A new very large (for neonatology) RCT has just been published. Ojha S, et al. Full exclusively enteral fluids from day 1 versus gradual feeding in preterm infants (FEED1): a open-label, parallel-group, multicentre, randomised, superiority trial. Lancet Child Adolesc Health. 2025. Mothers were approached prior to preterm delivery, and babies were enrolled if they delivered between 30 and >33 weeks gestation, and were deemed clinically stable, prior to 3 hours of age. Prior to delivery the mothers either gave full written signed consent, or they verbally agreed to the study, in which case they had a full written consent later. This allowed babies to be enrolled early in life, at an average of about 1.5 hours. Twins were therefore randomized as a unit to the same group, there were 2088 babies from 1761 mothers.

About half of the babies already had an IV when they were enrolled. In the intervention group, babies then received “full-milk-feeds”, starting at 60-80 mL/kg/d (the published protocol states 60 mL/kg/d), whereas the control group had a maximum of 30 mL/kg/d enteral liquids on day 1.

This is described thus : “For infants in the full milk group, we started milk feeds within 3 h of birth at 60–80 mL/kg per day via a gastric tube and continued milk feeds without intravenous fluids or parenteral nutrition”. But this just isn’t true, 80% of the full milk group infants did have intravenous fluids on day 1, as their own figure shows. I think this is really just a question of wording, the full milk group babies were supposed to attempt full enteral nutrition, but large numbers of babies in this GA group will have expectant IV antibiotics for possible early onset sepsis, so they required IV access for good clinical care. 50% of the babies had an IV at enrolment (there is no mention anywhere in the publication or the supplementary materials of IV antibiotics). This also means that 300 babies in the full feeds group had an IV inserted, within the first few hours of birth, after they were assigned to the full enteral feeding group. This is never explained, or even mentioned or discussed.

They also never state what was done with feeding volumes for infants who had an IV running; were the IV fluids included in the fluid calculation? If a baby weighed 1.2 kg, for example, and had an IV running at 2 mL/h for their antibiotics, was the 40 mL/kg/d of IV liquid in addition to the enteral liquids? Or was that volume deducted from their feeds? This is an important detail given that 80% of the “full enteral” group had IV fluids.

After the initiation of the trial, the local care team could do whatever they wanted, in terms of increasing feed rate, or the source of additional feeds (donor milk or formula), or defining feed intolerance, or measuring gastric residuals(!), or timing of fortification. Full feeds were defined as at least 140 mL/kg/d for 3 consecutive days.

Forty percent of the “full enteral feeding” group had more than 24 hours of IV fluids, but again we have no idea how much of this was due to IV antibiotic use. The babies were all preterm, many had respiratory distress, more than a fifth had ruptured membranes for >24 hours, so I am sure that many had (and needed) IV antibiotics. On the other hand, there were 71% who were delivered by Cesarean section, and babies delivered by CS with intact membranes don’t need antibiotics.

I am sure some also needed IV dextrose for treating hypoglycaemia; we are told that the incidence of hypoglycaemia was the same between groups, but how many had an IV for low blood sugar on day 1 is not reported. In the supplemental data we learn that there were about 7% of babies in the full feeds group who “did not adhere to the protocol”, i.e. had intravenous fluids after 24 hours of age, who were in that situation because of hypoglycaemia. Also, 4% of the full feeds group had an IV after 24 hours of age for “other clinical reasons”, which I guess must include IV antibiotics, but that seems extremely low to me. 12% if them had an IV for not tolerating full feeds, and, as mentioned, 7% for hypoglycemia, In other words, nearly 90% of the babies did tolerate full feeds from birth.

The primary outcome was duration of hospitalisation, which was determined according to local practice. There was no impact of study group on the primary, just over 32 days in each group. There were also no differences in the secondary outcomes of NEC (which was rare, 4 cases vs 6 cases), or late-onset sepsis (which was uncommon, 3% vs 2%). Among gestational age subgroups, the primary and these secondary outcomes were similar.

There were differences in TPN use, number and duration of central line use, and the numbers of peripheral IVs inserted, as you would guess, these were all reduced in the early enteral feeds group.

My take away from this trial, and several other smaller trials, is that full nutritional support can be given, from birth, by the enteral route in a large proportion of preterm infants of 30 to 34 weeks, and if they have no other clinical indication for an IV access, one can completely avoid IVs. Infants who need IV antibiotics can usually have their antibiotics discontinued at 36 hours of age (because most of them have negative cultures), after which most of them can be on full enteral fluids. A number of recent trials, some of which I have discussed in the blog have shown the toxicity of TPN. These new data show that a large proportion of the 30 to 34 weeks babies (the majority of preterm babies in the NICU) can be managed without ever receiving TPN. They can also avoid the pain of IV insertion attempts, and the discomfort of IV infiltration episodes.

There does not seem to be any good reason to start at less than 60 mL/kg/d of enteral milk feeds in this group of babies on day 1. Some babies will have difficulty tolerating this, especially infants with IUGR, and in those babies you may need to slow down feeding advancement, or even sometimes to back down to smaller volumes or temporarily stop feeds. Some will also need IV glucose, but I can’t see any good reason for not at least trying to give full enteral nutrition from birth in these babies, even if they need IV access, and a small volume of crystalloid solution, for antibiotic administration.