Exclusive Human Milk Feeding in Infants With Single Ventricle Physiology

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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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

Conditions
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Congenital Heart Defect

Intervention / Treatment
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* Other: Human Milk Derived Fortifier
* Other: Human/Bovine Milk


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Infant feeding was NPO or consisted of 100% human milk diet prior to enrollment Parent(s) willing to sign informed consent. Parent(s) willing to comply with study follow-up procedures. Require surgical palliation within the first 1 month of life. Exclusion Criteria: Term infants >7 days old at the time of diagnosis. <37 weeks gestation Infants requiring cardio-pulmonary resuscitation prior to surgical repair. 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. Major congenital abnormalities that could significantly affect survival such as: Confirmed or suspected major genetic abnormalities (lethal or with extremely low probability for survival). Chromosomal abnormalities: Trisomies (13, 18, 21 etc.) deletions or translocations (Turner/Williams Syndrome, DiGeorge, to name a few) 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)) Heterotaxia Metabolic disorders affecting growth: homocystinuria, methylmalonic acidemias, propionic acidemias, urea cycle defects Evidence of intracerebral hemorrhage (IVH) ≥ Grade 3 Any comorbidity or significant clinical event prior to enrollment, deemed by the Investigator as likely to affect survival. Requires Extracorporeal Membrane Oxygenation (ECMO) pre-operatively 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.

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 7 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exclusive Human Milk<br>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<br>* Human milk derived fortifier will be utilized to increase caloric intake in infants assigned to the exclusive human milk arm<br>|
| Active Comparator: Human/Bovine Milk<br>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<br>* Bovine milk derived fortification<br>* Other names: Human/Formula Milk;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Single Ventricle, Congenital Heart Defect