Exclusive Human Milk Feeding in Infants With Single Ventricle Physiology

A Randomized Controlled Trial to Evaluate Growth Velocity and Clinical Outcomes of Infants With Single Ventricle Physiology Fed an Exclusive Human Milk Diet With Early Nutritional Fortification Following Surgical Repair

A randomized, blinded, controlled trial to evaluate growth velocity and clinical outcomes in infants with single ventricle physiology fed an exclusive human milk diet prior to, and throughout the post-operative period following, surgical repair. Human milk is defined as expressed human milk or donor milk and its derivatives, human milk-based fortifier and human milk caloric fortifier.

The study hypothesis is that infants fed an exclusive human milk diet will have short and long term benefits, with improved wound healing, growth, and neurodevelopmental outcomes while reducing episodes of feeding intolerance and necrotizing enterocolitis (NEC).

Study Overview

• Status: Completed
• Conditions: Congenital Heart Defect
• Intervention / Treatment: Other: Human Milk Derived Fortifier; Other: Human/Bovine Milk

Detailed Description

This is a single blinded (physician investigator), randomized, controlled trial to evaluate growth velocity and clinical outcomes in infants with single ventricle physiology fed an exclusive human milk diet during their initial hospitalization after birth and through the 30 days post-surgical repair feeding period or hospital discharge, whichever comes first.

Subjects will be randomized to one of two groups at birth or immediately following diagnosis if prenatal care was not obtained prior to birth. Parents who decline participation by their infants in the study will be asked to consent to data gathering on their infants who will be treated and fed per institutional practice. The data on these individuals will be summarized and evaluated descriptively in comparison with the actual trial results.

All patients will receive exclusive maternal human milk or donor human milk prior to randomization. Once randomized, patients in Group One will receive an exclusive human milk diet prior to the surgery and throughout the 30-day feeding period following surgical repair or until hospital discharge, whichever comes first. Day 1 is defined as the day of the first enteral feed post-surgery. Patients in Group Two (Control Group) will receive maternal human milk or formula or donor human milk (per standard of care at each hospital) in the pre-surgical period. In the post-surgical period the control group will receive human milk or formula, as per feeding algorithm The primary objective of this study is to evaluate growth velocity (weight velocity [g/kg/day] and weight z-score from World Health Organization (WHO) growth charts) at 30 days after the initiation of feed post-surgery for infants with single ventricle physiology who are fed an exclusive human milk diet from birth through the 30 day feeding period following surgical repair or until hospital discharge, whichever comes first.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Loma Linda, California, United States, 92354
      • Loma Linda University
    • Los Angeles, California, United States, 90027
      • Los Angeles Children's Hospital
    • Orange, California, United States, 92868
      • Children's Hospital Orange County
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida Children's Hospital
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Lurie Children's Hospital
  • New York
    • New York, New York, United States, 10027
      • Columbia University
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinatti Children's Hospital Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • OU Children's Hospital at OU Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Medical
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital
    • San Antonio, Texas, United States, 78229
      • University Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 1 week (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Term infants (≥37 and 0/7 weeks gestational age) ≤ 7 days old with a diagnosis of single ventricle physiology who are thought to require a single ventricle repair at the time of enrollment.
2. Infant feeding was NPO or consisted of 100% human milk diet prior to enrollment
3. Parent(s) willing to sign informed consent.
4. Parent(s) willing to comply with study follow-up procedures.
5. Require surgical palliation within the first 1 month of life.

Exclusion Criteria:

1. Term infants >7 days old at the time of diagnosis.
2. <37 weeks gestation
3. Infants requiring cardio-pulmonary resuscitation prior to surgical repair.
4. Outborn infants who received enteral nutrition at the other institution prior to surgical repair. If it is uncertain if infant received even 1 bottle or a small amount of formula, infants will be excluded.

