Clinical trial NCT06266455: Individualized Nutrition to Optimize Preterm Infant Growth and Neurodevelopment
Official title: Transforming Health and Resilience Via Individualized Nutrition in Very Preterm Infants for Extrauterine Growth and Development
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Very Preterm Maturity of Infant
Very Low Birth Weight Infant
Keywords: Magnetic Resonance Imaging
Neurodevelopment
Nutrition
Fortification
Lead sponsor: Children's National Research Institute
Sponsor class: OTHER
First posted: 2024-02-20
Enrollment: 150
Sex: ALL
Maximum age (years): 4
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Weight Gain Velocity
timeFrame: Study enrollment through nutritional intervention endpoint (term-equivalent age (40 weeks PMA [postmenstrual age]) or discharge home, whichever is achieved first)
measure: Length Growth Velocity
timeFrame: Study enrollment through nutritional intervention endpoint (term-equivalent age (40 weeks PMA [postmenstrual age]) or discharge home, whichever is achieved first)
measure: Head Circumference Growth Velocity
timeFrame: Study enrollment through nutritional intervention endpoint (term-equivalent age (40 weeks PMA [postmenstrual age]) or discharge home, whichever is achieved first)
measure: Total and Regional Brain Volumes
timeFrame: Term-equivalent age (38 to 41 weeks postmenstrual age)
measure: Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS)
timeFrame: Term-equivalent age (38 to 41 weeks postmenstrual age)
measure: Mullen Scales of Early Learning (MSEL)
timeFrame: 18 months corrected age
measure: Mullen Scales of Early Learning (MSEL)
timeFrame: 36 months (3 years) of age
measure: Wechsler Preschool and Primary Scale of Intelligence (4th edition) (WPPSI-IV)
timeFrame: 60 months (5 years) of age
measure: Differential Abilities Scale (2nd edition)-(DAS-II)
timeFrame: 60 months (5 years) of age
Secondary outcomes:
Other outcomes:
Locations:
city: Washington
country: United States
facility: Children's National Hospital
state: District of Columbia
Study officials:
References: