Clinical trial NCT02372136: Optimizing Individual Nutrition in Preterm Very Low Birth Weight Infants
Official title: Individualizing and Optimizing Nutrition to Prevent Metabolic Syndrome and To Improve Neurodevelopment in Preterm and Small for Gestational Age Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Infant, Premature, Diseases
Infant, Small for Gestational Age
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
Collaborators: name: Children's Medical Center Dallas
name: The Gerber Foundation
First posted: 2015-02-26
Enrollment: 120
Sex: ALL
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In preterm infants fed human milk, milk needs to be fortified to meet nutrient recommendations. Fortification can be 1) standard, 2) individualized (adjusted based on daily human milk nutrient analysis and milk volume), or 3) optimized (adjusted based on growth rate and serum analyses).

The first specific aim will determine whether individualized and optimized nutrition during hospitalization results in improved growth in the neonatal intensive care unit (NICU) in extremely low gestational age (GA) neonates (ELGANs, \<29 weeks) and in small for GA (SGA, birth weight \<10th percentile for GA) preterm infants compared with optimized nutrition.

The second specific aim will determine whether individualized and optimized nutrition in the NICU improves neurodevelopmental outcomes (acquisition of development milestones) and reduces the risk of disproportionate growth (i.e., excess fat) in the NICU and findings suggestive of metabolic syndrome in the first 3 years of life.

Detailed description: Hypotheses:

1. Primary hypothesis: In preterm infants (GA \<29 weeks or GA \<35 weeks and SGA) individualized and optimized nutrition will increase velocity of growth (weight gain velocity by 2 g x kg-1 x day-1 and length velocity by 0.2 cm per week) from birth to 36 weeks of postmenstrual age (GA plus postnatal age) or discharge (whichever comes first) in comparison with optimized nutrition.
2. Secondary hypotheses: Individualized and optimized nutrition will improve neurodevelopmental outcome and reduce the risk of disproportionate growth (excess fat) in the NICU and findings suggestive of metabolic syndrome in the first 3 years of life.

Study design:

Double-blinded randomized controlled trial (RCT): After consent, 150 neonates will be randomized to one of two groups.

Study intervention: Patients will be randomized to either:

1. Control: optimized nutrition: Milk fortification will be based on current recommendations and optimized by adjustment of nutrients once a week based on blood levels of urea nitrogen and albumin and velocity of growth (weight and length).
2. Intervention: Individualized and optimized nutrition: Milk fortification will be optimized as in control neonates. In addition, nutrition will be individualized every day. Milk fortification will be adjusted based on daily measurements of macronutrients in human milk using near-infrared analysis.

Randomization will be done by computer provided by a statistician using random block allocation and stratification by GA and size for age (AGA \[appropriate for GA\] 23-28 weeks, SGA 23-28 weeks and SGA 29-34 weeks). Twins and multiples will be randomized to the same arm of the study.

Eligibility criteria: Inclusion Criteria:

* Preterm infants \<29 weeks GA and SGA infants \<35 weeks GA born at Parkland Health and Hospital System
* Maternal plan to breastfeed or to use milk from the donor milk bank
* From birth to 1 week of life

Exclusion Criteria:

* Patients on comfort care only
* Patients with major congenital abnormalities
* Patients who are too unstable for the first 7 days to have an accurate length measurement

Primary outcomes:
measure: Growth Velocity
timeFrame: 36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first)
measure: Linear Growth Velocity
timeFrame: 36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first)
Secondary outcomes:
measure: Disproportionate Growth (Increased Fat Mass): BMI >90th Centile
timeFrame: 36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first)
measure: Blood Pressure
timeFrame: 36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first)
measure: Hypertension or High Systolic Blood Pressure
timeFrame: at 33-48 months adjusted age
measure: Neurodevelopment
timeFrame: 18-41 months adjusted age (postnatal age corrected for prematurity)
measure: Neurodevelopment
timeFrame: 18-41 months adjusted age (postnatal age corrected for prematurity) 18-41 months adjusted age (postnatal age corrected for prematurity) 18-41 months corrected age 18-41 months
measure: Leptin
timeFrame: 33-48 months adjusted age
measure: Renal Function
timeFrame: 33-48 months adjusted age
measure: Comparison of Weight With Expected Value for Age and Gender
timeFrame: 36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first)
measure: Comparison of Length With Expected Value for Age and Gender
timeFrame: 36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first)
measure: Comparison of Head Size With Expected Value for Age and Gender
timeFrame: 36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first)
measure: Rate of Weight Gain
timeFrame: 36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first)
measure: Rate of Linear Growth
timeFrame: 36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first)
measure: Comparison of Rate of Head Growth With Expected Value for Age and Gender
timeFrame: 36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first)
measure: Body Composition
timeFrame: at 1 year of age and 3 years of age
Other outcomes:
measure: Mortality
timeFrame: 36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first)
measure: Necrotizing Enterocolitis
timeFrame: 36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first)
Locations:
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
Study officials:
affiliation: UT Southwestern Medical Center
name: Luc P Brion, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Brion LP, Rosenfeld CR, Heyne R, Brown LS, Lair CS, Petrosyan E, Jacob T, Caraig M, Burchfield PJ. Optimizing individual nutrition in preterm very low birth weight infants: double-blinded randomized controlled trial. J Perinatol. 2020 Apr;40(4):655-665. doi: 10.1038/s41372-020-0609-1. Epub 2020 Feb 18.