5. Major congenital abnormalities that could significantly affect survival such as:

   1. Confirmed or suspected major genetic abnormalities (lethal or with extremely low probability for survival).
   2. Chromosomal abnormalities: Trisomies (13, 18, 21 etc.) deletions or translocations (Turner/Williams Syndrome, DiGeorge, to name a few)
   3. Major organ system abnormalities not related to a genetic syndrome that are lethal or have extremely low probability for survival (i.e, bilateral kidney intrinsic disease, pulmonary hypoplasia, Central Nervous System (CNS) malformations: Arnold Chiari, myelomeningoceles, hydranencephaly, schizencephaly, holoprosencephaly))
   4. Heterotaxia
   5. Metabolic disorders affecting growth: homocystinuria, methylmalonic acidemias, propionic acidemias, urea cycle defects
6. Evidence of intracerebral hemorrhage (IVH) ≥ Grade 3
7. Any comorbidity or significant clinical event prior to enrollment, deemed by the Investigator as likely to affect survival.
8. Requires Extracorporeal Membrane Oxygenation (ECMO) pre-operatively
9. Legally Authorized Representative(s) unwilling to comply with an exclusive human milk diet either in the form of mother's milk, human milk-based human milk fortifier, human milk based caloric fortifier or donor human milk during the initial hospitalization period and through the 30 day feeding period after surgical repair or hospital discharge, whichever comes first.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exclusive Human Milk; All infants randomized to this arm will receive exclusive human milk diet with addition of human milk derived fortifier from birth to 30 days post initiation of feedings after initial palliative cardiac surgery	Other: Human Milk Derived Fortifier; Human milk derived fortifier will be utilized to increase caloric intake in infants assigned to the exclusive human milk arm
Active Comparator: Human/Bovine Milk; All infants randomized to this arm will receive exclusive human milk diet prior to randomization and will use either human and/or bovine milk and fortifier per the institution's standard practice 30 days post initiation of feedings after initial palliative cardiac surgery	Other: Human/Bovine Milk; Bovine milk derived fortification; Other Names: Human/Formula Milk

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
growth velocity	weight velocity in g/kg/day	30 days
growth velocity	weight z-score 30 days post 1st operation	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
linear growth rate	cm/week	6 months
linear growth rate	z-score	6 months
head circumference growth rate	cm/week	6 months
head circumference growth rate	z-score	6 months
Feeding Intolerance	defined as nil per os (NPO) for at least 24 in the 30 days of post-surgery enteral feeding period (day 1 is the first day of feeding post-op), NPO due to elective surgeries or procedures will not be defined as feeding intolerance.	30 days
Length of stay	time hospitalized after 1st surgery	up to 24 months
Sepsis	Sepsis 30 days post 1st operation	30 days
Necrotizing enterocolitis	NEC 30 days post 1st operation	30 days
wound infections	wound infection 30 days post 1st operation	30 days
wound dehiscence	wound dehiscence 30 days post 1st operation	30 days
parenteral nutrition	in days, during the 30 day post 1st operation	30 days

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center at San Antonio
• Collaborators: Baylor College of Medicine; Columbia University; University of Oklahoma; University of Florida; Ann & Robert H Lurie Children's Hospital of Chicago; Children's Hospital Medical Center, Cincinnati; University of Texas; Children's Hospital of Orange County; Prolacta Bioscience; Cook Children's Medical Center
• Investigators: Principal Investigator: Cynthia Blanco, MD, The University of Texas Health Science Center at San Antonio

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2016
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): October 6, 2022

Study Registration Dates

• First Submitted: July 28, 2016
• First Submitted That Met QC Criteria: August 4, 2016
• First Posted (Estimated): August 9, 2016

Study Record Updates

• Last Update Posted (Actual): September 26, 2023
• Last Update Submitted That Met QC Criteria: September 25, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Single Ventricle; Congenital Heart Defect
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Defects, Congenital; Univentricular Heart
• Other Study ID Numbers: HSC20150779H

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: It is a blinded study