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Infant, NewbornPhase 3NCT01534481

Donor Milk vs. Formula in Extremely Low Birth Weight (ELBW) Infants

A Phase 3 study testing Donor Milk and Preterm Formula in people with Infant, Newborn and Infant, Small for Gestational Age, run by NICHD Neonatal Research Network at 17 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The Milk Trial seeks to determine the effect on neurodevelopmental outcomes at age 22-26 months of donor human milk as compared to preterm infant formula as the in-hospital diet for infants whose mothers choose not to provide breast milk or are able to provide only a minimal amount. Read more about this study

Who is it for?
Ages Up to 21 days
What is being tested?
Donor Milk and Preterm Formula
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
483 participants
Where
17 sitesUnited States
Study dates
Aug 2012to 30 Nov 2021
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 21 days
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Gestational age less than 29 weeks.
  • Admitted to the NICU at less than or equal to 72 hours of life
  • Survived at least 12 hours

Who cannot join

  • Chromosomal anomalies
  • Cyanotic congenital heart disease
  • Diagnosed intrauterine infection
  • Other congenital disorders known to impair neurodevelopment
  • NEC or IP prior to seeking consent
  • Decision documented to limit intensive care therapies
Show all 10Show fewer
  • Congenital disorders that may affect feeding
  • Feeding Group Eligibility:
  • Sole Diet Group: Infants will be eligible for the sole diet feeding protocol if the mother declines to provide breast milk for the baby.
  • Supplemental Diet (minimal maternal milk) Group: Infants whose mothers initially choose to provide breast milk and begin pumping will be re-screened for eligibility at least weekly until the infant is 21 days old. If the mother stops expressing milk at any point prior to the infant's 21st day of life, her infant will be eligible for randomization. In addition, those whose mothers are providing less than 20% of the infant's dietary needs (averaged over past 5 days) when the infant reaches 21 days of age will be eligible for randomization at this point. No infant will be randomized after reaching 21 days.

Trial locations and contacts

17 sites in 1 country.

17 sites in 1 country

United States17 sites

  • University of New Mexico

    Albuquerque, New Mexico, 87131

  • Emory University

    Atlanta, Georgia, 30303

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35233

  • Case Western Reserve University, Rainbow Babies and Children's Hospital

    Cleveland, Ohio, 44106

  • Research Institute at Nationwide Children's Hospital

    Columbus, Ohio, 43205

  • University of Texas Southwestern Medical Center at Dallas

    Dallas, Texas, 75235

  • Wayne State University

    Detroit, Michigan, 48201

  • RTI International

    Durham, North Carolina, 27705

  • Duke University

    Durham, North Carolina, 27710

  • University of Texas Health Science Center at Houston

    Houston, Texas, 77030

  • Indiana University

    Indianapolis, Indiana, 46202

  • University of Iowa

    Iowa City, Iowa, 52242

  • Children's Mercy Hospital

    Kansas City, Missouri, 64108

  • Stanford University

    Palo Alto, California, 94304

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Brown University, Women & Infants Hospital of Rhode Island

    Providence, Rhode Island, 02905

  • University of Rochester

    Rochester, New York, 14642

Other trials in United States

About this study

Official title: Neurodevelopmental Effects of Donor Human Milk vs. Preterm Formula in Extremely Low Birth Weight (ELBW) Infants

The Milk Trial seeks to determine the effect on neurodevelopmental outcomes at age 22-26 months of donor human milk as compared to preterm infant formula as the in-hospital diet for infants whose mothers choose not to provide breast milk or are able to provide only a minimal amount. Infants will be randomized to receive donor breast milk or formula during their hospital stay. Infant's will be followed until they reach 22-26 months of age.

Read the detailed description

There is strong evidence that maternal breast milk feedings in infancy confer multiple health benefits in the extremely preterm population (extremely low birth weight, ELBW, <1000 g). Studies suggest an IQ advantage of up to 8 points conferred by maternal milk feeding in this population. Rates of sepsis and necrotizing enterocolitis are also lower in human milk fed ELBW infants, and they experience shorter hospital stays and fewer re-hospitalizations in the first year of life. When mothers choose not to or are unable to provide milk, preterm formula is usually used. Recently, pasteurized donor human milk is available in some NICUs in the US as an alternative to preterm formula. Donor milk has not been well studied with regard to its safety and efficacy. It is unknown if donor human milk confers the same benefits as maternal milk with regard to neurodevelopmental and health outcomes. The proposed study will be the first US multicenter randomized trial of the health and developmental effects of donor milk as compared to preterm formula in ELBW infants receiving little or no maternal milk. Our long-term goal is to optimize neurodevelopmental and health outcomes for ELBW infants, maximizing their quality of life and societal functionality throughout their lives. If donor human milk has similar effects to maternal milk, the public health benefit of donor milk feedings in ELBW infants unable to receive maternal milk would be considerable.

Being tested
Donor Milk, Preterm Formula
Keywords
NICHD Neonatal Research Network, Extremely Low Birth Weight (ELBW), Prematurity, Neurodevelopmental Impairment, Donor Breast Milk, Preterm Formula
Medical subject headings
Premature Birth

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Donor MilkBiological

    Donor milk provided by the Human Milk Banking Association of North America

  • Preterm FormulaDietary supplement

    Preterm Formula determined by center practice.

