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Targeted Fortification of Donor Breast Milk in Preterm Infants

Primary Purpose

Prematurity; Extreme, Failure to Thrive in Newborn, Growth Retardation

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Similac Human Milk Fortifier Extensively Hydrolyzed Protein Concentrated Liquid
Similac Liquid Protein Fortifier
Nestle Microlipid
Medica Nutrition SolCarb
Similac Human Milk Fortifier Extensively Hydrolyzed Protein Concentrated Liquid (Targeted Fortification)
Similac Liquid Protein Fortifier (Targeted Fortification)
Nestle Microlipid (Targeted Fortification)
Medica Nutrition SolCarb (Targeted Fortification)
Analysis with Miris (AB) Human Milk Analyzer
Sponsored by
Columbia University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Prematurity; Extreme focused on measuring Human Milk Analyzer, Miris, Target Fortification, Targeted Fortification, Donor Breast Milk

Eligibility Criteria

1 Day - 21 Days (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Premature infants born </= 30 weeks gestational age
  • Birth Weight </= 1500 grams

Exclusion Criteria:

  • Parents do no consent to donor milk
  • Confounders for poor growth such as congenital heart disease, GI diagnoses such as gastroschisis and omphalocele, and or major congenital anomalies
  • Grade III or IV intraventricular hemorrhage diagnoses prior to randomization
  • Small for gestational age (<3% on Fenton Growth Curve)
  • Failure to initiate fortified feeds prior to 3 weeks of life
  • Diagnosis of necrotizing entercolitis prior to randomization
  • Diagnosis of early onset sepsis confirmed with positive culture

Sites / Locations

  • Columbia University Medical Center/ New York - PresbyterianRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Experimental

Arm Label

Control

Experimental

Arm Description

Standard fortification of breast milk

Targeted fortification of breast milk

Outcomes

Primary Outcome Measures

Change in weight
Weight change in g/kg/day, z-score value, and change in z-score from week-to-week
Change in length
Length change in cm/kg/day, z-score value, and change in z-score from week-to-week
Head circumference
Head circumference change in cm/kg/day, z-score value, and change in z-score from week-to-week

Secondary Outcome Measures

Total Number of Days of Length of Stay in NICU
Today number of days in the NICU.
Rate of Mortality
Rate of morality during NICU hospitalization.
Number of Feeding Intolerance Events
The number of feeding intolerance events, defined as 1 or more feeds held.
Number of Necrotizing Enterocolitis Events
Number of necrotizing enterocolotis events.
Incidence of Bronchopulmonary dysplasia
Incidence of supplemental oxygen requirement at 36 weeks corrected gestational age.
Incidence of Retinopathy of prematurity
Incidence of retinopathy of prematurity
Percentage of Feeds with Donor Milk and Mother's Milk
Percent of feeds that are donor milk and mom's own milk.

Full Information

First Posted
March 2, 2020
Last Updated
September 16, 2022
Sponsor
Columbia University
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1. Study Identification

