Early Protein Supplementation in Extremely Preterm Infants Fed Human Milk

Study Overview
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Brief Summary
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The central hypothesis of this clinical trial is that, in extremely preterm infants, protein-enriched human milk diets compared to usual human milk diets during the first 2 weeks after birth increase fat-free mass (FFM)-for-age Z scores and promote maturation of the gut microbiome at term corrected age.

Detailed Description
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Masked randomized clinical trial in which extremely preterm infants fed human milk will be randomly assigned to receive either a protein-enriched diet (intervention group) or a usual diet (control group) within the first 96 hours after birth.

Official Title
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Early Life Protein-enriched Human Milk Diets to Increase Lean Body Mass Accretion and Diversity of the Gut Microbiome in Extremely Preterm Infants: a Randomized Trial

Conditions
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Prematurity; Extreme, Feeding Disorder Neonatal, Breast Milk Expression, Growth Failure, Microbial Colonization

Intervention / Treatment
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* Procedure: Protein-enriched human milk diet
* Procedure: Usual human milk diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Gestational age ≤ 28 weeks of gestation Postnatal age < 96 hours Exclusion Criteria: Congenital malformations Chromosomal anomalies Terminal illness needing to limit or withhold support

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 4 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Protein-enriched human milk diet<br>Infants in this group will receive protein-enriched expressed human milk or donor human milk during the first 2 weeks after birth. | Procedure: Protein-enriched human milk diet<br>* 1.2 g of human-based protein will be added to each 100 ml of human milk administered<br>|
| Active Comparator: Usual human milk diet<br>Infants in this group will receive either expressed human milk or donor human milk during the first 2 weeks after birth. | Procedure: Usual human milk diet<br>* Human-based protein will not be added to the human milk administered.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fat-free mass(FFM)-for-age Z-score | FFM accretion will be estimated by air displacement plethysmography | 36 weeks or hospital discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fat mass(FM)-for-age Z-score | FM accretion will be estimated by air displacement plethysmography | 36 weeks or hospital discharge | 
| Body fat(BF)-for-age Z-score | Percent BF will be estimated by air displacement plethysmography | 36 weeks or hospital discharge | 
| Anthropometric measurements | Weight, length, and head circumference measurements at regular intervals | Birth to 36 weeks postmenstrual age or hospital discharge | 
| Growth rate | Weight gain in g/kg/day | Birth to 36 weeks postmenstrual age or hospital discharge | 
| Number of participants with postnatal growth failure | Diagnosis of growth failure (weight < 10th percentile) | 36 weeks or hospital discharge | 
| Number of participants with diagnosis of necrotizing enterocolitis | Diagnosis of necrotizing enterocolitis stage 2 or 3 | Birth to 120 days or discharge, whichever occurs first | 
| Number of participants with diagnosis of intestinal perforation | Diagnosis of intestinal perforation | Birth to 120 days or discharge, whichever occurs first | 
| Death | Death prior to 121 days of birth | Birth to 120 days | 
| Culture-proven sepsis | Diagnosis of sepsis with positive blood cultures | Birth to 120 days | 
| Number of days alive and receiving full enteral feeding | Total number of full enteral feeding days | Birth to 28 days | 
| Number of episodes of feeding intolerance | Interruption or cessation of enteral feeds for a period greater than 12 hours for abnormal abdominal examination | Birth to 28 days | 
| Duration of hospital stay in days | From day of admission to day of hospital discharge to home | Birth to 120 days or discharge, whichever occurs first | 
| Serum creatinine | Highest serum creatinine value in the first 28 days after birth | Birth to 28 days |