Evidence map›Paper›PMID 39239939›Full record

SynthesisThe Cochrane database of systematic reviews2024

Donor human milk for preventing necrotising enterocolitis in very preterm or very low-birthweight infants.

Maria Quigley, Nicholas D Embleton, Nicholas Meader, William McGuire

Registry-linked trialAbstract readMeta-AnalysisSystematic Review
In one paragraph

Synthesis in The Cochrane database of systematic reviews, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06893939 (Limited Versus Extended Trophic Feeding), which is not on this map. Cited by 54 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed, 5 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT06893939 phase2 / phase3recruitingnot on this mapstarted 2025, after this paper: background citation

Limited Versus Extended Trophic Feeding (LET-FEED) Trial

TypeinterventionalSponsorUniversity of WashingtonRan2025 to 2031Enrolled350ConditionsSepsis, Length of Stay, Mortality, Neurodevelopmental DelayArmsLimited Trophic Feeds (1 day of trophic feeds), Extended Trophic Feeds (3 days of trophics)
3 · Its place in the literature

Who cites it

54 citing papers in PubMed, 5 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
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  5. Pooled it
  6. Trial
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  8. Article
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  11. Review
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  13. Balancing access to donor human milk: Rationing vs expanding use.Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition · 2026
    Review
  14. Review
  15. Comparing necrotizing enterocolitis risk among extremely preterm infants by use of human-milk or bovine-milk-based fortifier.Journal of perinatology : official journal of the California Perinatal Association · 2026
    Article
  16. Article
  17. Article
  18. Impact of fortifiers on donor milk nutrient composition: An experimental study.JPEN. Journal of parenteral and enteral nutrition · 2026
    Article
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors.

Maria QuigleyNational Perinatal Epidemiology Unit, University of Oxford, Oxford, UK.
Nicholas D EmbletonNewcastle Neonatal Service , Newcastle Hospitals NHS Foundation Trust and Newcastle University, Newcastle upon Tyne, UK.
Nicholas MeaderUniversity of Newcastle, Newcastle upon Tyne, UK.
William McGuireCentre for Reviews and Dissemination , University of York, York, UK.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundWhen sufficient maternal milk is not available, donor human milk or formula are the alternative forms of enteral nutrition for very preterm or very low-birthweight (VLBW) infants. Donor human milk may retain the non-nutritive benefits of maternal milk and has been proposed as a strategy to reduce the risk of necrotising enterocolitis (NEC) and associated mortality and morbidity in very preterm or VLBW infants.

objectivesTo assess the effectiveness of donor human milk compared with formula for preventing NEC and associated morbidity and mortality in very preterm or VLBW infants when sufficient maternal milk is not available. SEARCH

methodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Maternity and Infant Care (MIC) database, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), from the earliest records to February 2024. We searched clinical trials registries and examined the reference lists of included studies. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials comparing feeding with donor human milk versus formula in very preterm (< 32 weeks' gestation) or VLBW (< 1500 g) infants. DATA COLLECTION AND ANALYSIS: Two review authors evaluated the risk of bias in the trials, extracted data, and synthesised effect estimates using risk ratio, risk difference, and mean difference, with associated 95% confidence intervals. The primary outcomes were NEC, late-onset invasive infection, and all-cause mortality before hospital discharge. The secondary outcomes were growth parameters and neurodevelopment. We used the GRADE approach to assess the certainty of the evidence for our primary outcomes. MAIN

resultsTwelve trials with a total of 2296 infants fulfilled the inclusion criteria. Most trials were small (average sample size was 191 infants). All trials were performed in neonatal units in Europe or North America. Five trials were conducted more than 40 years ago; the remaining seven trials were conducted in the year 2000 or later. Some trials had methodological weaknesses, including concerns regarding masking of investigators and selective reporting. Meta-analysis showed that donor human milk reduces the risk of NEC (risk ratio (RR) 0.53, 95% confidence interval (CI) 0.37 to 0.76; I² = 4%; risk difference (RD) -0.03, 95% CI -0.05 to -0.01; 11 trials, 2261 infants; high certainty evidence). Donor human milk probably has little or no effect on late-onset invasive infection (RR 1.12, 0.95 to 1.31; I² = 27%; RD 0.03, 95% CI -0.01 to -0.07; 7 trials, 1611 infants; moderate certainty evidence) or all-cause mortality (RR 1.00, 95% CI 0.76 to 1.31; I² = 0%; RD -0.00, 95% CI -0.02 to 0.02; 9 trials, 2116 infants; moderate certainty evidence). AUTHORS'

conclusionsThe evidence shows that donor human milk reduces the risk of NEC by about half in very preterm or VLBW infants. There is probably little or no effect on late-onset invasive infection or all-cause mortality before hospital discharge.

Indexed as

Enterocolitis, NecrotizingInfant, Very Low Birth WeightMilk, HumanBiasEnteral NutritionHumansInfant, Extremely PrematureInfant FormulaInfant, NewbornInfant, PrematureInfant, Premature, DiseasesRandomized Controlled Trials as Topic

Identifiers

PMID39239939
PMCPMC11378496

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.