Effects of nutrition therapy on growth, metabolism and inflammation in immature infants; a double-blind randomized, controlled trial

INTERVENTION: Trade Name: Clinoleic Pharmaceutical Form: Emulsion for infusion Trade Name: Omegaven Pharmaceutical Form: Emulsion for infusion CONDITION: Therapeutic area: Diseases [C] ‐ Nutritional and Metabolic Diseases [C18] To determine whether early and prolonged supply of ARA and DHA improves quality of growth and clinical outcomes in extreme premature infants as compared to our present nutrient supply. By closely assessing nutritional intake, anthropometric measures, clinical outcomes and several biomarkers of inflammation and metabolism, we hope to elucidate mechanisms of inflammation and metabolic mediated damage to major organs such as brain, lung, eye and cardiovascular system of extremely premature infants. PRIMARY OUTCOME: Main Objective: To assess the effects of an early nutritional intervention on clinical outcomes and quality of growth in extreme premature infants (gestational age < 29 weeks). ; Main hypothesis: Early, enhanced supply of the essential FAs DHA and ARA will improve brain growth and maturation, as compared to standard nutrient supply.; Primary end point(s): Brain maturation assessed by MRI with spectroscopy (MRS) and diffusion tensor imaging (DTI) Secondary Objective: To explore potential differences in inflammatory and metabolic pathway responses related to nutrient supply, age, sex, comorbidities, as well as pre‐ and postnatal growth. ; ; Secondary hypotheses: Early, enhanced supply of the essential FAs DHA and ARA will improve quality of growth and cognitive development and it will reduce the frequency of inflammation‐related neonatal comorbidities and long‐term cardiovascular disease risk. ; Timepoint(s) of evaluation of this end point: Term equivalent age (+/‐ 2 weeks). SECONDARY OUTCOME: Secondary end point(s): 1) Nutritional intakes ; 2) Anthropometric measurements: Weight nadir, time to regain birth weight, change in weight, length and HC (absolute and z‐scores), and growth velocity from birth to 28 days and 36 weeks postmenstrual age (PMA), and at 3, 6, 12 and 24 months as well as 8 years CA. ; 3) Body composition ; 4) The cumulative incidence of neonatal morbidities associated with inflammation (BPD, ROP, NEC, WMI, and late onset septicemia). The frequency of persistent ductus arteriosus, postnatal growth restriction, hyperglycemia and hypotension. ; 5) Inflammatory, metabolic and nutrient markers in blood, urine and feces. ; 6) Neurodevelopment assessed by neurological and neuropsychological examinations as well as sophisticated neuroimaging modalities and neurophysiological tests. ; 7) Cardiovascular health assessed by echocardiography (both structural and functional) and with blood pressure (BP) measurements. ; 8) Lung function Timepoint(s) of evaluation of this end point: 1) daily during neonatal hospitalization ; 2) during neonatal hospitalization: weight daily, HC/lenght weekly; thereafter as given above. ; 3) at 36 weeks PMA, 6 months, and 8 years CA ; 4) short‐time clinical outcomes will be registrered during neonatal hospitalization ; 5) days 0,1,2,3,5,7,14,21,28, and at 32 and 36 weeks PMA as well as at 3, 6, 12, and 2 and 8 years CA. ; 6) cerebral ultrasound and EEG at days 0,1,2 and at 32 and 36 weeks PMA. EEG also at 24 months CA. Standardized neurological examination and neuropsychological test (Bayley III) at 2 years CA. MRI at 8 years CA. ; 7) Echocardiography at days 0,1,2 and at 36 weeks PMA as well as at 2 and 8 years CA ; 8) Lung function at 36 weeks PMA and at 2 and 8 years CA INCLUSION CRITERIA: All extremely preterm infants born at OUH between 01.09.17 and 31.12.19 with GA<29 weeks are eligible. Oral consent to participate is needed before inclusion. As soon as possible, and at latest within 24 hours of life, the caregivers will be introduced to all study details and the ICF has to be signed before further participation. Are the trial subjects under 18? yes Number of subjects for this age range: 120 F.1.2 Adults (18‐64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range