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

Related Clinical Trial
PAL to Improve Oral Feeding for Infants With Chronic Lung Disease Exposure to Plasticisers in the Neonatal Intensive Care Unit Implementation of a Consensus-Based Discharge Protocol for Preterm Infants With Lung Disease Prediction for Bronchopulmonary Dysplasia Baby Lung: an Observational Study The Role of Transthoracic Echocardiography in Diagnosis of Pulmonary Hypertension of Infants With Bronchopulmonary Dysplasia Body Weight Growth After Birth and Bronchopulmonary Dysplasia Outcome of Extremely Preterm Infants Who Received Systemic Postnatal Corticosteroid for Bronchopulmonary Dysplasia Comparison of the Acute Effects of Chest Physiotherapy Methods Applied in Different Positions in Preterm Newborns Maintaining Optimal HVNI Delivery Using Automatic Titration of Oxygen in Preterm Infants Impact of Steroid, Diuretic, and Fluid Use on BPD Outcomes Ultrasound Assessment of Diaphragmatic Function in Infants With BPD Ventilation-perfusion (V/Q) Ratio and Alveolar Surface Area in Preterm Infants Nasal High-frequency Oscillatory Ventilation (NHFOV) for Ventilated Newborn Infants With BPD Prone Versus Supine Positioning and the Impact on Bronchopulmonary Dysplasia in Very Low Birth Weight Infants. Intratracheal Budesonide With Surfactant to Prevent Bronchopulmmonary Dysplasia. NAVA vs. CMV Crossover in Severe BPD CPAP Or Nasal Cannula Oxygen for Preterm Infants: A Randomized Controlled Trial Lung Ultrasound for Early Identification of Preterm Infants With Bronchopulmonary Dysplasia Phase 1b/2 Study on AT-100 Intervention (rhSP-D) in Preterm Neonates at High Risk for Development of Bronchopulmonary Dysplasia (BPD) Inhaled Treatment for Bronchopulmonary Dysplasia Phase 1 Trial of Inhaled Tobramycin in BPD The Budesonide in Babies (BiB) Trial Follow-up Results of Newborns With Tracheostomy Safety of Sildenafil in Premature Infants With Severe Bronchopulmonary Dysplasia Prolonged Outcomes After Nitric Oxide (PrONOx) A Study of Tobacco Smoke and Children With Respiratory Illnesses Delivery Room CPAP in Extremely Low Birth Weight Infants Dexamethasone Therapy in VLBW Infants at Risk of CLD Palivizumab for Prevention of Severe Respiratory Syncytial Virus Infection in Russian Children Estimating Length of Endotracheal Tube Insertion Using Gestational Age or Nasal-Tragus Length in Newborn Infants MRI as a Means to Measure Lung Function: Non-Invasive Imaging in Neonates and Children Seattle-PAP Bubble Nasal CPAP and Work of Breathing High Frequency Oscillatory Ventilation Combined With Intermittent Sigh Breaths: Effects on Blood Oxygenation and Stability of Oxygenation Comparing Two Different Modes of Ventilation in Pretem Neonates Bilevel VG and PRVC High Frequency Ventilation in Premature Infants (HIFI) Early Caffeine in Preterm Neonates High Frequency Oscillatory Ventilation Combined With Intermittent Sigh Breaths: Effects on Lung Volume Monitored by Electric Tomography Impedance. Functional and Lymphocytic Markers of Respiratory Morbidity in Hyperoxic Preemies Vitamin A Supplementation for Extremely-Low-Birth-Weight Infants Non-invasive Respiratory Support in Preterm Infants Pilot Trial of Surfactant Booster Prophylaxis For Ventilated Preterm Neonates Randomized Trial of Nasal Continuous Positive Airway Pressure or Synchronized Nasal Ventilation in Premature Infants. The Effect of Surfactant Dose on Outcomes in Preterm Infants With RDS Work of Breathing During Non-invasive Ventilation in Premature Neonates Inhaled Nitric Oxide for Preventing Chronic Lung Disease in Premature Infants Intratracheal Budesonide/Surfactant Prevents BPD Bronchopulmonary Disease (BPD) Patient Registry Premature Birth and Its Sequelae in Women Inhaled NO in Prevention of Chronic Lung Disease The Effects of Position on the Oxygenation Instability of Premature Infants as Documented by SpO2 Histograms Trial of Late Surfactant to Prevent BPD: A Pilot Study in Ventilated Preterm Neonates Receiving Inhaled Nitric Oxide Continuous Positive Airway Pressure Via Binasal Prong vs Nasal Mask: a Randomised Controlled Trial Randomized Trial of Hydrocortisone in Very Preterm High-Risk Infants Early NCPAP Before Surfactant Treatment in Very Preterm Infants With RDS Exosurf Neonatal and Survanta for Treatment of Respiratory Distress Syndrome Continuous Versus Intermittent Bolus Feeding in Very Preterm Infants – Effect on