Optimizing Individual Nutrition in Preterm Very Low Birth Weight Infants

Not Applicable

Completed

• Conditions: Infant, Small for Gestational Age; Infant, Premature, Diseases
• Interventions: Dietary Supplement: Individualized Nutrition; Dietary Supplement: Optimized nutrition

• Registration Number: NCT02372136
• Lead Sponsor: University of Texas Southwestern Medical Center

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2015-02-12
• Study First Submitted QC: 2015-02-19
• Study First Posted: 2015-02-26
• Study Start: 2016-01
• Results First Submitted: 2021-03-05
• Results First Submitted QC: 2021-04-28
• Results First Posted: 2021-05-20
• Primary Completion: 2023-12-31
• Study Completion: 2023-12-31
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-07
• Last Update Posted: 2024-07-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 120

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Individualized and Optimized Nutrition	Individualized Nutrition	Individualized nutrition Optimized nutrition
Optimized Nutrition	Optimized nutrition	Optimized nutrition
Individualized and Optimized Nutrition	Optimized nutrition	Individualized nutrition Optimized nutrition

Primary Outcome Measures

Name	Time	Method
Linear Growth Velocity	36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first)	Increase in body length per week from birth to 36 weeks postmenstrual age or discharge
Growth Velocity	36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first)	Rate of weight gain \[g x kg-1 x day-1\] and length velocity \[cm x week-1\]

Secondary Outcome Measures

Name	Time	Method
Hypertension or High Systolic Blood Pressure	at 33-48 months adjusted age	Systolic blood pressure \>90th centile defined by the SUBCOMMITTEE ON SCREENING AND MANAGEMENT OF HIGH BLOOD PRESSURE IN CHILDREN
Rate of Weight Gain	36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first)	Rate of weight gain
Disproportionate Growth (Increased Fat Mass): BMI >90th Centile	36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first)	Disproportionate growth (increased fat mass): BMI \> 90th centile for sex and age
Leptin	33-48 months adjusted age	Serum levels of leptin (measure of adiposity)
Renal Function	33-48 months adjusted age	Serum level of cystatin C. This value increases if renal glomerular filtration decreases.
Comparison of Weight With Expected Value for Age and Gender	36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first)	Comparison of weight with expected value for age and gender: Z score for weight Expected mean for age and gender is zero. Normal is -2 to +2. Best is zero with concomitant zero for length.
Comparison of Length With Expected Value for Age and Gender	36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first)	Comparison of length with expected value for age and gender: Z score for length Expected mean for age and gender is zero. Normal is -2 to +2. Best is zero with concomitant zero for weight.
Rate of Linear Growth	36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first)	Rate of linear growth
Comparison of Rate of Head Growth With Expected Value for Age and Gender	36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first)	Change in z score for fronto-occipital circumference from birth to endpoint Expected mean for age and gender is zero. Normal is -2 to +2.
Blood Pressure	36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first)	Systolic blood pressure (calm or sleeping)
Body Composition	at 1 year of age and 3 years of age	Percent fat mass measured by Dexascan
Neurodevelopment	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	Bayley Scale of Infant and Toddler Development, Third Edition (BSID-III): language composite score Higher scores mean a better outcome. The composite scaled score has a mean of 100 and a SD of 15, a floor of 47 and a ceiling of 153.; Bayley, N. (2006). Bayley Scales of Infant and Toddler Development- Third Edition. San Antonio, TX: Harcourt Assessment.; DOI: 10.1177/0734282906297199
Comparison of Head Size With Expected Value for Age and Gender	36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first)	Comparison of head size with expected value for age and gender: Z score for fronto-occipital circumference Expected mean for age and gender is zero. Normal is -2 to +2. Best is zero.

Trial Locations

Locations (1)

UT Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States