NutriBrain: A controlled study to investigate the effect of a food product on brain development in very early born infants

INTERVENTION: Infants are randomised to be treated with either: 1. Intervention group: a mixture of probiotics, prebiotics and free amino acid 2. Control group: maltodextrin, casein and whey protein hydrolysates Treatment will be provided from 48‐72 hours after birth until 36 weeks postmenstrual age (meaning 36 weeks of the expected pregnancy duration). If the infant is transferred to a regional hospital the treatment will continue at that hospital. Thereafter, the infants will be followed until 2 years corrected age. During the treatment period feeding details (intake and tolerance) will be collected. In addition, a number of samples will be collected. These samples include stool samples, samples of skin cells; samples of mucus membrane from the nose and mouth and in total 6 blood samples of 0.5 to 1 ml. The blood samples will only be collected during regular blood samples, which are being taken as part of standard care. At the expected date of delivery, and in some cases also at 30 weeks of the expected pregnancy duration, a scan of the brain (MRI scan) will be performed to measure growth, development and possible injury of the brain. During the first 2 years of the infants, additional samples of skin cell, mucus membrane and stool will be collected. This will be done during regular hospital visits (no additional visits for the study will be required). At the visit at 2 years of age the blood pressure of the infant will be assessed once. CONDITION: Extremely and very preterm infants ; Neonatal Diseases PRIMARY OUTCOME: Fractional anisotropy in the posterior limb of the internal capsule, assessed on diffusion tensor imaging‐MRI at Term Equivalent Age (TEA) SECONDARY OUTCOME: 1. White matter injury score, assessed according to Woodward et al. and Kidokoro et al. on T2 and T1 weighted MR images measured at TEA ; 2. Brain tissue volumes (cerebellar, cortical grey matter, unmyelinated white matter, deep nuclear grey matter and ventricular volumes, and cerebrospinal fluid) and cortical morphology (sulcation index and cortical thickness), assessed on T2 and T1 weighted MR images measured at TEA ; 3. Cognitive, fine and gross motor development, assessed using Bayley Scales of Infant and Toddler Development‐Third Edition at 24 months corrected age ; 4. Occurrence of serious neonatal infections (defined as culture proven infection with clinical symptoms of an infection; clinically significant necrotising enterocolitis (defined as Bell’s stage two or higher); and/or meningitis with or without positive culture; or clinical respiratory infection = 4 white blood cells per field associated with a specific pathogen in the tracheal aspirates; according to the categories proposed by Stoll et al.) until TEA; 5. Serum concentrations of specific circulating inflammatory markers such as IL‐6, IL‐10, TNF‐a and IL‐8/CXCL8, measured at fixed time points INCLUSION CRITERIA: 1. Gestational age of 24+0 to <30+0 weeks (by the best estimate of expected date of delivery) 2. Less than 72 hours old, and the possibility to receive the first administration of study product between 48‐72 hours after birth 3. Written informed consent from custodial parent(s)