Full exclusively enteral fluids from day 1 versus gradual feeding in preterm infants (FEED1): a open-label, parallel-group, multicentre, randomised, superiority trial

<p dir="ltr">Background</p><p dir="ltr">Preterm infants typically receive intravenous fluids or parenteral nutrition while milk feeds are gradually increased. Feeding with milk sooner could reduce length of hospital stay and risk of invasive infections but might increase the risk of necrotising enterocolitis. We aimed to investigate if exclusively enteral fluids (ie, full milk feeds) from day 1 compared with gradual feeding supplemented with intravenous fluids or parenteral nutrition reduces the length of hospital stay in infants born at 30 weeks and 0 days (30+0weeks) to 32+6 weeks of gestation.</p><p dir="ltr">Methods</p><p dir="ltr">This open-label, parallel-group, multicentre, randomised, superiority trial recruited mothers of infants born at 30+0 weeks to 32+6 weeks of gestation, in 46 neonatal units in UK hospitals. Infants younger than 3 h were included if they were clinically stable; those with congenital anomalies that make enteral feeding unsafe and who were small for gestational age with reversed end-diastolic flow on umbilical doppler were excluded. Parents and the clinical team could not be masked, but investigators and data analysts were masked until after database lock. The mother was randomly assigned to either full milk feeds (60–80 mL/kg per day) or gradual milk feeding (maximum of 30 mL/kg per day on day 1) with intravenous fluids or parenteral nutrition for their infant within 3 h of birth using a web-based minimisation algorithm with a random element to ensure balance on important prognostic factors. The primary outcome was length of hospital stay; events of hypoglycaemia and necrotising enterocolitis were safety outcomes and analysis was performed by intention-to-treat. This trial was prospectively registered (ISRCTN89654042) and follow-up to 24 months is ongoing.</p><p dir="ltr">Findings</p><p dir="ltr">Between Oct 15, 2019, and July 14, 2024, we recruited and randomly assigned 1761 mothers, enrolling 2088 infants (1047 full milk feeds, 1041 gradual feeding). Mean gestational age was 31·7 weeks (SD 0·8), which was the same in both groups, and mean birthweight was 1626·0 g (301·8) in the full milk feeds group and 1617·1 (295·2) in the gradual feeding group. Of 1047 infants in the full milk group, 494 (47·2%) were female and 552 (52·7%) were male and in 1041 infants in the gradual feeding group, 500 (48·0%) were female and 540 (51·9%) were male. Primary outcome data were missing for 18 infants in each group. We found no difference in the length of hospital stay (32·4 days [SD 13·3] in the full milk group vs 32·1 days [13·5] in the gradual feeding group; adjusted difference between means –0·02 days [95% CI –1·07 to 1·03]; p=0·97). Survival to discharge (1030 [99·6%] of 1034 vs 1027 [99·6%] of 1031; –0·004 [95% CI –0·54 to 0·53]), presence of necrotising enterocolitis (4 [0·4%] of 1030 vs 6 [0·6%] of 1027; –0·19 [–0·80 to 0·41]), and mean number of blood glucose tests <2·2 mmol/L (0·6 [SD 1·0] vs 0·5 [0·7]) were similar. Serious adverse events were similar in both groups (eight [0·8%] of 1047 infants in the full milk group vs ten [1·0%] of 1041 infants in the gradual feeding group), all were unrelated to trial intervention.</p><p dir="ltr">Interpretation</p><p dir="ltr">In infants born at 30+0 weeks to 32+6 weeks of gestation, full milk feeds from day 1 does not alter length of hospital stay. It does not increase the risk of necrotising enterocolitis or hypoglycaemia.</p>