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

Overview

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.

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

Primary outcome measures

• 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)]
• 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)]
• 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)]
• Total and Regional Brain Volumes [Time frame: Term-equivalent age (38 to 41 weeks postmenstrual age)]
• Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) [Time frame: Term-equivalent age (38 to 41 weeks postmenstrual age)]
• Mullen Scales of Early Learning (MSEL) [Time frame: 18 months corrected age]
• Mullen Scales of Early Learning (MSEL) [Time frame: 36 months (3 years) of age]
• Wechsler Preschool and Primary Scale of Intelligence (4th edition) (WPPSI-IV) [Time frame: 60 months (5 years) of age]
• Differential Abilities Scale (2nd edition)-(DAS-II) [Time frame: 60 months (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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Supportive care

Study locations

United States · 1 center

• Children's National Hospital — Washington D.C.

Identifiers

NCT: NCT06266455 · Pro00000615

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