Essential Fatty Acid Deficiency, Immature Infant
Conditions
Keywords
Brain maturation, Postnatal growth
Brief summary
The primary objective of this double-blind randomized study is to assess the effects of an early, enhanced supply of the essential fatty acids (FAs) arachidonic acid (ARA) and docosahexaenoic acid (DHA) on brain maturation, clinical outcomes and quality of growth in immature infants (gestational age \<29 weeks) as compared to standard nutrient supply.
Detailed description
This is a double-blind randomized study. 172 preterm infants with gestational age \< 29 weeks will be enrolled. The intervention group will receive enteral supplementation with essential fatty acids, arachidonic acid (ARA) and docosahexaenoic acid (DHA). The control group will receive standard supplementation with medium-chain triglycerides (MCT-oil). The main hypothesis is that early, enhanced supply of ARA and DHA will improve brain growth and maturation, as compared to standard nutrient supply. Secondary hypotheses are that early, enhanced supply of ARA and DHA will improve quality of growth and cognitive development as well as reduce the frequency of inflammation-related neonatal comorbidities and long-term cardiovascular disease risk. Primary endpoint will be assessed by magnetic resonance imaging (MRI) of the brain at term equivalent age.
Interventions
DIETARY_SUPPLEMENTFormulaid
Supplementation with ARA and DHA
DIETARY_SUPPLEMENTMCT-oil
Supplementation with medium chain fatty acids
Sponsors
University of Oslo
Umeå University
University of Geneva, Switzerland
Oslo University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Double-blind, randomized-controlled. Parallel group, single center trial
Eligibility
Sex/Gender
ALL
Age
No minimum to 48 Hours
Healthy volunteers
No
Inclusion criteria
* Extremely preterm infants born at Oslo University Hospital (OUH) * Gestational age (GA) \< 29 weeks * Less than 48 hours of age at inclusion * Signed informed consent and expected Cooperation of the patients for the treatment and follow up must be obtained and documented according to good clinical practice (GCP) and national/local regulations
Exclusion criteria
* Major congenital malformations which will affect growth and development * Chromosomal abnormalities and other genetic diseases * Critical illness with short life expectancy as defined by the study physician
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brain maturation assessed by magnetic resonance imaging (MRI) | 40 weeks postmenstrual age (PMA) | MRI with spectroscopy (MRS) and diffusion tensor imaging (DTI) will be used to examine myelinisation and quantification of anatomical structures as well as neuronal integrity and inflammation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Growth | Length and HC will be recorded until 36 weeks PMA and at 3, 6, 12 and 24 months and 8 years corrected age. | Length and head circumference (HC). |
| Body composition | At 36 weeks PMA, 3 months and 2 years corrected age | Body composition will be assessed using PEA POD, an air displacement plethysmography system and Dexa Scan. |
| Neonatal morbidities associated with inflammation | From birth til 36 weeks PMA | Bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), white matter injury (WMI) of the brain, and late onset septicemia |
| Cerebral Background Activity evaluated by Electroencephalogram (EEG) | First week of life, 36 weeks PMA and 2 years corrected age (CA) | EEG maturational changes will be examined as a function of time and as a function of gestational age |
| Neurodevelopment assessed by standardized motor and cognitive tests | 2 years corrected age (CA) | Evaluation of psychomotor development by performing Bayley III and a standardized neurological examination |
| Lung function evaluated by tidal breathing measurements | 36 weeks PMA, 3 months and 2 years CA | Tidal breathing measurements include tidal volume, respiratory rate, minute ventilation and fraction of expiratory time to peak tidal expiratory flow to total expiratory time |
| Cardiovascular Health assessed by echocardiography | First week of life, 2nd week of life, at 36 weeks PMA and 2 years CA | Echocardiography will be used to follow the transition from fetal to completed neonatal circulation, to measure superior vena cava flow, and to study mycardial function by the use of conventional two-dimensional echocardiography and tissue Doppler imaging. |
| Blood pressure | First week of life and at 36 weeks PMA and 2 years CA | Measurements of systolic, diastolic and mean pressure |
| Weight gain | Weight will be recorded until 36 weeks PMA and at 3, 6, 12 and 24 months and 8 years corrected age. | Weight measurements, including weight nadir. |
| Markers of inflammation | From birth until 36 weeks PMA | Inflammation panels will be used to assess markers of inflammation in fullblood and sputum |
| Markers of metabolic status | From birth until 36 weeks PMA | Metabolic pathway analyses (http://omictools.com/metabolic-pathways-category) will be performed to analyse and describe the metabolic conditions of the infants during hospitalization. Metabolites outside the standard clinical chemistry parameters will also be investigated (untargeted metabolomics). Metabolomics will be performed by the use of dried blood spot samples |
| Markers of nutritional status in blood | From birth until 36 weeks PMA | The concentrations of electrolytes, minerals, albumin, alkaline phosphatase, vitamin A and D will be assessed regularly during hospitalization |
| Micronutrient content in urine | From birth until 36 weeks PMA | Spot urine will be obtained regularly to study the changes in electrolyte- and mineral homeostasis during the first week of life as well as during the phase of steady growth |
| Evaluation of nutrient composition of expressed breast milk | From birth until 36 weeks PMA | Repeated samples of breast milk will be collected for FA analyses, macronutrient content and vitamin A |
| Gut microbiota | From birth until 36 weeks PMA | Repeated samples of feces will be used to study the early fecal microbiota |
| Inflammatory markers in sputum | From birth until 36 weeks PMA | We will analyze the Expression of a standardized panel of inflammatory markers in collected laryngeal or tracheal secretion |
| Fatty acid (FA) profiles in blood | From birth until 36 weeks PMA | Repeated dried blood spots (DBS) samples with approximately 10 µL blood will be collected for FA analyses. These analyses are important for assessing efficacy and protocol compliance. We will also collect 10 µL of fullblood for assessment of total lipid profile (Lipidomics). |
Countries
Norway
Outcome results
None listed