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

Kristina Wendel, Helle Cecilie Viekilde Pfeiffer, Drude Merete Fugelseth, Eirik Nestaas, Magnus Domellöf, Bjorn Steen Skålhegg, Katja Benedikte Presto Elgstøen, Helge Rootwelt, Rolf Dagfinn Pettersen, Are Hugo Pripp, Tom Stiris, Sissel J Moltu, ImNuT Collaboration Group, Marlen Fossan Aas, Mona Kristiansen Beyer, Jens-Petter Berg, Marianne Bratlie, Atle Bjornerud, Maninder Singh Chawla, Siw Helen Westby Eger, Cathrine Nygaard Espeland, Oliver Geier, Gunnthorunn Gunnarsdottir, Christina Henriksen, Per Kristian Hol, Henrik Holmstrøm, Ivan Maximov, Tone Nordvik, Madelaine Eloranta Rossholt, Helene Caroline Dale Osterholt, Ingjerd Saeves, Elin Blakstad, Henriette Astrup, Helge Froisland, Lars Tveiten, Krzysztof Hochnowski, Terje Reidar Selberg, Henning Hoyte, Randi Borghild Stornes, Hanne Isdal, Thea Wauters Thyness, Petra Huppi, Alexandre Lapillonne, Kristina Wendel, Helle Cecilie Viekilde Pfeiffer, Drude Merete Fugelseth, Eirik Nestaas, Magnus Domellöf, Bjorn Steen Skålhegg, Katja Benedikte Presto Elgstøen, Helge Rootwelt, Rolf Dagfinn Pettersen, Are Hugo Pripp, Tom Stiris, Sissel J Moltu, ImNuT Collaboration Group, Marlen Fossan Aas, Mona Kristiansen Beyer, Jens-Petter Berg, Marianne Bratlie, Atle Bjornerud, Maninder Singh Chawla, Siw Helen Westby Eger, Cathrine Nygaard Espeland, Oliver Geier, Gunnthorunn Gunnarsdottir, Christina Henriksen, Per Kristian Hol, Henrik Holmstrøm, Ivan Maximov, Tone Nordvik, Madelaine Eloranta Rossholt, Helene Caroline Dale Osterholt, Ingjerd Saeves, Elin Blakstad, Henriette Astrup, Helge Froisland, Lars Tveiten, Krzysztof Hochnowski, Terje Reidar Selberg, Henning Hoyte, Randi Borghild Stornes, Hanne Isdal, Thea Wauters Thyness, Petra Huppi, Alexandre Lapillonne

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.

Keywords: Arachidonic acid; Brain maturation; Docosahexaenoic acid; Inflammation; Nutrition; Preterm.

Conflict of interest statement

The investigational nutrition product, Formulaid™ was donated by DSM Nutritional Products. All authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Nutritional protocol
Fig. 2
Fig. 2
Summary of study assessments and procedures

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