Unique Protocol Identification Number
NCT04294368
Brief Title
Targeted Fortification of Donor Breast Milk in Preterm Infants
Official Title
Targeted Fortification of Donor Breast Milk in Preterm Infants
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Recruiting
Study Start Date
March 9, 2020 (Actual)
Primary Completion Date
May 2023 (Anticipated)
Study Completion Date
July 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Columbia University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This study is a randomized controlled trial comparing standard fortification of donor breast milk to targeted fortification of donor breast milk in preterm infants. The purpose of the study is to determine if there is a benefit to target fortifying donor breast milk in the preterm population. The investigators hypothesize that infants receiving targeted fortification of donor breast milk will have improved growth compared to infants receiving standard fortification of donor breast milk.
Detailed Description
Breast milk is the best food for premature infants due to its ability to protect infants from necrotizing enterocolitis (NEC) and late onset sepsis. When a premature infant's mother's own milk supply is not enough to provide all the milk that her premature infant needs, donated breast milk is the next best option. One of the downsides of donor breast milk is that it often does not contain as much nutrition for the developing infant compared to the milk of a mother of a premature infant. This means a higher likelihood for poor growth in infant receiving mostly donor breast milk compared to mom's own milk. Due to an inability to easily measure the nutritional content of donor breast milk, standard practice has been to assume that the milk has a certain amount of fat, carbohydrates, and protein. Based on these assumptions, a set amount of additional nutritional fortifier is added to both donor and mom's own breast milk prior to it being given to the infant. Studies show that there is often less nutrition in the donor breast milk to start with than assumed. Technology is now available which uses a small volume sample to measure fat, protein, and carbohydrates in human milk, and hence, calculate the calories in the milk. Using this technology, in this study, the investigators will customize the fortification of donor breast milk by first measuring what is in the milk and then adding any additional fortification that is needed to reach the recommended goals for fat, protein, and carbohydrates. The investigators hypothesize that infants receiving this customized milk, so-called "target" fortified donor breast milk, will have better growth than infants receiving the standard amount of fortification added to their donor breast milk. The study design involves measurement of macronutrient and calorie content of donor breast milk using a point-of-care human milk analyzer (Miris, AB). The individual macronutrient (protein, fat, and carbohydrate) concentrations will be targeted in the intervention group such that the infant will receive protein of 4 g/kg/day, fat of 6.6 g/kg/day, and carbohydrates of 11.6-13.2 g/kg/day. Fortification will be added in a step-wise fashion daily over a 3-4 day period starting when the infant reaches about 80 ml/kg/day in feeding volume. Fortifiers that may be used in this study include: Abbott Similac Human Milk Fortifier Extensively Hydrolyzed Protein Concentrated Liquid, Abbott Liquid Protein, Nestle Microlipid, and Medica Nutrition SolCarb. Participants in the control arm will receive donor milk that is fortified in the standard fashion at this institution; that is, 4 packets of Human Milk Fortifier will be added to 100 ml of donor breast milk. Additional fortification such as liquid protein or microlipid may be added to the donor milk and mom's own milk in response to poor growth for participants in both groups, as is standard of care in this Neonatal Intensive Care Unit (NICU). Patients in both experimental and control groups will always receive mom's own milk first when it is available. Mom's own milk will not be analyzed and will always be fortified in the standard fashion for both groups. The participants will be studied until they reach 34 weeks corrected gestational age.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prematurity; Extreme, Failure to Thrive in Newborn, Growth Retardation, Growth Failure, Infant Nutrition Disorders
Keywords
Human Milk Analyzer, Miris, Target Fortification, Targeted Fortification, Donor Breast Milk

