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

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief 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. 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.

Condition or disease	Intervention/treatment	Phase
Infant, Newborn; Infant, Small for Gestational Age; Infant, Extremely Low Birth Weight	Biological: Donor Milk; Dietary Supplement: Preterm Formula	Phase 3

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	670 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Prevention
Official Title:	Neurodevelopmental Effects of Donor Human Milk vs. Preterm Formula in Extremely Low Birth Weight (ELBW) Infants
Actual Study Start Date :	August 2012
Estimated Primary Completion Date :	June 2019
Estimated Study Completion Date :	June 2020

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Active Comparator: Donor Milk; Donor milk provided by the Human Milk Banking Association of North America	Biological: Donor Milk; Donor milk provided by the Human Milk Banking Association of North America
Placebo Comparator: Preterm Formula; Preterm formula determined by center practice	Dietary Supplement: Preterm Formula; Preterm Formula determined by center practice.

Outcome Measures

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Primary Outcome Measures :

1. Neurodevelopmental Outcome [ Time Frame: 22-26 months corrected age ]
   As measured by scores on Bayley Scales of Infant Development III (BSID III)

Secondary Outcome Measures :

1. In Hospital Morbidities [ Time Frame: Up to one year ]

   These include:

   • Death
   • Late onset sepsis or meningitis
   • Length of TPN use
   • Length of initial hospital stay
   • Necrotizing enterocolitis
   • Bronchopulmonary dysplasia (BPD), defined as room air oxygen saturation of less than 90% at 36 weeks postmenstrual age using the NRN standard physiologic definition of BPD.
   • Necrotizing enterocolitis or death
   • BPD or death
2. Growth outcomes [ Time Frame: 36 Weeks and 22-26 months corrected age ]
   In-Hospital growth parameters, including rate of weight gain, weight, length and head circumference at 36 weeks or discharge, whichever comes first. Weights will be obtained from hospital records weekly, length and head circumference will be measured bi-weekly by study personnel.
3. Follow-up Outcomes [ Time Frame: 22-26 months corrected age ]
   • Number of hospital admissions between initial discharge and follow-up
   • Motor and Language scores on the BSID III
   • Cerebral Palsy
   • Neurodevelopmental Impairment (NDI), using current Follow-Up Study definition.
   • Profound Impairment, defined as BSID III Cognitive subscale score of 70
   • NDI or death
   • Profound Impairment or death

Eligibility Criteria

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Ages Eligible for Study:	up to 21 Days (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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
• 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.

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Contacts

Contact: Tarah Colaizy, MD, MPH	319-356-3508
Contact: Rosemary D Higgins, MD	301-496-5575

Locations

United States, Alabama
University of Alabama at Birmingham	Recruiting
Birmingham, Alabama, United States, 35233
Contact: Waldemar A. Carlo, MD 205-934-4680
Principal Investigator: Waldemar A. Carlo, MD
United States, California
Stanford University	Recruiting
Palo Alto, California, United States, 94304
Contact: Krisa P. Van Meurs, MD
Principal Investigator: Krisa P. Van Meurs, MD
United States, Georgia
Emory University	Recruiting
Atlanta, Georgia, United States, 30303
Contact: David Carlton, MD
Principal Investigator: David Carlton, MD
United States, Indiana
Indiana University	Active, not recruiting
Indianapolis, Indiana, United States, 46202
United States, Iowa
University of Iowa	Recruiting
Iowa City, Iowa, United States, 52242
Contact: Tarah Colaizy, MD, MPH 319-356-3508
Principal Investigator: Edward F. Bell, MD
United States, Michigan
Wayne State University	Active, not recruiting
Detroit, Michigan, United States, 48201
United States, Missouri
Children's Mercy Hospital	Active, not recruiting
Kansas City, Missouri, United States, 64108
United States, New Mexico
University of New Mexico	Recruiting
Albuquerque, New Mexico, United States, 87131
Contact: Kristi L. Watterberg, MD
Principal Investigator: Kristi L. Watterberg, MD
United States, New York
University of Rochester	Recruiting
Rochester, New York, United States, 14642
Contact: Carl T D'Angio, MD 585-273-4911
Principal Investigator: Carl T D'Angio, MD
United States, North Carolina
RTI International	Active, not recruiting
Durham, North Carolina, United States, 27705
Duke University	Recruiting
Durham, North Carolina, United States, 27710
Contact: C. Michael Cotten, MD
Sub-Investigator: C. Michael Cotten, MD MHS
United States, Ohio
Case Western Reserve University, Rainbow Babies and Children's Hospital	Recruiting
Cleveland, Ohio, United States, 44106
Contact: Michele C. Walsh, MD MS
Principal Investigator: Michele C. Walsh, MD MS
Research Institute at Nationwide Children's Hospital	Recruiting
Columbus, Ohio, United States, 43205
Contact: Pablo Sanchez, MD
Principal Investigator: Pablo Sanchez, MD
United States, Pennsylvania
University of Pennsylvania	Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Eric Eichenwald, MD
Principal Investigator: Eric Eichenwald, MD
United States, Rhode Island
Brown University, Women & Infants Hospital of Rhode Island	Recruiting
Providence, Rhode Island, United States, 02905
Contact: Abbot R. Laptook, MD
Principal Investigator: Abbot R. Laptook, MD
United States, Texas
University of Texas Southwestern Medical Center at Dallas	Recruiting
Dallas, Texas, United States, 75235
Contact: Myra Wyckoff, MD
Principal Investigator: Myra Wyckoff, MD
University of Texas Health Science Center at Houston	Recruiting
Houston, Texas, United States, 77030
Contact: Jon E Tyson, MD MPH
Principal Investigator: Jon E. Tyson, MD MPH

