Title: 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)
Funder: Department of Health and Social Care

Abstract: In the UK around 8% of babies born are premature at birth and around 12% of these babies are born between 30 and 33 weeks and 0 days of gestation. Currently, most preterm babies are fed through a drip into their veins (intravenous) and to start with are given only small amounts of milk by a small tube into their stomach. The milk is slowly increased until they are fully milk fed. Doctors are wary of feeding premature babies with full milk straight after birth due to a potentially life-threatening gut condition called necrotising enterocolitis (NEC). Evidence suggests that in premature babies who aren’t too poorly, larger milk feeds can be successfully given within 48 hours of birth without increasing the risk of NEC and death, and could reduce the risk of severe infection. _x000D_ _x000D_ Reducing the time to when the baby is fully milk fed may have other benefits: making care more normal, allowing parents to feed, spend more time, and bond with their babies, and give the baby the benefits of breast milk earlier. This could mean the baby may be ready to go home sooner and the length of an expensive hospital stay may be reduced bringing families together sooner. This could reduce the demand for scarce neonatal cots, for which sick babies are often transported long distances as, often, there are not enough cots and staff in the hospital in which they were born. _x000D_ _x000D_ The FEED1 study will investigate the best way to feed babies born between 30 and 33 weeks gestation. We want to know if babies born at these gestation weeks can be safely fully milk fed from the first day of life and if avoiding giving them fluids through a drip (IV) can reduce infections and help them go home sooner. As such babies cannot feed directly from the breast, we aim to support mothers to start expressing breast milk as soon after birth as possible. We will give this milk first to the baby and then give extra milk, if needed. The type of milk the baby receives will be decided by the mother’s choice with staff guidance but any mother's breast milk will always be given first. _x000D_ _x000D_ We will compare two different groups: the ‘full milk’ group will be given milk to provide all their fluid needs from the first day of life. The amount of milk given will be increased over a few days and the babies in this group will get all their fluids as milk unless they are struggling with this, e.g. if it makes them very sick. In the “gradual milk” group, babies will be initially fed through their veins, and milk feeds will be given in smaller amounts and increased slowly. This is the way in which these babies are currently fed across the UK. The groups will be decided at random by a computer. Each baby will have an equal chance of being in either group. _x000D_ _x000D_ We want to know if feeding babies in this way could reduce the length of time babies stay in hospital. We know this is important from talking to parents of premature babies who have told us that going home even a few days early would make a big difference to their wellbeing. We are also interested in the risk of infection, NEC, parent’s feelings about how their baby is fed, and breast feeding rates. We shall follow-up the babies at two times points, via a parent completed questionnaire (online or paper). At 6-weeks (corrected for prematurity) we shall collect information on the baby’s feeding regime and visits to hospital since being discharged, as well as assessing parental satisfaction. At 2-years of age (corrected for prematurity) we shall collect information on neurodevelopmental outcomes as well as health care visits.

Lay abstract: 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._x000D_ _x000D_ 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. _x000D_ _x000D_ 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. _x000D_ _x000D_ 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. _x000D_ _x000D_ 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. _x000D_ _x000D_ 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. _x000D_ _x000D_ 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.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH