Manuscript citation:

Ojha S, Mitchell EJ, Johnson MJ, Gale C, McGuire W, Oddie S et al. Full exclusively enteral fluids from day 1 versus gradual feeding in preterm infants (FEED1): an open-label, parallel-group, multicentre, randomised, superiority trial. The Lancet Child & Adolescent Health. 2025 Dec 1;9(12):827-36. PMID 41115446

Reviewed By:

Dr. Kuldeep Singh, D.M
Assistant Professor, Department of Pediatrics, Maharishi Markandeshwar College of Medical Science & Research (MMCMSR), Ambala, Haryana, India- 134003
Email: kuldeepkk9@gmail.com

Type of Investigation:

Prevention

Question:

In infants born at 30 weeks and 0 days (30+⁰ weeks) to 32+⁶ weeks of gestation (P), does exclusively enteral fluids (I) (ie, full milk feeds) from day 1 compared with gradual feeding supplemented with intravenous fluids or parenteral nutrition (C) reduces the length of hospital stay (O)?

METHODS:

Design: Multi-centre, open, parallel group, randomized (1:1) controlled superiority trial
Allocation: The mothers were randomly assigned (1:1) via a secure web-based system to either the full milk group or the gradual milk group.
Blinding: Parents and the clinical team could not be masked, but investigators and data analysts were masked until after database lock
Follow-up period: Primary outcome assessed at the time of discharge
Setting: Recruitment was from 46 neonatal units in UK National Health Service hospitals across England, Scotland, and Wales.
Patients:
Inclusion criteria:
(i) Infants born at 30+0 to 32+6 weeks gestation (inclusive)
(ii) Infants < 3 h (180 min) old (since recorded time of birth)
Exclusion criteria:
(i) Infants with known congenital abnormalities of the gastrointestinal tract or other congenital conditions that make enteral feeding unsafe
(ii) Infants who were small for gestational age (SGA) (birth weight < 10th centile) and have evidence of reversed end-diastolic flow on antenatal umbilical artery Doppler ultrasound and
(iii) Mothers who had participated in the trial during a previous pregnancy.

Intervention:

For infants in the full milk group, milk feeds were started 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. For those in the gradual feeding group, intravenous fluids or parenteral nutrition and small volumes of milk feeds (maximum of 30 mL/kg per day on day 1) were started according to local standard practice.

Outcomes:

Primary outcome: The primary outcome was length of hospital stay, which included the total duration in any neonatal unit measured from day of birth to the day of discharge home.
Secondary outcomes:
Key secondary outcomes were survival, incidence of necrotising enterocolitis (defined as Bell’s stage 2 or 3), incidence of microbiologically confirmed or clinically suspected late-onset sepsis, hypoglycaemia, and breastfeeding own mother’s milk up to hospital discharge.
Analysis and Sample Size: Analysis was intention-to-treat and sample size was 2088 (1047 full milk feeds, 1041 gradual feeding)
Patient follow-up: 100% included in intention-to-treat analysis

MAIN RESULTS:

Between Oct 15, 2019, and July 14, 2024, 2088 infants (1047 full milk feeds, 1041 gradual feeding) were enrolled. 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. Primary outcome data were missing for 18 infants in each group. There was 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.

CONCLUSION:

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.

COMMENTARY:

The FEED1 Trial: When Process Improvement Doesn’t Equal Faster Discharge

The FEED1 trial by Ojha and colleagues represents a major contribution to neonatal research, reporting the largest randomized controlled trial of early full enteral feeding in preterm infants to date, with 2088 infants enrolled across 46 UK neonatal units.1 Though the primary outcome—length of hospital stay—was not reduced, findings challenge how we define clinical “success” and illuminate the multifactorial determinants of discharge in preterm neonates.

A Paradox That Reveals the Truth

The trial demonstrates a striking paradox: infants receiving full milk feeds reached full enteral nutrition 68% faster, required 1.5 fewer days of parenteral nutrition, had fewer invasive procedures, and spent one day less in intensive care—yet hospital length of stay remained unchanged (32.3 vs 32.1 days).1 This disconnect is telling. Even “time to objective discharge criteria” (23 days in both groups) revealed substantial discordance with actual discharge, representing a 9-day gap.1
What the trial inadvertently measured was not feeding practices’ effect on discharge readiness, but institutional discharge practices’ immutability. In the UK NHS context, social, logistical, or administrative factors—not medical readiness—predominantly determine discharge timing for stable moderate-to-late preterm infants.2 The feeding intervention successfully changed medical care but couldn’t overcome non-medical barriers to discharge.

