Individualized Nutrition to Optimize Preterm Infant Growth and Neurodevelopment

Summary

Human milk has several well-established benefits but does not adequately meet the increased nutritional demands of the growing preterm infant, necessitating additional nutrient supplementation in a process known as fortification. In U.S. neonatal intensive care units (NICUs), human milk is primarily supplemented using standardized fortification, in which a multicomponent fortifier is added to human milk to achieve assumed nutrient content based on standard milk reference values. However, this method does not account for the significant variability in human milk composition or in preterm infant metabolism, and up to half of all very premature infants experience poor growth and malnutrition using current nutritional practices. Poor postnatal growth has adverse implications for the developing preterm brain and long-term neurodevelopment.

Recent advances allow for individualized methods of human milk fortification, including adjustable and targeted fortification. Adjustable fortification uses laboratory markers of protein metabolism (BUN level) to estimate an infant's protein requirements. In targeted fortification, a milk sample is analyzed to determine its specific macronutrient and energy content, with additional macronutrient supplementation provided as needed to achieve goal values. Emerging data suggest that both methods are safe and effective for improving growth, however information on their comparable efficacy and neurodevelopmental implications are lacking, particularly using advanced quantitative brain MRI (qMRI) techniques.

Through this prospective, randomized-controlled trial, the investigators will compare the impact of individualized human milk fortification on somatic growth and neurodevelopment in preterm infants. Infants will be randomized to receive one of three nutritional interventions: standardized (control group), adjustable, or targeted human milk fortification. Infants will undergo their assigned nutritional intervention until term-equivalent age or discharge home, whichever is achieved first. Brain qMRI will be performed at term-corrected age, and neurodevelopmental follow-up will be performed through 5 years of age.

Conditions

• Very Preterm Maturity of Infant
• Very Low Birth Weight Infant

Interventions

DIETARY_SUPPLEMENT

Standardized Fortification

Fortification with liquid, bovine-based HMF to assumed human milk content of 24kcal/oz

DIETARY_SUPPLEMENT

Adjustable Fortification

Additional liquid protein supplementation to maintain serum BUN levels within goal range (9-14mmol/dL)

DIETARY_SUPPLEMENT

Adjustable Fortification

Additional liquid protein and/or MCT oil supplementation to maintain protein, fat, and energy intake within goal range based upon mid-infrared human milk analysis

Sponsors & Collaborators

• Children's National Research Institute

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

SUPPORTIVE_CARE

Masking

SINGLE

Model

PARALLEL

Eligibility

Max Age

4 Weeks

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-02-08

Primary Completion

2034-01-31

Completion

2034-01-31

Countries

• United States

Study Locations