Early Human Milk Fortification After Early, Exclusive, Enteral Nutrition in Very Preterm Infants

Study Overview
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Brief Summary
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In this proposed clinical trial, the investigators will randomize 80 very preterm (VPT) infants to receive either early (between day 4 and 7) or delayed (between day 10 and 14) fortification and determine if providing early protein supplementation through early fortification results in higher FFM-for-age z scores and more diversity in the gut microbiome.

Official Title
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Early Human Milk Fortification After Early, Exclusive, Enteral Nutrition in Very Preterm Infants: a Randomized Clinical Trial

Conditions
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Enteral Feeding Intolerance, Prematurity, Light-For-Dates

Intervention / Treatment
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* Dietary Supplement: Early HMF
* Dietary Supplement: Delayed HMF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Gestational age 29 to 33 weeks of gestation Birth weight < 1800 g Postnatal age < 96 hours Exclusion Criteria: Small for gestational age (<5th percentile) Major congenital/chromosomal anomalies Terminal illness needing withhold or limit 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early human milk fortification (HMF) group<br>A human milk fortifier will be added to the feeds between days 4 to 7, after a total feeding volume greater than 120 ml/kg/day is achieved. | Dietary Supplement: Early HMF<br>* Mom's milk or donor milk will be fortified between postnatal day 4 and 7<br>|
| Active Comparator: Delayed human milk fortification (HMF) group<br>A human milk fortifier will be added to the feeds between days 10 to 14, after a total feeding volume greater than 120 ml/kg/day is achieved. | Dietary Supplement: Delayed HMF<br>* Mom's milk or donor milk will be fortified between postnatal day 10 and 14<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 | Estimated by air displacement plethysmography | Postnatal day 14 to 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fecal microbiome composition | Determined by 16S RNA sequencing of bacteria in stool samples | Birth to 36 weeks postmenstrual age | 
| Growth - Weight | Measured weekly in grams and z scores as part of routine care | Birth to 36 weeks postmenstrual age or hospital discharge | 
| Growth - Length | Measured weekly in cm and z scores as part of routine care | Birth to 36 weeks postmenstrual age or hospital discharge | 
| Growth - Head circumference | Measured weekly in cm and z scores as part of routine care | 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 faltering | Diagnosis of growth faltering (decline in weight-for-age z score from birth to 36 weeks postmenstrual age greater than 1.2 | Birth to 36 weeks postmenstrual age or hospital discharge | 
| Number of participants with diagnosis of necrotizing enterocolitis | Diagnosis of necrotizing enterocolitis stage 2 or 3 | Birth to 60 days or discharge | 
| Number of participants with diagnosis of intestinal perforation | Diagnosis of intestinal perforation | Birth to 10 days | 
| Death | Death prior to postnatal day 60 | Birth to 60 days | 
| Duration of hospital stay in days | From day of admission to day of hospital discharge to home | Birth to 60 days or discharge, whichever occurs first |