The Challenge of Intervention Fidelity

The pragmatic design, whilst enhancing generalizability, introduces caveats about what was actually tested. Only 61.5% of infants allocated to full milk feeds received ≤24 hours of intravenous fluids, and merely 20.4% were truly exclusively enterally fed from birth.1 Non-adherence reached 39%, primarily due to perceived “feed intolerance” (12.4%)—a subjective assessment in an unmasked trial.
This raises a critical question: Did the trial compare full versus gradual feeding, or “attempted full feeding with frequent deviation to gradual feeding” versus gradual feeding? Substantial non-adherence likely underestimates the true effect of successfully implemented exclusive enteral nutrition.

Redefining Success in Neonatal Care

Should we consider FEED1 a “negative trial”? Absolutely not. The secondary outcomes reveal clinically meaningful benefits. Reduction in central line days (-0.87 days, ~40%) and parenteral nutrition duration (-1.52 days ~56%) represent substantial decreases in invasive interventions, costs, and infection risk exposure.1 Infants also transitioned out of intensive care one day earlier.

 

These findings suggest that early full enteral feeding improves neonatal care quality through reduced medicalization, even without shortening total hospital stay.

 

The subgroup analysis of 242 small-for-gestational-age infants revealed zero necrotizing enterocolitis cases in those receiving full milk feeds.1 While possibly chance in an underpowered group, it contradicts traditional concerns about aggressive feeding in growth-restricted infants and merits dedicated investigation.3

 

Critical questions remain unanswered: What is the optimal strategy for the 39% who did not tolerate full feeds? Can standardized feed intolerance criteria improved intervention fidelity? Does this approach benefit infants <30weeks or <1000g, who face higher NEC risk but might gain more from avoiding parenteral nutrition?4,5

The Path Forward

Rather than viewing FEED1 trial’s null primary outcome as disappointing, we should recognize it as paradigm-shifting evidence that feeding practices are not rate-limiting step for hospital discharge in this population. The path forward requires identifying and addressing true barriers to timely discharge, valuing de-medicalization as important outcomes, and refining protocols for infants who do not tolerate aggressive feeding.

 

The awaited 24-month neurodevelopmental follow-up and health economics analyses will be critical comprehensive interpretation. Meanwhile, FEED1 provides high-quality evidence that stable moderate-to-late preterm infants can be safely fed full milk feeds from birth, with meaningful reductions in medical intervention—an achievement worthy of celebration, even if babies don’t go home faster.

References:

1. Ojha S, Mitchell EJ, Johnson MJ, et al. Full exclusively enteral fluids from day 1 versus gradual feeding in preterm infants (FEED1): an open-label, parallel-group, multicentre, randomized, superiority trial. Lancet Child Adolesc Health 2025; published online Oct 17. doi: 10.1016/S2352-4642(25)00271-8
2. Seaton SE, Barker L, Draper ES, et al. Estimating neonatal length of stay for babies born very preterm. Arch Dis Child Fetal Neonatal Ed. 2019; 104:F182-F186. doi:10.1136/archdischild-2017-314405
3. Battersby C, Longford N, Mandalia S, Costeloe K, Modi N; UK Neonatal Collaborative Necrotising Enterocolitis (UKNC-NEC) study group. Incidence and enteral feed antecedents of severe neonatal necrotising enterocolitis across neonatal networks in England, 2012-13: a whole-population surveillance study. Lancet Gastroenterol Hepatol. 2017; 2:43-51. doi:10.1016/S2468-1253(16)30117-0
4. Dorling J, Abbott J, Berrington J, et al. Controlled Trial of Two Incremental Milk-Feeding Rates in Preterm Infants. N Engl J Med. 2019; 381:1434-43. doi:10.1056/NEJMoa1816654
5. Walsh V, Brown JVE, Copperthwaite BR, Oddie SJ, McGuire W. Early full enteral feeding for preterm or low birth weight infants. Cochrane Database Syst Rev. 2020; 12:CD013542. doi: 10.1002/14651858.CD013542.pub2