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

NICHD Neonatal Research Network483 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

Conditions

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

Interventions

Donor MilkBIOLOGICAL

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

Preterm FormulaDIETARY_SUPPLEMENT

Preterm Formula determined by center practice.

Eligibility

Sex: ALLMax age: 21 Days

Medical Language ↔ Plain English

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.

Locations (17)

University of Alabama at Birmingham

Birmingham, Alabama, United States

Stanford University

Palo Alto, California, United States

Outcomes

Primary Outcomes

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)

Time frame: At 22-26 months corrected age

Secondary Outcomes

Total Deaths Before Discharge

Infant died before discharge home.

Time frame: 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

Late Onset Sepsis (LOS)

Number of infants diagnosed with LOS

Time frame: From birth to Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth

Necrotizing Enterocolitis (NEC)

Number of infants diagnosed with NEC

Time frame: From birth to Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth

Death or Necrotizing Enterocolitis (NEC)

A composite outcome that measures the occurrence of death or NEC

Time frame: From birth to Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth

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.

Data from ClinicalTrials.gov

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