Optimizing Individual Nutrition in Preterm Very Low Birth Weight Infants

Individualizing and Optimizing Nutrition to Prevent Metabolic Syndrome and To Improve Neurodevelopment in Preterm and Small for Gestational Age Infants

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.

Study Overview

• Status: Completed
• Conditions: Infant, Premature, Diseases; Infant, Small for Gestational Age
• Intervention / Treatment: Dietary supplement: Individualized Nutrition; Dietary supplement: Optimized nutrition

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.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390-9063
      • UT Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 week (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Individualized and Optimized Nutrition; Individualized nutrition Optimized nutrition	Dietary supplement: Individualized Nutrition; Intake of macronutrients (protein, fat, and carbohydrate) will be individualized every day by adding one or more macronutrients to human milk based on daily measurements using near-infrared analysis. In patients receiving less milk than 140 ml x kg-1 x day-1 fortification of human milk will be adjusted to reach at least the average concentrations of protein, fat, and carbohydrate in donor's milk (Wojcik. J Am Diet Assoc. 2009 Jan;109:137-40) and 20 cal/oz as provided by the Mother's Milk Bank of North Texas. In those receiving at least 140 ml x kg-1 x day-1 of milk at 24 cal/oz fortification will be adjusted to meet recent guidelines from the the European Society of Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition (ESPGHAN) (Agostoni et al. J Pediatr Gastroenterol Nutr. 2010 Jan;50:85-91).; Other Names: Targeted, customized; Dietary supplement: 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 (corrected for serum creatinine level) and albumin and velocity of growth (weight and length).; Other Names: Adjustable
Other: Optimized Nutrition; Optimized nutrition	Dietary supplement: 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 (corrected for serum creatinine level) and albumin and velocity of growth (weight and length).; Other Names: Adjustable

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disproportionate Growth (Increased Fat Mass): BMI >90th Centile	Disproportionate growth (increased fat mass): BMI > 90th centile for sex and age	36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first)
Blood Pressure	Systolic blood pressure (calm or sleeping)	36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first)
Neurodevelopment	Bayley Scale of Infant and Toddler Development, Third Edition (BSID-III): cognitive 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 55 and a ceiling of 145. Bayley, N. (2006). Bayley Scales of Infant and Toddler Development- Third Edition. San Antonio, TX: Harcourt Assessment. DOI: 10.1177/0734282906297199	18-41 months adjusted age (postnatal age corrected for prematurity)
Neurodevelopment	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	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
Body Composition	Percent fat mass measured by Dexascan	at 1 year of age and 3 years of age
Hypertension or High Systolic Blood Pressure	Systolic blood pressure >90th centile defined by the SUBCOMMITTEE ON SCREENING AND MANAGEMENT OF HIGH BLOOD PRESSURE IN CHILDREN	at 33-48 months adjusted age
Leptin	Serum levels of leptin (measure of adiposity)	33-48 months adjusted age
Renal Function	Serum level of cystatin C. This value increases if renal glomerular filtration decreases.	33-48 months adjusted age
Comparison of Weight With Expected Value for Age and Gender	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.	36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first)
Comparison of Length With Expected Value for Age and Gender	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.	36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first)
Comparison of Head Size With Expected Value for Age and Gender	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.	36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first)
Rate of Weight Gain	Rate of weight gain	36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first)
Rate of Linear Growth	Rate of linear growth	36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first)
Comparison of Rate of Head Growth With Expected Value for Age and Gender	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.	36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	Percent of infants who died from birth to endpoint (36 weeks post menstrual age or discharge from the neonatal intensive care unit if earlier than 36 weeks)	36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first)
Necrotizing Enterocolitis	Percentage of infants who developed necrotizing enterocolitis stage II or greater (using the modified Bell stage classification) in the neonatal intensive care unit	36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first)

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: Children's Medical Center Dallas; The Gerber Foundation
• Investigators: Principal Investigator: Luc P Brion, MD, UT Southwestern Medical Center

Publications and helpful links

General Publications

• 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.

Helpful Links

• DOI

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Actual): December 31, 2023
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: February 12, 2015
• First Submitted That Met QC Criteria: February 19, 2015
• First Posted (Estimated): February 26, 2015

Study Record Updates

• Last Update Posted (Actual): July 3, 2024
• Last Update Submitted That Met QC Criteria: June 7, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infant, Newborn, Diseases; Infant, Premature, Diseases
• Other Study ID Numbers: STU 102014-056

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The datasets generated and/or analyzed during the current study will be available from the corresponding author on reasonable request after completion and publication of all follow-up data.
• IPD Sharing Time Frame: after completion and publication of all follow-up data
• IPD Sharing Access Criteria: on reasonable request
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF