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

Phase 3

Completed

Conditions: Infant, Extremely Low Birth Weight
Infant, Newborn
Infant, Small for Gestational Age

Interventions: Dietary Supplement: Preterm Formula
Biological: Donor Milk

Registration Number: NCT01534481

Lead Sponsor: NICHD Neonatal Research Network

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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 483

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Preterm Formula	Preterm Formula	Preterm formula determined by center practice
Donor Milk	Donor Milk	Donor milk provided by the Human Milk Banking Association of North America

Primary Outcome Measures

Name	Time	Method
Bayley Scales of Infant Development (BSID) Cognitive Composite Score	At 22-26 months corrected age	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)

Secondary Outcome Measures

Name	Time	Method
Profound Impairment	At 22-26 months corrected age	Number of infants with profound impairment.
Death or Neurodevelopmental Impairment (NDI)	At 22-26 months corrected age	A composite outcome that measures the occurrence of death through 22-26 months or NDI.
Change in Weight-for-age Z-score During 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	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.
Bayley Scales of Infant Development (BSID) Motor Composite Score	At 22-26 months corrected age	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)
Moderate to Severe Cerebral Palsy	At 22-26 months corrected age	Number of infants with moderate or severe grade of cerebral palsy
Total Deaths Before Discharge	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	Infant died before discharge home.
Bayley Scales of Infant Development (BSID) Language Composite Score	At 22-26 months corrected age	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)
Late Onset Sepsis (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	Number of infants diagnosed with LOS
Death or Necrotizing Enterocolitis (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	A composite outcome that measures the occurrence of death or NEC
Necrotizing Enterocolitis (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	Number of infants diagnosed with NEC
Neurodevelopmental Impairment (NDI).	At 22-26 months corrected age	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

Trial Locations

Locations (17): Brown University, Women & Infants Hospital of Rhode Island
🇺🇸
Providence, Rhode Island, United States
University of New Mexico
🇺🇸
Albuquerque, New Mexico, United States
Stanford University
🇺🇸
Palo Alto, California, United States
University of Iowa
🇺🇸
Iowa City, Iowa, United States
Emory University
🇺🇸
Atlanta, Georgia, 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 Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
University of Texas Southwestern Medical Center at Dallas
🇺🇸
Dallas, Texas, United States
University of Texas Health Science Center at Houston
🇺🇸
Houston, Texas, United States
Indiana University
🇺🇸
Indianapolis, Indiana, United States
RTI International
🇺🇸
Durham, North Carolina, United States
Duke University
🇺🇸
Durham, North Carolina, United States
University of Rochester
🇺🇸
Rochester, New York, United States
University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
Wayne State University
🇺🇸
Detroit, Michigan, United States
Children's Mercy Hospital
🇺🇸
Kansas City, Missouri, United States