Early Progressive Feeding in Human-Milk Fed Extremely Preterm Infants: A Randomized Trial

Study Overview
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Brief Summary
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To test the hypothesis that progressive feeding without minimal enteral feeding (MEF) compared to progressive feeding preceded by a 4-day course of MEF will result in an increased number of days alive on full enteral feeding in the first 28 days after birth in extremely preterm infants receiving human milk.

Detailed Description
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Qualifying participants will be randomly assigned to one of two study groups: 1) Early progressive feeding without MEF or 2) Progressive feedings preceded by 4 days of MEF. Regardless of study group assignment, donor human milk will be offered if not enough of the mother's expressed breastmilk during the intervention phase of the trial. Intervention group: Progressive feeding of 20-24 ml/kg/d on day 1 of feeding, followed by daily increments of 24-25 ml/kg/d as tolerated until full enteral feeding achieved. Control group: MEF with feeding volumes of 20-24 ml/kg/d for 4 days followed by progressive feeding (daily increments of 24-25 ml/kg/d) as tolerated until full enteral feeding achieved. Both groups will receive fast progressive feeding (>/= 24 ml/kg/day) If parent agrees, stool dirty diapers will be collected 5 times (at birth, 1, 2, 3 and 4 weeks of life).

Official Title
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Early Progressive Feeding in Human-Milk Fed Extremely Preterm Infants: A Randomized Trial

Conditions
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Premature; Infant, Light-for-dates

Intervention / Treatment
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* Other: Progressive Feeding without MEF
* Other: Progressive Feeding with MEF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: admission to the NICU within 48 hours with gestational age between 22.0 and 28.6 weeks Exclusion Criteria: small for gestational age (<10th percentile birthweight), major congenital or chromosomal anomalies, and infants with terminal illness in which decision to withhold or limit support have been made

Ages Eligible for Study
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Minimum Age: 24 Hours
Maximum Age: 48 Hours

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Progressive Feeding without MEF<br>This group will receive feeding volumes of 20-24ml/kg/d of day 1 of feeding followed by the study intervention of daily volume increases in increments of 24-25ml/kg/d as tolerated until full enteral feeding is achieved. | Other: Progressive Feeding without MEF<br>* This group will receive feeding volumes of 20-24ml/kg/d of day 1 of feeding followed by the study intervention of daily volume increases in increments of 24-25ml/kg/d as tolerated until full enteral feeding is achieved.<br>|
| Active Comparator: Progressive Feeding with MEF<br>This group will receive minimal enteral feeds (MEF) with volumes of 20-24ml/kg/d for 4 days followed by daily increases in increments of 24-25ml/kg/d as tolerated until full enteral feeding is achieved. | Other: Progressive Feeding with MEF<br>* This group will receive minimal enteral feeds (MEF) with volumes of 20-24ml/kg/d for 4 days followed by daily increases in increments of 24-25ml/kg/d as tolerated until full enteral feeding is achieved.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of days alive and receiving full enteral feeding | number of days alive on full enteral feeding in the first 28 days after birth | birth to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  | birth to 14 days | 
| Death | death prior to 121 days of birth | birth to 120 days | 
| Number of days alive and receiving full enteral feeding according to time of exposure to human milk and formula feeding the first 28 days |  | birth to 28 days | 
| Time to establish full enteral feeding | time interval between birth and full enteral feeding at 120cc/kg/day | 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 | 
| Number of episodes of feeding intolerance resulting in an interruption or cessation of progressive enteral feeding for a period < 12 hours |  | birth to 28 days | 
| Number of days receiving parenteral nutrition |  | birth to 28 days | 
| Number of days requiring central line access |  | birth to 28 days | 
| Number of episodes of culture proven sepsis |  | birth to 120 days or discharge, whichever occurs first | 
| Growth/length at time of discharge |  | birth to 120 days or discharge, whichever occurs first | 
| Duration of hospital stay in days |  | birth to 120 days or discharge, whichever occurs first | 
| Changes in intestinal microbiome | Determined by molecular analyses of bacteria in fecal samples | birth to 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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premature infant, early progressive feeding