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

Sponsor

NICHD Neonatal Research Network (Other)

Overall Status

Completed

CT.gov ID

NCT01534481

Collaborator

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

483

Enrollment

Locations

Arms

111.5

Actual Duration (Months)

28.4

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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

Study Type:

Interventional

Actual Enrollment :

483 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 :

Aug 1, 2012

Actual Primary Completion Date :

Nov 15, 2021

Actual Study Completion Date :

Nov 15, 2021

Arms and Interventions

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.

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

Primary Outcome Measures

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

Secondary Outcome Measures

In Hospital Morbidities [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
Growth outcomes [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.
Follow-up Outcomes [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

Criteria

Ages Eligible for Study:

N/A to 21 Days

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35233
2	Stanford University	Palo Alto	California	United States	94304
3	Emory University	Atlanta	Georgia	United States	30303
4	Indiana University	Indianapolis	Indiana	United States	46202
5	University of Iowa	Iowa City	Iowa	United States	52242
6	Wayne State University	Detroit	Michigan	United States	48201
7	Children's Mercy Hospital	Kansas City	Missouri	United States	64108
8	University of New Mexico	Albuquerque	New Mexico	United States	87131
9	University of Rochester	Rochester	New York	United States	14642
10	RTI International	Durham	North Carolina	United States	27705
11	Duke University	Durham	North Carolina	United States	27710
12	Case Western Reserve University, Rainbow Babies and Children's Hospital	Cleveland	Ohio	United States	44106
13	Research Institute at Nationwide Children's Hospital	Columbus	Ohio	United States	43205
14	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
15	Brown University, Women & Infants Hospital of Rhode Island	Providence	Rhode Island	United States	02905
16	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas	United States	75235
17	University of Texas Health Science Center at Houston	Houston	Texas	United States	77030

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