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Control group to receive standard fortification of donor breast milk. Experimental group to receive targeted fortification of donor breast milk.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Control
Arm Type
Other
Arm Description
Standard fortification of breast milk
Arm Title
Experimental
Arm Type
Experimental
Arm Description
Targeted fortification of breast milk
Intervention Type
Dietary Supplement
Intervention Name(s)
Similac Human Milk Fortifier Extensively Hydrolyzed Protein Concentrated Liquid
Intervention Description
The control group will receive mother's breast milk when it is available. Mother's breast milk will be fortified with 4 packets of Similac Human Milk Fortifier (HMF) per 100 mL. When mother's breast milk is not available, participants will be fed donor breast milk with 4 packets of HMF.
Intervention Type
Dietary Supplement
Intervention Name(s)
Similac Liquid Protein Fortifier
Intervention Description
For participants in the control group, additional fortification can be added to the milk for patients in this group in response to poor growth, as is standard of care in the NICU. The standard dose is 1 ml per 30 ml of breast milk.
Intervention Type
Dietary Supplement
Intervention Name(s)
Nestle Microlipid
Intervention Description
For participants in the control group, additional fortification can be added to the milk for patients in this group in response to poor growth, as is standard of care in the NICU. The standard dose is 1 ml per 30 ml of breast milk.
Intervention Type
Dietary Supplement
Intervention Name(s)
Medica Nutrition SolCarb
Intervention Description
For participants in the control group, additional fortification can be added to the milk for patients in this group in response to poor growth, as is standard of care in the NICU.
Intervention Type
Dietary Supplement
Intervention Name(s)
Similac Human Milk Fortifier Extensively Hydrolyzed Protein Concentrated Liquid (Targeted Fortification)
Intervention Description
The experimental group will receive mother's breast milk when it is available. Mother's breast milk will be fortified with 4 packets of Similac Human Milk Fortifier (HMF) per 100 mL. When mother's breast milk is not available, participants will be fed donor breast milk with 4 packets of HMF. For participants in the experimental group, the investigators will continue to add fortification. Two packets of HMF per day will be added until goal fortification is reached.
Intervention Type
Dietary Supplement
Intervention Name(s)
Similac Liquid Protein Fortifier (Targeted Fortification)
Intervention Description
Participants in the experimental group will receive a dose that will vary depending on the base protein content in the donor breast milk for each particular batch of donor breast milk.
Intervention Type
Dietary Supplement
Intervention Name(s)
Nestle Microlipid (Targeted Fortification)
Intervention Description
Participants in the experimental group will receive a dose that will vary depending on the base fat content in the donor breast milk for each particular batch of donor breast milk
Intervention Type
Dietary Supplement
Intervention Name(s)
Medica Nutrition SolCarb (Targeted Fortification)
Intervention Description
Participants in the experimental group will receive a dose that will vary depending on the base carbohydrate content in the donor breast milk for each particular batch of donor breast milk
Intervention Type
Other
Intervention Name(s)
Analysis with Miris (AB) Human Milk Analyzer
Intervention Description
For participants in both the control and the experimental arms, each batch of donor milk will be analyzed using the Miris Human Milk Analyzer. Manufacturer recommendations for milk analysis will be strictly followed.
Primary Outcome Measure Information:
Title
Change in weight
Description
Weight change in g/kg/day, z-score value, and change in z-score from week-to-week
Time Frame
Up to 11 weeks
Title
Change in length
Description
Length change in cm/kg/day, z-score value, and change in z-score from week-to-week
Time Frame
Up to 11 weeks
Title
Head circumference
Description
Head circumference change in cm/kg/day, z-score value, and change in z-score from week-to-week
Time Frame
Up to 11 weeks
Secondary Outcome Measure Information:
Title
Total Number of Days of Length of Stay in NICU
Description
Today number of days in the NICU.
Time Frame
Up to 1 year
Title
Rate of Mortality
Description
Rate of morality during NICU hospitalization.
Time Frame
Up to one year
Title
Number of Feeding Intolerance Events
Description
The number of feeding intolerance events, defined as 1 or more feeds held.
Time Frame
Up to 34 weeks corrected gestational age
Title
Number of Necrotizing Enterocolitis Events
Description
Number of necrotizing enterocolotis events.
Time Frame
Up to 1 year of age
Title
Incidence of Bronchopulmonary dysplasia
Description
Incidence of supplemental oxygen requirement at 36 weeks corrected gestational age.
Time Frame
Up to 1 year of age
Title
Incidence of Retinopathy of prematurity
Description
Incidence of retinopathy of prematurity
Time Frame
Up to 1 year of age
Title
Percentage of Feeds with Donor Milk and Mother's Milk
Description
Percent of feeds that are donor milk and mom's own milk.
Time Frame
Up to 34 weeks corrected gestational age

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Day
Maximum Age & Unit of Time
21 Days
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Premature infants born </= 30 weeks gestational age Birth Weight </= 1500 grams Exclusion Criteria: Parents do no consent to donor milk Confounders for poor growth such as congenital heart disease, GI diagnoses such as gastroschisis and omphalocele, and or major congenital anomalies Grade III or IV intraventricular hemorrhage diagnoses prior to randomization Small for gestational age (<3% on Fenton Growth Curve) Failure to initiate fortified feeds prior to 3 weeks of life Diagnosis of necrotizing entercolitis prior to randomization Diagnosis of early onset sepsis confirmed with positive culture
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jenny Taylor, MD
Phone
212-305-8500
Email
jt3073@cumc.columbia.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marianne Garland, MD
Organizational Affiliation
Columbia University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Columbia University Medical Center/ New York - Presbyterian
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jenny Taylor, MD
Phone
212-305-8500
Email
jt3073@cumc.columbia.edu
First Name & Middle Initial & Last Name & Degree
Marianne Garland, MD

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Individual participant data (IPD) may be shared with other researchers at Columbia University Medical Center at the end of the study for the purposes of creating a neurodevelopmental follow-up study that involves following participants in the study until they reach 2 years (corrected post-natal age) in neurodevelopment follow-up clinic. Permission for future contact is included in the consent form for participants in this study. Only participants who consent to future contact will be approached about a neurodevelopmental follow-up study.
Citations:
PubMed Identifier
30968003
Citation
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Results Reference
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26037506
Citation
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Results Reference
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Citation
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Citation
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Targeted Fortification of Donor Breast Milk in Preterm Infants

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