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

Infant, Newborn Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01534481
• Other study ID #: NICHD-NRN-0047
• Secondary ID: U10HD021364U10HD
• Status: Completed
• Phase: Phase 3
• Start date: August 2012
• Est. completion date: November 30, 2021

Study information

• Verified date: January 2023
• Source: NICHD Neonatal Research Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 483
• Est. completion date: November 30, 2021
• Est. primary completion date: November 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 21 Days

Eligibility

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.

Related Conditions & MeSH terms

• Birth Weight
• Body Weight
• Infant, Extremely Low Birth Weight
• Infant, Newborn
• Infant, Small for Gestational Age

Intervention

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

Dietary Supplement:
• Preterm Formula
Preterm Formula determined by center practice.

Locations

Country	Name	City	State
United States	University of New Mexico	Albuquerque	New Mexico
United States	Emory University	Atlanta	Georgia
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Case Western Reserve University, Rainbow Babies and Children's Hospital	Cleveland	Ohio
United States	Research Institute at Nationwide Children's Hospital	Columbus	Ohio
United States	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas
United States	Wayne State University	Detroit	Michigan
United States	Duke University	Durham	North Carolina
United States	RTI International	Durham	North Carolina
United States	University of Texas Health Science Center at Houston	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	University of Iowa	Iowa City	Iowa
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	Stanford University	Palo Alto	California
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Brown University, Women & Infants Hospital of Rhode Island	Providence	Rhode Island
United States	University of Rochester	Rochester	New York

Sponsors (2)

Lead Sponsor	Collaborator
NICHD Neonatal Research Network	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	At 22-26 months corrected age
Secondary	Total Deaths Before Discharge	Infant died before discharge home.	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
Secondary	Late Onset Sepsis (LOS)	Number of infants diagnosed with LOS	From birth to Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Secondary	Necrotizing Enterocolitis (NEC)	Number of infants diagnosed with NEC	From birth to Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Secondary	Death or Necrotizing Enterocolitis (NEC)	A composite outcome that measures the occurrence of death or NEC	From birth to Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
Secondary	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.	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
Secondary	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)	At 22-26 months corrected age
Secondary	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)	At 22-26 months corrected age
Secondary	Moderate to Severe Cerebral Palsy	Number of infants with moderate or severe grade of cerebral palsy	At 22-26 months corrected age
Secondary	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	At 22-26 months corrected age
Secondary	Profound Impairment	Number of infants with profound impairment.	At 22-26 months corrected age
Secondary	Death or Neurodevelopmental Impairment (NDI)	A composite outcome that measures the occurrence of death through 22-26 months or NDI.	At 22-26 months corrected age

External Links

•   NICHD NRN Website
•   NICHD Pregnancy & Perinatology Branch