore highly important for brain development. Finally, we describe the study protocol of the NutriBrain study, a new randomized, controlled, clinical trial, in which we aim to improve brain development and neurodevelopmental outcome with a nutritional intervention that consists of a combination of probiotics, prebiotics, and glutamine.