Use of Human Milk Cream to Decrease Length of Stay in Extremely Premature Infants

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Brief Title

Use of Human Milk Cream to Decrease Length of Stay in Extremely Premature Infants

Official Title

Post-Discharge Evaluation of Human Milk Cream Study Infants at 18 to 24 Month CGA: A Randomized Trial of the Use of Human Milk Cream to Decrease Length of Stay in Extremely Premature Infants

Brief Summary

      At present, widespread use of the human milk-based caloric supplement (cream) has not
      occurred, particularly in infants with bronchopulmonary dysplasia (BPD), and further data are
      needed to support its adoption as a standard care practice.

      The investigators hypothesize that infants who receive an exclusive human milk (HM)-based
      diet with the addition of a HM-derived cream caloric supplement (Cream group) will have a
      shorter length of initial hospital stay compared to infants receiving the standard regimen of
      an exclusive HM-based diet (Control group). The investigators hypothesize that the effects of
      the cream caloric supplement will be greater in the subgroup of infants who develop BPD so
      the relationship will be evaluated between Cream Supplement study group and postmenstrual age
      (PMA) at discharge and the incidence of BPD. Investigators will also evaluate the
      post-hospital discharge growth, body composition, and neurodevelopmental outcomes at 18 to 24
      months CGA of the infants 500-1250 grams BW who received an exclusive human milk diet
      including cream supplement or control in the NICU.
    

Detailed Description

      The primary hypothesis of the study is that infants who receive an exclusive HM-based diet
      with the addition of a HM-derived cream caloric (Cream group) will have a shorter length of
      initial hospital stay compared to infants receiving the standard regimen of an exclusive
      HM-based diet (Control group).

      The study design is a randomized controlled trial in preterm infants (birth weight 500-1250g)
      comparing the use of a human milk cream supplement added to an exclusive HM-based diet (Cream
      group) to an exclusive HM-based diet without the use of a cream supplement (Control group).
      Each study group will use mother's own milk, donor HM if needed (donor HM should be obtained
      from a Human Milk Banking Association of North America (HMBANA) or Prolacta milk bank that
      uses Holder method pasteurization and does not homogenize the milk) and a donor human
      milk-derived fortifier (Prolact+ H2MF®) according to the study feeding protocol. Feeding will
      be done by protocol in which fortification will begin when the baby is receiving 60 mL/kg/day
      of enteral nutrition. The randomization will be performed in blocks (block size to remain
      blinded) without the use of stratification variables except for study site. While blinding of
      study groups is always desirable in randomized studies, because of the nature of the
      interventions and the varying methods by which the nutrition is prepared and delivered in
      different units, this will not be possible for this study.

      Sample Size:

      The number of infants to be included in this study is based on the primary endpoint of a
      reduction in the length of hospital stay in days by 12.1 days with a standard deviation of 31
      days. With a two-tailed 5% significance level and 80% power, a sample size of 210 (n=105 per
      group) is needed to demonstrate a difference of this magnitude between the 2 study groups.

      Study Duration:

      All study infants will be followed until discharge or transfer from the medical institution
      or death (hospital stay is an expected average of 10 weeks). Infants will be transitioned
      completely off an exclusive HM-based diet no earlier than 34 weeks PMA, however, infants will
      be followed until hospital discharge (total of an estimated average of 10 weeks) to collect
      anthropometric and study outcome data.

      Study Population:

      Each study subject must meet all of the indicated inclusion criteria and none of the
      exclusion criteria.

      Study Procedure:

      After eligibility of the infant is determined and informed consent is obtained from the
      parent or legal guardian, infants will be randomized using a stratified (by study site) block
      scheme noted above into either the group that will receive human milk cream (Cream
      Supplement) or not (Control). All study infants will follow the study feeding protocol. The
      use of fortifier, both the timing of initiation and advancing of feeds will be per study
      protocol as tolerated. Study infants are to receive only an exclusive HM-based diet and they
      are not to deviate from the protocol (receiving formula, medium chain triglyceride (MCT) oil,
      liquid protein supplement, bovine fortifier, etc). Once breast milk (either mother's or
      donor) fortification is initiated and infants reach feeds of at least 100 mL/kg/day, for
      infants randomized to the cream group, they will start receiving the cream supplement per
      protocol. HM cream supplement will be added to feeds to provide an additional 2 kcal/oz of
      energy (amount of cream to add equals amount of unfortified milk x 0.04 rounded to the
      nearest full mL). For example, 4 mL of cream would be added to 96 mL of unfortified milk and
      then the fortifier is added to the milk-cream mixture. The Control group will not receive
      cream and will be fed per Table 1. Infants will be followed and studied until discharge,
      transfer to a non-study institution, removal from the study or death. Starting no sooner than
      34 weeks PMA, infants will be transitioned over 5 days to either mother's milk with bovine
      fortifier or transitional formula according to investigative site's standard of care. All
      infants will have a brain MRI at "term equivalent" age (if this is routine practice at the
      study site). Infants will also have body composition determined by dual energy x-ray
      absorptiometry (DXA) scan (if available at the study site). One outpatient study visit will
      occur at 18 to 24 months post discharge to obtain anthropometric data, interim medical
      history, demographic and socioeconomic information, and nutrition history of the child since
      discharge (formula, human milk, vitamins, and medications). A neurodevelopmental evaluation
      (The Bayley Scales of Infant Development III) will also be performed by a certified tester
      during this visit. In addition, data from NICU hospitalizations will be collected during this
      visit. Data collection will include: demographics (gestational age, birth weight, gender, and
      race), APGAR scores, nutrition and feeding related issues (parental nutrition and
      constituents, feeding regimen, feeding intolerance), growth parameters (weight, length, and
      head circumference), medications (caffeine, furosemide, chlorothiazide, hydrocortisone,
      dexamethasone, insulin, and dopamine), nutrition related labs, and morbidities
      (intraventricular hemorrhage, patent ductus arteriosus, necrotizing enterocolitis,
      spontaneous intestinal perforation, episodes of sepsis, chronic lung disease).

