Individualized Nutrition to Optimize Preterm Infant Growth and Neurodevelopment
Purpose
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
Eligibility
- Eligible Ages
- Under 4 Weeks
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Birth gestational age (GA) of ≤32 weeks - Postnatal age ≤4 weeks at time of enrollment - Maternal plan to provide human milk to infant, and consent to providing donor human milk if insufficient maternal milk supply - Maternal age > 18 years old
Exclusion Criteria
- Formula feeding prior to 36 weeks PMA or discharge home (whichever achieved first), either secondary to parental preference or medical necessity - Dysmorphic features or congenital anomalies suggestive of a genetic syndrome, metabolic disorder, chromosomal abnormality, or congenital infection - Dysgenetic or major destructive brain lesions detected by head ultrasound before enrollment
Study Design
- Phase
- N/A
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- Prospective, randomized-controlled trial comparing the impact of individualized human milk fortification on somatic growth and neurodevelopment in preterm infants randomized to receive one of three nutritional interventions: standardized (control), adjustable, or targeted human milk fortification.
- Primary Purpose
- Supportive Care
- Masking
- Single (Outcomes Assessor)
- Masking Description
- Due to the nature of the nutritional interventions, the clinical and research teams will not be blinded to study intervention. The radiologist and research team members performing MRI interpretation, post-acquisition processing, and quantitative analysis will be blinded to study nutritional intervention arm. Similarly, teams performing neurodevelopmental follow-up will also be blinded to study nutritional intervention arm.
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Active Comparator Standardized Fortification |
All study participants will undergo feed advancement and fortification with liquid, bovine-based human milk fortifier (HMF) to an assumed human milk content of 24kcal/oz per the Children's National Hospital NICU standardized clinical feeding protocol. The same milk fortification recipes are utilized for mother's own milk (MOM) and donor human milk (DHM). Each infant's growth trajectory is monitored (weight, length, and head circumference) with dietary modifications performed as needed based on growth parameters. Growth failure is defined as a decline in weight-for-age z-score by greater than 1 standard deviation (>1 SD) beginning 1 week after reaching goal fortified feeds. For infants who demonstrate growth failure, Step 1 will be to add medium chain triglyceride (MCT) oil. If growth remains sub-optimal, Step 2 will be to add liquid protein. |
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|
Experimental Adjustable |
Adjustable fortification will begin 1 week after tolerating goal feeds of standardized fortification. Blood urea nitrogen (BUN) level as a marker of protein metabolism will be measured weekly, and supplementation with liquid protein will be adjusted as necessary to maintain a goal BUN level between 9-14mmol/dL, up to a maximum assumed protein intake of 4.5 g/kg/day. Liquid protein supplementation will be modified as follows: - BUN Level <9 mmol/dL: Increase by 0.5g/kg/day - BUN Level 9-14 mmol/dL: No change - BUN Level >14 mmol/dL: Decrease by 0.25g/kg/day - BUN Level >20 mmol/dL: Hold for 1 week and re-assess Growth failure is defined as a decline in weight-for-age z-score by >1 SD beginning 1 week after achieving BUN within goal range from adjustable fortification. For infants who demonstrate growth failure, MCT oil will be added and increased weekly as needed. |
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Experimental Targeted |
Targeted fortification will begin 1 week after tolerating goal feeds of standardized fortification. Additional supplementation with liquid protein and/or MCT oil will be provided based on twice weekly milk analysis using a mid-infrared human milk analyzer in order to meet macronutrient (carbohydrate, protein, lipid) and energy intake goals per pediatric nutrition guidelines (protein 4-4.5g/kg/day, fat 6-8g/kg/day, energy 120-130kcal/kg/day). Growth failure is defined as a decline in weight-for-age z-score by >1 SD beginning 1 week after receiving macronutrient and energy intake within goal range from targeted fortification. For infants with growth failure, total energy intake will be increased with additional protein and/or MCT oil supplementation. Energy intake may be increased weekly as needed. |
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Recruiting Locations
Children's National and nearby locations
Washington, District of Columbia 20010
More Details
- NCT ID
- NCT06266455
- Status
- Recruiting
- Sponsor
- Children's National Research Institute