Clinical trial NCT01534481: Donor Milk vs. Formula in Extremely Low Birth Weight (ELBW) Infants
Official title: Neurodevelopmental Effects of Donor Human Milk vs. Preterm Formula in Extremely Low Birth Weight (ELBW) Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infant, Newborn
Infant, Small for Gestational Age
Infant, Extremely Low Birth Weight
Keywords: NICHD Neonatal Research Network
Extremely Low Birth Weight (ELBW)
Prematurity
Neurodevelopmental Impairment
Donor Breast Milk
Preterm Formula
Lead sponsor: NICHD Neonatal Research Network
Sponsor class: NETWORK
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2012-02-16
Enrollment: 483
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility 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.

Primary outcomes:
measure: Bayley Scales of Infant Development (BSID) Cognitive Composite Score
timeFrame: At 22-26 months corrected age
Secondary outcomes:
measure: Total Deaths Before Discharge
timeFrame: 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
measure: Late Onset Sepsis (LOS)
timeFrame: From birth to Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
measure: Necrotizing Enterocolitis (NEC)
timeFrame: From birth to Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
measure: Death or Necrotizing Enterocolitis (NEC)
timeFrame: From birth to Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth
measure: Change in Weight-for-age Z-score During Study
timeFrame: 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
measure: Bayley Scales of Infant Development (BSID) Motor Composite Score
timeFrame: At 22-26 months corrected age
measure: Bayley Scales of Infant Development (BSID) Language Composite Score
timeFrame: At 22-26 months corrected age
measure: Moderate to Severe Cerebral Palsy
timeFrame: At 22-26 months corrected age
measure: Neurodevelopmental Impairment (NDI).
timeFrame: At 22-26 months corrected age
measure: Profound Impairment
timeFrame: At 22-26 months corrected age
measure: Death or Neurodevelopmental Impairment (NDI)
timeFrame: At 22-26 months corrected age
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Durham
country: United States
facility: RTI International
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: Case Western Reserve University, Rainbow Babies and Children's Hospital
state: Ohio
city: Columbus
country: United States
facility: Research Institute at Nationwide Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Providence
country: United States
facility: Brown University, Women & Infants Hospital of Rhode Island
state: Rhode Island
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center at Dallas
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
Study officials:
affiliation: University of Iowa
name: Tarah Colaizy, MD, MPH
role: STUDY_DIRECTOR
affiliation: Case Western Reserve University, Rainbow Babies and Children's Hospital
name: Michele C Walsh, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Wayne State University
name: Seetha Shankaran, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Brown University, Women & Infants Hospital of Rhode Island
name: Abbot R Laptook, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: C. Michael Cotten, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Emory University
name: David Carlton, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Indiana University
name: Greg Sokol, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: RTI International
name: Abhik Das, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Krisa P Van Meurs, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alabama at Birmingham
name: Waldemar A Carlo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of New Mexico
name: Kristi L Watterberg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Texas, Southwestern Medical Center at Dallas
name: Myra Wyckoff, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The University of Texas Health Science Center, Houston
name: Jon Tyson, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pennsylvania
name: Sara DeMauro, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Rochester
name: Carl T D'Angio, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Research Institute at Nationwide Children's Hospital
name: Pablo J Sanchez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Mercy Hospital Kansas City
name: William Truog, MD
role: PRINCIPAL_INVESTIGATOR
References: