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Targeting Human Milk Fortification to Improve Preterm Infant Growth and Brain Development

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03977259
Recruitment Status : Not yet recruiting
First Posted : June 6, 2019
Last Update Posted : June 10, 2019
Sponsor:
Information provided by (Responsible Party):
Mandy Brown Belfort, MD MPH, Brigham and Women's Hospital

Brief Summary:
This study is a randomized trial comparing 2 methods of human milk fortification for preterm infants in the neonatal intensive care unit (NICU). All participating infants will receive a human milk diet comprising maternal and/or donor milk plus multi-component and modular fortifiers. In one group (control), the milk will be fortified according to routine standard of care. In the other group (intervention), the fortification will be individually targeted based on the results of point-of-care human milk analysis. Outcomes include physical growth in the NICU and after discharge, brain structure by magnetic resonance imaging at term equivalent age, and neurodevelopment at 2 years.

Condition or disease Intervention/treatment Phase
Preterm Birth Breast Milk Expression Nutrition Disorder, Infant Brain Development Abnormality Neurodevelopmental Disorders Other: Individually targeted fortification Not Applicable

Detailed Description:

Human milk is the recommended diet for preterm infants and it requires fortification to meet their high nutrient requirements. This study addresses a gap in knowledge about the optimal strategy for human milk fortification in the neonatal intensive care unit (NICU).

Infants will be recruited from a single site (Brigham and Women's Hospital, Boston MA). Eligible infants are NICU inpatients born <32 weeks' gestation and enrolled within 21 days of birth, whose mothers are providing breast milk. Exclusion criteria include major congenital anomalies, severe fetal growth restriction (weight <3rd percentile), clinically significant gastrointestinal pathology, triplets or higher order multiples, and expected death or transfer. Infants who require fluid restriction <140 mL/kg/day will also be excluded.

The study period begins when infants have reached full volume (150-160 mL/kg/day) human milk feedings fortified to 24 kcal per ounce. Participants will be randomized to one of two diet groups; twins will be randomized separately. The study diet will continue until 36 weeks' postmenstrual age or hospital discharge, whichever comes first.

Available maternal milk will be pooled with donor milk (if needed) to reach the total daily fluid volume; this "base" milk will be analyzed with a point-of-care human milk analyzer (Miris, AB). All infants will receive at minimum the standard human milk fortification (multicomponent fortifier to 24 kcal/oz plus liquid protein 0.27 g/dL). In one group (control), we will follow the standard of care for milk fortification, only adding more protein and/or energy if weight gain is lagging. In the other group (intervention), we will individually target fortification with additional protein and/or energy so that the "base" milk always contains protein 1 g/dL and energy 67 kcal/dL.

Outcome measures will include physical growth during the diet intervention period, including gain in weight, length, and head circumference and body composition with air displacement plethysmography at the end of the diet intervention. At term equivalent age, participants will undergo brain magnetic resonance imaging. At 2 years corrected age, outcomes include standard and novel neurodevelopmental tests including the Bayley-III and tests of emerging executive function; and physical size.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Parents, clinical, and research staff apart from the study milk technician will be unaware of the treatment group.
Primary Purpose: Supportive Care
Official Title: Targeting Human Milk Fortification to Improve Preterm Infant Growth and Brain Development
Estimated Study Start Date : September 2019
Estimated Primary Completion Date : June 2024
Estimated Study Completion Date : June 2024

Arm Intervention/treatment
No Intervention: Standard fortification
Standard of care fortification with multicomponent human milk fortifier (24 kcal/oz) and liquid protein (0.27 g/dL); additional protein and/or calories added only for growth faltering.
Experimental: Individually targeted fortification
Standard of care fortification plus extra protein and/or calories to ensure that "base" milk has protein 1 g/dL and calories 67/dL.
Other: Individually targeted fortification
Abbott liquid protein and/or medium chain triglyceride are added routinely to ensure that the "base" milk has protein 1 g/dL and calories 67/dL.




Primary Outcome Measures :
  1. Weight [ Time Frame: at study endpoint (36 weeks' postmenstrual age or discharge) ]
    Weight z-score

  2. Length [ Time Frame: at study endpoint (36 weeks' postmenstrual age or discharge) ]
    Length z-score

  3. Fat free mass [ Time Frame: at study endpoint (36 weeks' postmenstrual age or discharge) ]
    Fat free mass estimated with air displacement plethysmography (z-score)

  4. Total brain volume [ Time Frame: at term equivalent age (38 to 41 weeks' postmenstrual age) ]
    Total brain volume by MRI

  5. Cerebellar volume [ Time Frame: at term equivalent age (38 to 41 weeks' postmenstrual age) ]
    Cerebellar volume by MRI

  6. Bayley-III cognitive score [ Time Frame: at 2 years' corrected age ]
    Scaled composite score (continuous), higher score indicates better performance, range of possible scores 55-145

  7. Bayley-III motor score [ Time Frame: at 2 years' corrected age ]
    Scaled composite score (continuous), higher score indicates better performance, range of possible scores 46-154


Secondary Outcome Measures :
  1. Fat mass [ Time Frame: at study endpoint (36 weeks' postmenstrual age or discharge) ]
    Fat mass estimated with air displacement plethysmography (z-score)

  2. Weight [ Time Frame: at 2 years' corrected age ]
    Weight z-score

  3. Height [ Time Frame: at 2 years' corrected age ]
    Height z-score

  4. Low Bayley-III cognitive score [ Time Frame: At 2 years' corrected age ]
    Scaled composite score <85 (>1 standard deviation below the normative mean)

  5. Low Bayley-III motor score [ Time Frame: At 2 years' corrected age ]
    Scaled composite score <85 (>1 standard deviation below the normative mean)

  6. Bayley-III language score [ Time Frame: At 2 years' corrected age ]
    Scaled composite score (continuous), higher score indicates better performance, range of possible scores 46-154

  7. Bayley-III language score [ Time Frame: At 2 years' corrected age ]
    Scaled composite score <85 (>1 standard deviation below the normative mean)

  8. Spacial working memory [ Time Frame: at 2 years' corrected age ]
    Spin the Pots task (number of trials, search time)

  9. Behavioral inhibition [ Time Frame: at 2 years' corrected age ]
    Mommies and Babies task (number of trials, errors)

  10. Executive function [ Time Frame: at 2 years' corrected age ]
    Behavioral Rating Inventory of Executive Function - Preschool Version, higher scores indicate more problems

  11. Behavioral difficulties [ Time Frame: at 2 years' corrected age ]
    Infant-Toddler Symptom Checklist - Long Version, higher scores indicate more problems



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 21 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Inpatient in Brigham and Women's Hospital NICU
  • Gestational age 24 0/7 to 30 6/7 weeks
  • Chronologic age <21 days
  • Mother providing breast milk

Exclusion Criteria:

  • Major congenital anomaly
  • Severe fetal growth restriction (birth weight <3rd percentile by Olsen reference)
  • Necrotizing enterocolitis, intestinal perforation, other major gastrointestinal pathology
  • Triplets or higher order multiples
  • Plan for redirection of care and/or anticipated death
  • Clinically significant renal or hepatic dysfunction
  • Inborn error of metabolism
  • Fluid restriction <140 mL/kg/day for 3 or more days
  • Grade 3 or 4 intraventricular hemorrhage detected prior to enrollment
  • Anticipated transfer <36 weeks' postmenstrual age
  • Parents do not consent to use of pasteurized donor human milk
  • Infant in non-parental custody

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03977259


Contacts
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Contact: Tina Steele, RN, IBCLC 617-525-7376 tdufresne@bwh.harvard.edu
Contact: Emma Davitt, BA 617-732-9588 edavitt@bwh.harvard.edu

Locations
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United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Contact: Tina Steele, RN, IBCLC    617-525-7376    tdufresne@bwh.harvard.edu   
Contact: Emma Davitt, BA    617-732-9588    edavitt@bwh.harvard.edu   
Sponsors and Collaborators
Brigham and Women's Hospital
Investigators
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Principal Investigator: Mandy B Belfort, MD, MPH Brigham and Women's Hospital

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Responsible Party: Mandy Brown Belfort, MD MPH, Attending physician, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT03977259    
Other Study ID Numbers: 2019P000893
First Posted: June 6, 2019    Key Record Dates
Last Update Posted: June 10, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No current plans to share individual patient data. Future data sharing would involve de-identified data only and would require a data use agreement in accordance with hospital policy.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Premature Birth
Nutrition Disorders
Infant Nutrition Disorders
Disease
Neurodevelopmental Disorders
Pathologic Processes
Obstetric Labor, Premature
Obstetric Labor Complications
Pregnancy Complications
Mental Disorders