Effects of nutrition therapy on growth, inflammation and metabolism in immature infants: a study protocol of a double-blind randomized controlled trial (ImNuT)

Abstract

Background Current nutritional management of infants born very preterm results in significant deficiency of the essential fatty acids (FAs) arachidonic acid (ARA) and docosahexaenoic acid (DHA). The impact of this deficit on brain maturation and inflammation mediated neonatal morbidities are unknown. The aim of this study is to determine whether early supply of ARA and DHA improves brain maturation and neonatal outcomes in infants born before 29 weeks of gestation. Methods Infants born at Oslo University Hospital are eligible to participate in this double-blind randomized controlled trial. Study participants are randomized to receive an enteral FA supplement of either 0.4 ml/kg MCT-oil™ (medium chain triglycerides) or 0.4 ml/kg Formulaid™ (100 mg/kg of ARA and 50 mg/kg of DHA). The FA supplement is given from the second day of life to 36 weeks’ postmenstrual age (PMA). The primary outcome is brain maturation assessed by Magnetic Resonance Imaging (MRI) at term equivalent age. Secondary outcomes include quality of growth, incidence of neonatal morbidities, cardiovascular health and neuro-development. Target sample size is 120 infants (60 per group), this will provide 80% power to detect a 0.04 difference in mean diffusivity (MD, mm2/sec) in major white matter tracts on MRI. Discussion Supplementation of ARA and DHA has the potential to improve brain maturation and reduce inflammation related diseases. This study is expected to provide valuable information for future nutritional guidelines for preterm infants. Trial registration Clinicaltrials.gov ID: NCT03555019. Registered 4 October 2018- Retrospectively registered.

Commentary on “Compatibility of rapid enteral feeding advances and noninvasive ventilation in preterm infants – an observational study”

“…(Martin et al 2011) Randomized trials of maternal and preterm infant DHA and arachidonic acid supplementation are ongoing. (Wendel et al 2021) Studies specifically examining the role of PUFAs in reducing risk of lung disease in extremely preterm infants are needed.…”

Commentary on “compatibility of rapid enteral feeding advances and noninvasive ventilation in preterm infants—an observational study”

“…23 Randomized trials of maternal and preterm infant DHA and arachidonic acid supplementation are ongoing. 24 Studies specifically examining the role of PUFAs in reducing risk of lung disease in extremely preterm infants are needed.…”

Oligodendrocyte Development and Implication in Perinatal White Matter Injury

“…Disturbance of cholesterol homeostasis following HI in neonatal brain was associated with worse subcortical white matter development (Kamino et al, 2019;Marangon et al, 2020). To this end, an ongoing clinical trial is currently evaluating the effect of early nutritional supply in brain maturation and neonatal outcomes in preterm infants (ClinicalTrials.gov NCT03555019) (Chan et al, 2016;Wendel et al, 2021). In addition to optimal early nutrition, the impacts of behavioral interventions and environmental enrichment (EE) have been increasingly appreciated in neurodevelopmental outcomes (Bacmeister et al, 2020;Tooley et al, 2021).…”

“…Disturbance of cholesterol homeostasis following HI in neonatal brain was associated with worse subcortical white matter development ( Kamino et al, 2019 ; Marangon et al, 2020 ). To this end, an ongoing clinical trial is currently evaluating the effect of early nutritional supply in brain maturation and neonatal outcomes in preterm infants ( ClinicalTrials.gov NCT03555019) ( Chan et al, 2016 ; Wendel et al, 2021 ).…”