Investigating the clinical and cost-effectiveness of a nutrient enriched diet for babies with a brain injury: The DOLFIN Randomised controlled trial

Research question

In babies born very pre-term or with less oxygen around the time of birth (participants), does nutritional fortification with DHA, choline and uridine-5-monophosphate (intervention) plus usual care from birth to 12 months of age corrected for prematurity improve cognitive development (outcome) at 2-years of age corrected for prematurity, compared to babies receiving a matched control fortifier plus usual care (comparator)?

Background

Babies born pre-term or with less oxygen around the time of birth are at risk of neurodisability, and suboptimal long term neurodevelopmental outcomes and educational attainments. Adequate provision of key brain nutrients may support brain plasticity and development following perinatal brain injury, and improve neurodevelopmental outcomes

Aims and objectives

1 Investigate, in a multicentre randomised placebo-controlled trial, the effect of nutritional fortification with DHA, choline and UMP on neurodevelopmental outcomes at 2-years corrected gestational age 2 Assess the safety of fortification

3 Conduct an internal pilot study to evaluate: recruitment, parental uptake and retention rates; clinician protocol adherence; safety; parent acceptability and adherence; completeness and quality of data collection

4 Determine the intervention’s impact on healthcare service use, parental health-related quality of life, parent employment, and value for money (NHS and society) using an economic evaluation

5 Facilitate a follow up study into the intervention’s effect on later developmental, health, healthcare resource use, and educational outcomes using routinely collected data Methods

Multicentre blinded randomised placebo-controlled trial with an internal pilot and economic evaluation. Babies recruited from NHS Tertiary neonatal units will include: 1010 preterm babies born less than 28 weeks of gestation, and babies born at 35 weeks gestation or more receiving therapeutic hypothermia for HIE

Intervention: Micronutrient breast milk/formula milk/food fortifier containing DHA, choline and UMP for newborns born pre-term or who receive less oxygen around the time of birth. Comparator: Matched control fortifier: identically packaged and delivered powder fortifier indistinguishable from the active treatment. Both groups will receive identical usual care (NHS breastfeeding, dietetic and other multidisciplinary team support) and clinical research team support

Primary outcome (age 24 months, corrected for prematurity): PARCA-R Non-verbal Cognitive Scale score. Secondary outcomes: PARCA-R Language Development Scale score; motor, behavioural, attention, social and emotional outcomes. NHS data at 1 and 2-years for Safety, Health (necrotising enterocolitis, sepsis, chronic lung disease); Growth (height, weight, obesity, head circumference); need for social care. Parent acceptability of intervention and adherence. Economic evaluation

Timeline Start 1.9.2021 0-6 mths Permissions, site set-up, create breastfeeding support and other materials in partnership with parents 7-33 mths Recruitment, internal pilot, community fortification 7-63 mths Community fortification, outcome measurement 64-69 mths Analysis, dissemination Impact and dissemination

The pilot Dolphin neonatal trial showed a non-significant difference in neurodevelopmental outcomes between fortifier and control groups. This definitive trial will give clarity to parents and professionals on whether nutritional intervention improves outcomes, or not. If fortifier is effective, this may alter neonatal care pathways. We will disseminate to: professionals; parents, the public; and policymakers