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NCT Number: NCT06266455

Individualized Nutrition to Optimize Preterm Infant Growth and Neurodevelopment

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.

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Key information

Conditions

Very Preterm Maturity of Infant Very Low Birth Weight Infant

Age range

Up to 4 week

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Children's National Hospital

Washington D.C., District of Columbia, 20010, United States

Location status: Recruiting

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Standardized Fortification

Dietary Supplement

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

Adjustable Fortification

Dietary Supplement

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

Primary outcomes

  1. Weight Gain Velocity

    Time frame: Study enrollment through nutritional intervention endpoint (term-equivalent age (40 weeks PMA [postmenstrual age]) or discharge home, whichever is achieved first)

    Weight gain velocity (grams per kilogram per day)

  2. Length Growth Velocity

    Time frame: Study enrollment through nutritional intervention endpoint (term-equivalent age (40 weeks PMA [postmenstrual age]) or discharge home, whichever is achieved first)

    Length growth velocity (centimeters per week)

  3. Head Circumference Growth Velocity

    Time frame: Study enrollment through nutritional intervention endpoint (term-equivalent age (40 weeks PMA [postmenstrual age]) or discharge home, whichever is achieved first)

    Head circumference growth velocity (centimeters per week)

  4. Total and Regional Brain Volumes

    Time frame: Term-equivalent age (38 to 41 weeks postmenstrual age)

    Total and regional (cortical and deep gray matter, white matter, amygdala-hippocampus, brainstem, cerebellum) brain volumes by MRI

  5. Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS)

    Time frame: Term-equivalent age (38 to 41 weeks postmenstrual age)

    Summary scores in 13 different domains (habituation, attention, handling, self-regulation, arousal, excitability, lethargy, hypertonicity, hypotonicity, non-optimal reflex, asymmetric reflex, quality of movement, stress)

  6. Mullen Scales of Early Learning (MSEL)

    Time frame: 18 months corrected age

    Composite score as well as 5 subscores: gross motor, fine motor, visual reception, receptive language, and expressive language (reported as standardized t-scores, higher score indicates a better outcome, mean standardized t-score of 50 with standard deviation of 10)

  7. Mullen Scales of Early Learning (MSEL)

    Time frame: 36 months (3 years) of age

    Composite score as well as 5 subscores: gross motor, fine motor, visual reception, receptive language, and expressive language (reported as standardized t-scores, higher score indicates a better outcome, mean standardized t-score score of 50 with standard deviation of 10)

  8. Wechsler Preschool and Primary Scale of Intelligence (4th edition) (WPPSI-IV)

    Time frame: 60 months (5 years) of age

    Five primary indices: verbal comprehension, visual spatial, working memory, fluid reasoning, and processing speed (higher score indicates better performance, score range 40 to 160)

  9. Differential Abilities Scale (2nd edition)-(DAS-II)

    Time frame: 60 months (5 years) of age

    *For children with significant delays who may be unable to reach basal scores on the WPPSI-IV

    Early years core battery: verbal, nonverbal, and spatial reasoning subtests (higher score indicates better performance, score range 40-170)

Interested in participating?

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Sponsors and collaborators

Lead sponsor

Children's National Research Institute

Other

Registry information

Official study title

Transforming Health and Resilience Via Individualized Nutrition in Very Preterm Infants for Extrauterine Growth and Development

Acronym: THRIVE

Important dates

Study start
2024
Primary completion
2034
Study completion
2034
First posted
Feb 20, 2024
Registry last updated
Jul 11, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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