Sponsors and Collaborators

NICHD Neonatal Research Network

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

Study Director:	Tarah Colaizy, MD, MPH	University of Iowa
Principal Investigator:	Michele C Walsh, MD	Case Western Reserve University, Rainbow Babies and Children's Hospital
Principal Investigator:	Seetha Shankaran, MD	Wayne State University
Principal Investigator:	Abbot R Laptook, MD	Brown University, Women & Infants Hospital of Rhode Island
Principal Investigator:	C. Michael Cotten, MD	Duke University
Principal Investigator:	David Carlton, MD	Emory University
Principal Investigator:	Greg Sokol, MD	Indiana University
Principal Investigator:	Abhik Das, PhD	RTI International
Principal Investigator:	Krisa P Van Meurs, MD	Stanford University
Principal Investigator:	Waldemar A Carlo, MD	University of Alabama at Birmingham
Principal Investigator:	Kristi L Watterberg, MD	University of New Mexico
Principal Investigator:	Myra Wyckoff, MD	University of Texas, Southwestern Medical Center at Dallas
Principal Investigator:	Jon Tyson, MD, MPH	The University of Texas Health Science Center, Houston
Principal Investigator:	Sara DeMauro, MD	University of Pennsylvania
Principal Investigator:	Carl T D'Angio, MD	University of Rochester
Principal Investigator:	Pablo J Sanchez, MD	Research Institute at Nationwide Children's Hospital
Principal Investigator:	William Truog, MD	Children's Mercy Hospital Kansas City

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

NICHD NRN Website 

NICHD Pregnancy &amp; Perinatology Branch 

Responsible Party:	NICHD Neonatal Research Network
ClinicalTrials.gov Identifier:	NCT01534481 History of Changes
Other Study ID Numbers:	NICHD-NRN-0047; U10HD021364 ( U.S. NIH Grant/Contract ); U10HD040689 ( U.S. NIH Grant/Contract ); U10HD021385 ( U.S. NIH Grant/Contract ); U10HD027851 ( U.S. NIH Grant/Contract ); U10HD027853 ( U.S. NIH Grant/Contract ); U10HD027856 ( U.S. NIH Grant/Contract ); U10HD027904 ( U.S. NIH Grant/Contract ); U10HD027880 ( U.S. NIH Grant/Contract ); U10HD034216 ( U.S. NIH Grant/Contract ); U10HD021373 ( U.S. NIH Grant/Contract ); U10HD040492 ( U.S. NIH Grant/Contract ); U10HD053109 ( U.S. NIH Grant/Contract ); U10HD040461 ( U.S. NIH Grant/Contract ); U10HD068244 ( U.S. NIH Grant/Contract ); U10HD068263 ( U.S. NIH Grant/Contract ); U10HD068278 ( U.S. NIH Grant/Contract ); U10HD068284 ( U.S. NIH Grant/Contract ); U10HD036790 ( U.S. NIH Grant/Contract )
First Posted:	February 16, 2012
Last Update Posted:	November 9, 2017
Last Verified:	November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Yes
Plan Description:	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)

Keywords provided by NICHD Neonatal Research Network:

NICHD Neonatal Research Network; Extremely Low Birth Weight (ELBW); Prematurity	Neurodevelopmental Impairment; Donor Breast Milk; Preterm Formula

Additional relevant MeSH terms:

Body Weight; Birth Weight; Signs and Symptoms