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.
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
- Conditions the study is for
- Infant, Newborn, Infant, Small for Gestational Age, Infant, Extremely Low Birth Weight
- 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
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
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- 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
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 group | Role | What they receive |
|---|---|---|
| Donor Milk | Active comparator | Donor milk provided by the Human Milk Banking Association of North America Receives: Biological: Donor Milk |
| Preterm Formula | Placebo comparator | Preterm 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.
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)
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
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
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
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
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
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
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
Moderate to Severe Cerebral Palsy
Number of infants with moderate or severe grade of cerebral palsy
Measured: At 22-26 months corrected age
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
Profound Impairment
Number of infants with profound impairment.
Measured: At 22-26 months corrected age
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.
- First posted16 Feb 2012 (estimated)
- Study startAug 2012
- Primary completion30 Nov 2021
- Study completion30 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Infant, NewbornStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- NICHD Neonatal Research Network
- Sponsor type
- Research network
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
- Investigators
- Tarah Colaizy, MD, MPH, Study director, University of IowaMichele C Walsh, MD, Principal investigator, Case Western Reserve University, Rainbow Babies and Children's HospitalSeetha Shankaran, MD, Principal investigator, Wayne State UniversityAbbot R Laptook, MD, Principal investigator, Brown University, Women & Infants Hospital of Rhode IslandC. Michael Cotten, MD, Principal investigator, Duke UniversityDavid Carlton, MD, Principal investigator, Emory UniversityGreg Sokol, MD, Principal investigator, Indiana UniversityAbhik Das, PhD, Principal investigator, RTI International
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
- Results posted
- Yes, on ClinicalTrials.gov
- 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