Respiratory Morbidity Feasibility and Impact of Volume Targeted Ventilation in the Delivery Room Growth of Airways and Lung Tissues in Premature and Healthy Infants Duration of Continuous Positive Airway Pressure and Pulmonary Function Testing in Preterm Infants Assessment of Lung Structure and Function of Infants Born Prematurely Post-hospitalization Nursing Effectiveness (PHONE) Study Assessment of the Pulmonary Diffusion Capacity in Healthy Infants and Infants With Chronic Lung Disease NCPAP + Heliox as a Treatment for Infant Respiratory Distress Syndrome (RDS) Neurotrophin Expression in Infants as a Predictor of Respiratory and Neurodevelopmental Outcomes Inhaled Beclomethasone to Prevent Chronic Lung Disease Work of Breathing in Premature Infants at Discharge Efficacy of Recombinant Human Clara Cell 10 Protein (rhCC10) Administered to Premature Neonates With Respiratory Distress Syndrome Hydrocortisone for BPD Clinic Features and Outcome of BPD (SGBPD) Neolifes Heart – Pulmonary Hypertension in Preterm Children Thrombocytopoiesis and Platelet Homeostasis in Infants With Bronchoplumonary Dysplasia Management of Hyponatremia in Preterm Infants on Diuretics Steroids and Surfactant in Extremely Low Gestation Age Infants Dose Escalation Trial Respiratory Outcome at Adolescence of Very Low Birthweight Infants Surfactant Administration During Spontaneous Breathing Determining the Effect of Spironolactone on Electrolyte Supplementation in Preterm Infants With Chronic Lung Disease Developmental Sequelae of Severe Chronic Lung Disorders Long-term Safety and Efficacy Follow-up Study of PNEUMOSTEM® in Patients Who Completed PNEUMOSTEM® Phase-I Study Indoor Air Quality and Respiratory Morbidity in School-Aged Children With BPD Study of Nasal Ventilation In Preterm Infants To Decrease Time on The Respirator Improving Prematurity-Related Respiratory Outcomes at Vanderbilt Study of Inhaled Nitric Oxide (iNO) and Respiratory Outcomes in Late Preterm Infants Follow-up Study of Safety and Efficacy in Subjects Who Completed PNEUMOSTEM® Phase II (MP-CR-012) Clinical Trial Follow-up Safety and Efficacy Evaluation on Subjects Who Completed PNEUMOSTEM® Phase-II Clinical Trial Tidal Neonatal NO, Vitamins A and D, and Infant Lung Disease – The AD-ON Study Nasal Mask and Prong Use in Non-invasive Ventilation for Newborns Azithromycin in the Prevention of Lung Injury in Premature Newborn Randomized Control Trial: Synchronized Non-invasive Positive Pressure Ventilation Versus Non Synchronized Non Invasive Positive Pressure Ventilation in Extremely Low Birth Weight Infants Neurally Adjusted Ventilatory Assist vs Proportional Assist Ventilation MRI in BPD Subjects A Safety Study of IV Stem Cell-derived Extracellular Vesicles (UNEX-42) in Preterm Neonates at High Risk for BPD Hypercapnia and Its Association With Long-term Respiratory Morbidities in Premature Infants With Chronic Lung Disease Early Versus Late Caffeine for ELBW Newborns Assessment of Lung Aeration at Birth MRI of Lung Structure and Function in Preterm Children BPD Saturation TARgeting Use of Human Milk Cream to Decrease Length of Stay in Extremely Premature Infants Effect of Synchronized vs. Continuous HFNC Using NAVA on WOB in Infants With BPD Antecedents of Bronchopulmonary Dysplasia Pulmonary Outcomes of Bronchopulmonary Dysplasia in Young Adulthood Aerosolized Albuterol Use in Severe BPD Late Sequelae of Bronchopulmonary Dysplasia Montelukast in Very Low Birthweight Infants Preterm Infant Inhaled Albuterol Dosing 129Xe MRI in Pediatric Population With BPD Investigation of Polymorphisms in Bronchopulmonary Dysplasia In Turkish Population Pulmonary MRI of Ex-preterm Children With and Without BPD To Understand Risk of Emphysematous Changes Comparison of Classification Standards of BPD in Premature Infants Inhaled Corticosteroids for Treatment of Bronchopulmonary Dysplasia Safety of Sildenafil in Premature Infants Phase II Pilot Study of Early Cortisol Replacement to Prevent Bronchopulmonary Dysplasia Intratracheal Umbilical Cord-derived Mesenchymal Stem Cells for Severe Bronchopulmonary Dysplasia Phase III Randomized, Double-Blind Study of Dexamethasone Vs Dexamethasone/Methylprednisolone Vs Placebo for Bronchopulmonary Dysplasia Impact of an Exercise Program for Children Aged 4 to 6 Years With Bronchopulmonary Dysplasia Trial II of Lung Protection With Azithromycin in the Preterm Infant Forced Oscillometry in