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| Name | Class |
|---|---|
| Children's Medical Center Dallas | OTHER |
| The Gerber Foundation | OTHER |
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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.
Hypotheses:
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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Individualized and Optimized Nutrition | Experimental | Individualized nutrition Optimized nutrition |
|
| Optimized Nutrition | Other | Optimized nutrition |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Individualized Nutrition | Dietary Supplement | 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). |
| 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) |
| 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 |
| 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 |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Luc P Brion, MD | University of Texas Southwestern Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UT Southwestern Medical Center | Dallas | Texas | 75390-9063 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32071367 | Background | 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. | |
| 37964083 | Derived |
| Label | URL |
|---|---|
| DOI | View source |
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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.
after completion and publication of all follow-up data
on reasonable request
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Neonates were excluded if they received comfort care only, had a major congenital abnormality, or were too unstable for the first 7 days to have an accurate length measurement using a length board or a caliper.
Preterm neonates born at Parkland Hospital between January 27, 2016 and September 10, 2018
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| ID | Title | Description |
|---|---|---|
| FG000 | Individualized and Optimized Nutrition | Individualized nutrition Optimized nutrition 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). 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). |
| FG001 | Optimized Nutrition | Optimized nutrition 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). |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Individualized and Optimized Nutrition | Both individualized and optimized nutrition |
| BG001 | Optimized Nutrition | Optimized nutrition only |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Growth Velocity | Rate of weight gain [g x kg-1 x day-1] and length velocity [cm x week-1] | Posted | Mean | Standard Deviation | g kg-1 day-1 | 36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first) |
|
from birth to discharge from the neonatal intensive care unit
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Experimental | Optimized and individualized nutrition | 3 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Necrotizing enterocolitis | Gastrointestinal disorders | Systematic Assessment | Necrotizing enterocolitis stage II or greater (modified Bell's classification) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Feeding intolerance | Gastrointestinal disorders | Systematic Assessment | Feeding intolerance (feeds held for 24 h for abdominal distention, vomiting or residuals) |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| National Grant Gerber Foundation) (LPB); George L. MacGregor Professorship (CRR); National Children' | Gerber Foundation, UT Southwestern Med Ctr, Children's Medical Center | 214-648-3903 | luc.brion@utsouthwestern.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 11, 2020 | Apr 2, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D007235 | Infant, Premature, Diseases |
| ID | Term |
|---|---|
| D007232 | Infant, Newborn, Diseases |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
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Only the statistician and the formula technicians know the patients' allocation.
|
|
| Optimized nutrition | Dietary Supplement | 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). |
|
|
Systolic blood pressure (calm or sleeping)
| 36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first) |
| 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 |
| 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 |
| 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) |
| Body Composition | Percent fat mass measured by Dexascan | at 1 year of age and 3 years of age |
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) |
| Reis JD, Heyne R, Rosenfeld CR, Caraig M, Brown LS, Burchfield PJ, Lair CS, Petrosyan E, Jabob T, Nelson DB, Brion LP. Follow-up of a randomized trial optimizing neonatal nutrition in preterm very low birthweight infants: growth, serum adipokines, renal function and blood pressure. J Perinatol. 2024 Jan;44(1):78-86. doi: 10.1038/s41372-023-01821-2. Epub 2023 Nov 14. |
| 36473929 | Derived | Reis JD, Tolentino-Plata K, Caraig M, Heyne R, Rosenfeld CR, Brown LS, Brion LP. Double-blinded randomized controlled trial of optimizing nutrition in preterm very low birth weight infants: Bayley scores at 18-38 months of age. J Perinatol. 2023 Jan;43(1):81-85. doi: 10.1038/s41372-022-01572-6. Epub 2022 Dec 6. |
