Fluids Exclusively Enteral from Day 1 (FEED1): A randomised controlled trial of full milk feeds versus intravenous nutrition with gradual feeding for preterm infants (30-33 weeks gestational age)

The optimal way to feed preterm infants is a research priority. Around 12% of preterm infants are born between 30-33 weeks gestation forming 42% of routine admissions to neonatal units. Most are started on intravenous (IV) fluids and milk feeds are slowly introduced via gastric feeding tube. Clinicians are wary of milk feeding due to a potentially life-threatening condition called necrotising enterocolitis (NEC). Evidence suggests that feeding preterm infants earlier and faster does not increase NEC and could reduce the risk of infection and death. Full milk feeding and avoiding of IV fluids may have other benefits: less pain from interventions like IV drips, reduced medicalisation of care, greater parental involvement, and parent-infant bonding. These could improve weight gain, encourage establishment of oral feeding, and facilitate earlier discharge. Improved nutrition and mother’s milk during this nutrition sensitive period of brain development, could also enhance neurodevelopment and lifelong quality of life. UK Neonatal units are under constant pressure for cot space: nearly 1,000 infants are transferred each year due to insufficient staffing and resources. Such transfers are risky and separate families. Reducing hospital stays by 2 days for 30-33 week infants would create around 12,600 days of cot capacity and save over £5.5m. These savings would be in addition to lower costs due to reduced use of IV lines, parenteral nutrition, and fewer cases of infections. We propose a multi-centre, open, parallel, randomised controlled, superiority trial to investigate the hypothesis that in infants born at 30-33 weeks gestational age, starting full milk feeds from day 1 when compared to current practice of parenteral nutrition/IV fluids with gradual milk feeding will reduce length of hospital stay by 2 days. Secondary outcomes include NEC, sepsis, growth, breast feeding, use of parenteral nutrition, and parental wellbeing. A full economic analysis will be performed. This study has been developed in collaboration with parents of preterm infants and Bliss who will lead on involving families at all stages. Consent will be before or after birth and the unit of randomisation will be the mother. After birth the infant’s eligibility for the trial will be checked and the mother randomised to a “full milk” or a “gradual milk” group. Infants in the “full milk” group will be started on full milk feeds via gastric tube while those in the “gradual milk” group will be treated as per standard practice. All mothers will be supported to express breast milk, which will be the first choice milk. If there is insufficient mother’s milk, donor breast milk or formula milk will be used. We will collect data on daily feed and fluid logs until full feeds (150ml/kg/day for 3 days) is reached. Outcome at hospital discharge will be collected via electronic and paper forms. At 6 weeks of age (corrected for prematurity), readmission rates, breast feeding rates, and parental satisfaction will be collected via a parent completed questionnaire (paper or online). At 2-years of age (corrected for prematurity) neurodevelopmental outcomes will be collected via a parent completed (paper or online) questionnaire. In keeping with the NHS "Five Year Forward View" aim of achieving efficiency savings while maintaining and improving quality of care and safety, we believe that full milk feeds from birth may be an intervention that improves outcomes and care of preterm infants and their families while simultaneously reducing the cost of care.