      Anthropometric Measurements:

      At each study site, designated study personnel (preferably no more than 3 consistent trained
      personnel), will be responsible for weekly anthropometric measurements. The personnel will be
      trained or will demonstrate proficiency in obtaining anthropometric measurements using proper
      equipment. They will take weekly weights, lengths using only a study length board to be
      provided, and head circumference measurements. Each measurement will be taken twice and the
      average of the two will be recorded (for the weekly measurement).

      Human Milk Samples:

      Three times a week (on 3 separate days), samples of the human milk (either mother's own or
      donor) per study infant will be obtained (4 mL in a syringe) and will be stored for future
      macronutrient analysis after study completion. The samples should be stored at -20 degrees C.
      The sample should be from a batch of unfortified human milk and should represent the milk to
      be used to prepare 24 hours of feedings. Stored samples will be sent to the coordinating
      study center for post-study analysis.

      Microbiome Samples:

      For all enrolled infants, tracheal aspirates (if intubated in the first 24 hours of life) and
      stool for post-study evaluation of infants' airway and gastrointestinal microbiome will be
      collected as feasible. A recent study by Lohmann et al showed that reduced diversity of the
      microbiome may be an important factor in the development of BPD. In addition, studies have
      shown that human milk positively affects the microbiome of premature infants. Tracheal
      aspirates will be obtained per study protocol if infants are intubated at birth to 24 hours
      of age, 48-72 hours of age, 7 days of age, and 28 days of age or at time of extubation if
      sooner. Any tracheal aspirate obtained within this time frame is acceptable (samples are of
      convenience with routine suctioning and care). Stool samples will be obtained per study
      protocol at the 1st, 2nd, 3rd, and 4th weeks of life. The infants' first stool (meconium)
      should be obtained. Samples will be collected and frozen at -80 degrees C and will be sent to
      the coordinating study center for post-study microbiome analysis.
    


Study Type

Interventional


Primary Outcome

Length of Stay

Secondary Outcome

 Incidence of Bronchopulmonary dysplasia and relationship to postmenstrual age at discharge in infants who received cream supplement

Condition

Bronchopulmonary Dysplasia

Intervention

Cream Supplement group

Study Arms / Comparison Groups

 Cream Supplement group
Description:  Infants randomized to the cream supplement group will receive an exclusive HM-based diet with the addition of a HM-derived cream caloric supplement.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Dietary Supplement

Estimated Enrollment

210

Start Date

June 10, 2015

Completion Date

December 1, 2020

Primary Completion Date

June 25, 2019

Eligibility Criteria

        Inclusion Criteria:

          -  Birth weight 500-1250g.

          -  Must be likely to be able to adhere to a feeding protocol involving mother's own
             milk/donor milk that will include fortification using HM-based product (Prolact+H2MF®)
             and, potentially, human milk-based cream supplement.

          -  Enteral feeding must begin before day 14 of life and parenteral nutrition must be
             started by day 2 of life.

          -  Informed consent obtained from parent or legal guardian prior to reaching 100
             ml/kg/day of fortified feeds. Consent should be obtained as soon as possible for
             eligible infants to collect tracheal aspirates (if intubated) and meconium stool.
             However, consent must be obtained prior to reaching 100 ml/kg/day of fortified feeds
             because this is when randomization will occur.

        Exclusion Criteria:

          -  Unlikely to survive the study period.

          -  Enrolled in another clinical study affecting nutritional management during the study
             period.

          -  Decision to not start minimum enteral feed before day 14 of life or parenteral
             nutrition before day 2 of life.

          -  Presence of clinically significant congenital heart disease or other major congenital
             malformation.

          -  Presence prior to enrollment of intestinal perforation or Stage 2 Necrotizing
             enterocolitis prior to tolerating fortified feeds.

          -  Reasonable likelihood of early transfer to a non-study institution.

          -  Unable to participate for any reason based on the decision of the study investigator.
      

Gender

All

Ages

N/A - 14 Days

Accepts Healthy Volunteers

No

Contacts

Amy B Hair, MD, , 

Location Countries

Austria

Location Countries

Austria

Administrative Informations


NCT ID

NCT02475434

Organization ID

H-37231


Responsible Party

Principal Investigator

Study Sponsor

Baylor College of Medicine

Collaborators

 Prolacta Bioscience

Study Sponsor

Amy B Hair, MD, Principal Investigator, Texas Children's Hospital, Baylor College of Medicine


Verification Date

May 2020