Individualized Nutrition to Optimize Preterm Infant Growth and Neurodevelopment

Very Low Birth Weight Infant Clinical Trial

— THRIVE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06266455
• Other study ID #: Pro00000615
• Status: Recruiting
• Phase: N/A
• Start date: February 8, 2024
• Est. completion date: January 2034

Study information

• Verified date: June 2024
• Source: Children's National Research Institute
• Contact: Catherine Limperopoulos, Ph.D.
• Phone: 202-476-5293
• Email: CLimpero[@]childrensnational.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: January 2034
• Est. primary completion date: January 2034
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 4 Weeks

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Dietary Supplement:
• Standardized Fortification
Fortification with liquid, bovine-based HMF to assumed human milk content of 24kcal/oz
• Adjustable Fortification
Additional liquid protein supplementation to maintain serum BUN levels within goal range (9-14mmol/dL)
• 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

Locations

Country	Name	City	State
United States	Children's National Hospital	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Children's National Research Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Weight Gain Velocity	Weight gain velocity (grams per kilogram per day)	Study enrollment through nutritional intervention endpoint (term-equivalent age (40 weeks PMA [postmenstrual age]) or discharge home, whichever is achieved first)
Primary	Length Growth Velocity	Length growth velocity (centimeters per week)	Study enrollment through nutritional intervention endpoint (term-equivalent age (40 weeks PMA [postmenstrual age]) or discharge home, whichever is achieved first)
Primary	Head Circumference Growth Velocity	Head circumference growth velocity (centimeters per week)	Study enrollment through nutritional intervention endpoint (term-equivalent age (40 weeks PMA [postmenstrual age]) or discharge home, whichever is achieved first)
Primary	Total and Regional Brain Volumes	Total and regional (cortical and deep gray matter, white matter, amygdala-hippocampus, brainstem, cerebellum) brain volumes by MRI	Term-equivalent age (38 to 41 weeks postmenstrual age)
Primary	Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS)	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)	Term-equivalent age (38 to 41 weeks postmenstrual age)
Primary	Mullen Scales of Early Learning (MSEL)	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)	18 months corrected age
Primary	Mullen Scales of Early Learning (MSEL)	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)	36 months (3 years) of age
Primary	Wechsler Preschool and Primary Scale of Intelligence (4th edition) (WPPSI-IV)	Five primary indices: verbal comprehension, visual spatial, working memory, fluid reasoning, and processing speed (higher score indicates better performance, score range 40 to 160)	60 months (5 years) of age
Primary	Differential Abilities Scale (2nd edition)-(DAS-II)	*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)	60 months (5 years) of age