Study groups in NCT01534481
Study groupRoleWhat they receive
Donor MilkActive comparatorDonor milk provided by the Human Milk Banking Association of North America
Receives: Biological: Donor Milk
Preterm FormulaPlacebo comparatorPreterm formula determined by center practice
Receives: Dietary Supplement: Preterm Formula

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Bayley Scales of Infant Development (BSID) Cognitive Composite Score

    Mean cognitive composite score (standardized mean 100, SD 15, range 54-145). Subjects who died prior to follow-up assigned the score of 54. (lower scores indicating greater impairment)

    Measured: At 22-26 months corrected age

Secondary outcomes (11)

  1. Total Deaths Before Discharge

    Infant died before discharge home.

    Measured: From day of randomization to Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 1 year following birth

  2. Late Onset Sepsis (LOS)

    Number of infants diagnosed with LOS

    Measured: From birth to Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth

  3. Necrotizing Enterocolitis (NEC)

    Number of infants diagnosed with NEC

    Measured: From birth to Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth

  4. Death or Necrotizing Enterocolitis (NEC)

    A composite outcome that measures the occurrence of death or NEC

    Measured: From birth to Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth

  5. Change in Weight-for-age Z-score During Study

    Weight-for-age Z-scores were calculated at both baseline (study initiation) and study end (within one week of last study data collected) based on Fenton growth curves (2013). This outcome represents the change in weight-for-age Z-score during the course of the study (i.e., the Z-score at baseline was subtracted from the Z-score at study end).

    A value of 0 represents that the infant's weight-for-age Z-score is the same at the beginning and the end of the study. Positive values indicate the increase in the infant's weight-for-age Z-score during the study; negative values indicate the decrease in the infant's weight-for-age Z-score during the study.

    Measured: During Study Intervention, the time between study randomization and discontinuation of study protocol. Infants exited from the study protocol 1-2 weeks prior to anticipated hospital discharge or 120 days, whichever is sooner

  6. Bayley Scales of Infant Development (BSID) Motor Composite Score

    Mean motor composite score (standardized mean 100, range 44-155). Subjects who died prior to follow-up assigned the score of 44. (lower scores indicating greater impairment)

    Measured: At 22-26 months corrected age

  7. Bayley Scales of Infant Development (BSID) Language Composite Score

    Mean language composite score (standardized mean 100, range 46-155). Subjects who died prior to follow-up assigned the score of 46. (lower scores indicating greater impairment)

    Measured: At 22-26 months corrected age

  8. Moderate to Severe Cerebral Palsy

    Number of infants with moderate or severe grade of cerebral palsy

    Measured: At 22-26 months corrected age

  9. Neurodevelopmental Impairment (NDI).

    Number of infants with NDI. NDI is defined as any of the following: Gross Motor Function Classification System score greater than or equal to 2, Bayley III cognitive or motor score less than 85 (1 standard deviation), Vision Impairment or Hearing impairment

    Measured: At 22-26 months corrected age

  10. Profound Impairment

    Number of infants with profound impairment.

    Measured: At 22-26 months corrected age

  11. Death or Neurodevelopmental Impairment (NDI)

    A composite outcome that measures the occurrence of death through 22-26 months or NDI.

    Measured: At 22-26 months corrected age

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Feb 2012 (estimated)
  2. Study startAug 2012
  3. Primary completion30 Nov 2021
  4. Study completion30 Nov 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
483 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01534481
Sponsor's protocol ID
NICHD-NRN-0047
Other IDs
U10HD021364, U10HD040689, U10HD021385, U10HD027851, U10HD027853, U10HD027856, U10HD027904, U10HD027880
Status last verified
Jun 2026
First submitted
13 Feb 2012
Last updated
16 Jul 2026
Data monitoring committee
Yes
Individual data sharing
Yes: NIH has had a long-standing policy to share and make available to the public the results and accomplishments of the activities that it funds. The NRN plans to share de-identified data after final publication in an NIH supported data repository such as the NICHD Data and Specimen Hub (https://dash.nichd.nih.gov)

Publications

  • Colaizy TT, Poindexter BB, McDonald SA, Bell EF, Carlo WA, Carlson SJ, DeMauro SB, Kennedy KA, Nelin LD, Sanchez PJ, Vohr BR, Johnson KJ, Herron DE, Das A, Crawford MM, Walsh MC, Higgins RD, Stoll BJ; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network; MILK Trial Investigators; Ambalavanan N, Wyckoff MH, D'Angio CT, Bugg GW, Ohls RK, Reynolds AM, Sokol GM, Laptook AR, Olsen SL, White JR, Jadcherla SR, Bajaj M, Parimi PS, Schmidt B, Laughon MM, Barks J, Fisher KA, Hibbs AM, Peralta-Carcelen M, Cook N, Heyne RJ, Cavanaugh B, Adams-Chapman I, Fuller J, Hartley-McAndrew ME, Harmon HM, Duncan AF, Hines AC, Kilbride HW, Richards LA, Maitre NL, Natarajan G, Trembath AN, Carlson MD, Malcolm WF, Wilson-Costello DE; MILK Trial Investigators; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Neurodevelopmental Outcomes of Extremely Preterm Infants Fed Donor Milk or Preterm Infant Formula: A Randomized Clinical Trial. JAMA. 2024 Feb 20;331(7):582-591. doi: 10.1001/jama.2023.27693.

    PubMed 38497706

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Donor Milk and Preterm Formula in people with Infant, Newborn and Infant, Small for Gestational Age, run by NICHD Neonatal Research Network at 17 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Bayley Scales of Infant Development (BSID) Cognitive Composite Score (time frame: At 22-26 months corrected age). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01534481, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jul 2026.

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