| BG002 | Total | Total of all reporting groups |
| weeks |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Birth weight | Mean | Standard Deviation | grams |
|
| Birth length | Accurate validated birth length was not obtained in 4 newborns. | Mean | Standard Deviation | cm |
|
| Birth fronto-occipital circumference | Mean | Standard Deviation | cm |
|
| OG001 | Optimized Nutrition | Optimized nutrition 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). |
|
|
| Primary | Linear Growth Velocity | Increase in body length per week from birth to 36 weeks postmenstrual age or discharge | Data were not available for patients transferred to another institution | Posted | Mean | Standard Deviation | cm per week | 36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first) |
|
|
|
| Secondary | Disproportionate Growth (Increased Fat Mass): BMI >90th Centile | Disproportionate growth (increased fat mass): BMI > 90th centile for sex and age | Total number is limited by need for accurate validated length and weight on the same day. This was not available in patients who were transferred. | Posted | Count of Participants | Participants | 36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first) |
|
|
|
| Secondary | Blood Pressure | Systolic blood pressure (calm or sleeping) | Posted | Mean | Standard Deviation | mm Hg | 36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first) |
|
|
|
| Secondary | 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 | 33-48 months adjusted age Not all participants entered follow-up and had data collected. | Posted | Count of Participants | Participants | at 33-48 months adjusted age |
|
|
|
| Secondary | 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 | BSID-III assessment was performed at 18-38 months of age corrected for prematurity, scored for corrected age, and adjusted for age of administration | Posted | Median | Inter-Quartile Range | score on a scale | 18-41 months adjusted age (postnatal age corrected for prematurity) |
|
|
|
| Secondary | 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 | BSID-III assessment was performed at 18-38 months of age corrected for prematurity, scored for corrected age, and adjusted for age of administration. | Posted | Median | Inter-Quartile Range | score on a scale | 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 |
|
|
|
| Secondary | Leptin | Serum levels of leptin (measure of adiposity) | 33-48 months adjusted age Not all participants entered follow-up and had data collected. | Posted | Mean | Standard Error | ng/ml | 33-48 months adjusted age |
|
|
|
| Secondary | Renal Function | Serum level of cystatin C. This value increases if renal glomerular filtration decreases. | 33-48 months adjusted age Not all participants entered follow-up and had data collected. | Posted | Mean | Standard Deviation | mg/dl | 33-48 months adjusted age |
|
|
|
| Secondary | 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. | Not all participants entered follow-up and had data collected. | Posted | Mean | Standard Deviation | Z-score | 36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first) |
|
|
|
| Secondary | 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. | Not all participants entered follow-up and had data collected. | Posted | Mean | Standard Deviation | Z-score | 36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first) |
|
|
|
| Secondary | 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. | Not all participants entered follow-up and had data collected. | Posted | Mean | Standard Deviation | Z-score | 36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first) |
|
|
|
| Secondary | Rate of Weight Gain | Rate of weight gain | Not all participants entered follow-up and had data collected. | Posted | Mean | Standard Deviation | g/kg/day | 36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first) |
|
|
|
| Secondary | Rate of Linear Growth | Rate of linear growth | Posted | Mean | Standard Deviation | cm/week | 36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first) |
|
|
|
| Secondary | 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. | Not all participants entered follow-up and had data collected. | Posted | Mean | Standard Deviation | Z-score | 36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first) |
|
|
|
| Secondary | Body Composition | Percent fat mass measured by Dexascan | Not Posted | at 1 year of age and 3 years of age | Participants |
| Other Pre-specified | 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) | Posted | Count of Participants | Participants | 36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first) |
|
|
|
| Other Pre-specified | 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 | Until 36 weeks postmenstrual age or discharge from the neonatal intensive care unit if earlier than 36 weeks | Posted | Count of Participants | Participants | 36 (range 35-37) weeks postmenstrual age or discharge (whichever comes first) |
|
|
|
| 62 |
| 6 |
| 62 |
| 19 |
| 62 |
| EG001 | Control | Optimized nutrition | 4 | 58 | 5 | 58 | 17 | 58 |
|
|
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| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|