Infants With Bronchopulmonary Dysplasia The Efficacy and Safety of Montelukast Sodium in the Prevention of Bronchopulmonary Dysplasia L-citrulline and Pulmonary Hypertension Associated With Bronchopulmonary Dysplasia The Role of Anti-Reflux Surgery for Gastroesophageal Reflux Disease in Premature Infants With Bronchopulmonary Dysplasia Enteral Zinc to Improve Growth in Infants at Risk for Bronchopulmonary Dysplasia Fluid Filled Lung Oxygenation Assistance Trial Trial of Late Surfactant for Prevention of Bronchopulmonary Dysplasia Predictors of Pulmonary Hypertension Risk in Premature Infants With Bronchopulmonary Dysplasia Exogenous Surfactant in Very Preterm Neonates in Prevention of Bronchopulmonary Dysplasia Follow-Up Study of Safety and Efficacy of Pneumostem® in Premature Infants With Bronchopulmonary Dysplasia Risk Factors in Bronchopulmonary Dysplasia (Newborn Lung Project) Pilot Study of Topical Steroid for Prevention of Chronic Lung Disease in Extremely Premature Infants. Bronchopulmonary Dysplasia: From Neonatal Chronic Lung Disease to Early Onset Adult COPD Gastrin-Releasing Peptide and Bronchopulmonary Dysplasia Benchmarking Initiative to Reduce Bronchopulmonary Dysplasia Physiologic Definition of Bronchopulmonary Dysplasia Safety and Efficacy of PNEUMOSTEM® in Premature Infants at High Risk for Bronchopulmonary Dysplasia (BPD) – a US Study Inhaled Nitric Oxide for Pulmonary Hypertension and Bronchopulmonary Dysplasia Human Mesenchymal Stem Cells For Infants At High Risk For Bronchopulmonary Dysplasia SURFAXIN® Treatment for Prevention of Bronchopulmonary Dysplasia (BPD) in Very Low Birth Weight (VLBW) Infants. Safety of Furosemide in Premature Infants at Risk of Bronchopulmonary Dysplasia (BPD) Mesenchymal Stem Cells for The Treatment of Bronchopulmonary Dysplasia in Infants p16Ink4a in Bronchopulmonary Dysplasia in Children Transpyloric Feeding in Severe Bronchopulmonary Dysplasia Follow-Up Study of Mesenchymal Stem Cells for Bronchopulmonary Dysplasia Phase 1 Intravenous Citrulline for the Prevention of Bronchopulmonary Dysplasia in Preterm Infants Epidemiological Study for Bronchopulmonary Dysplasia (BPD) in China PREMILOC Trial to Prevent Bronchopulmonary Dysplasia in Very Preterm Neonates Stem Cells for Bronchopulmonary Dysplasia Hydrotherapy in Premature Infants With Bronchopulmonary Dysplasia Inhaled Nitric Oxide (INO) for the Prevention of Bronchopulmonary Dysplasia (BPD) in Preterm Infants Prospective Study on Plasma Pro-endothelin-1 in Predicting Bronchopulmonary Dysplasia Interest of Pulmonary Ultrasound to Predict Evolution Towards Bronchopulmonary Dysplasia in Premature Infants at Gestational Age Less Than or Equal to 34 Weeks of Gestation Safety and Efficacy Evaluation of PNEUMOSTEM® Treatment in Premature Infants With Bronchopulmonary Dysplasia Inhaled Extra-fine Hydrofluoalkane-beclomethasone (QVAR) in Premature Infants With Bronchopulmonary Dysplasia (BPD) Efficacy and Safety of Inhaled Budesonide in Very Preterm Infants at Risk for Bronchopulmonary Dysplasia Study to Justify Steroid Use in Preterm Neonates to Prevent Bronchopulmonary Dysplasia Efficacy of Adding Budesonide to Poractant Alfa to Prevent Bronchopulmonary Dysplasia. Human Mesenchymal Stem Cells For Bronchopulmonary Dysplasia Human Mesenchymal Stem Cells For Moderate and Severe Bronchopulmonary Dysplasia Genetic Susceptibility for Bronchopulmonary Dysplasia in Preterm Infants Respiratory Management of Preterm Infants and Bronchopulmonary Dysplasia

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


Primary Outcome

Length of Stay

Secondary Outcome

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


Bronchopulmonary Dysplasia


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.


* 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


Start Date

June 10, 2015

Completion Date

December 31, 2022

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

          -  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

          -  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.




N/A - 14 Days

Accepts Healthy Volunteers



Amy B Hair, MD, , 

Location Countries


Location Countries


Administrative Informations



Organization ID


Responsible Party

Principal Investigator

Study Sponsor

Baylor College of Medicine


 Prolacta Bioscience

Study Sponsor

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

Verification Date

April 2022