Human MilkNCT04025021
Targeted Breast Milk Fortification for Very Low Birth Weight Infants in the NICU
A study testing Targeted Fortification and The Miris Human Milk Analyzer in people with Human Milk and Neonate, run by MetroHealth Medical Center at 1 site in United States.
Trial summary
This study evaluates the effectiveness of individualized human milk fortification for very low birth weight (<1500 g) babies in the NICU (Neonatal Intensive Care Unit) to optimize their growth. Breast milk analysis will occur on a weekly basis using the Miris Human Milk Analyzer. Read more about this study
- Who is it for?
- Ages Up to 6 months
- Conditions the study is for
- Human Milk, Neonate, Breast Milk
- What is being tested?
- Targeted Fortification and The Miris Human Milk Analyzer
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2019to 31 Mar 2021
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 6 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Premature infants <1500 g
- Mother consenting to provide breast milk or use of donor breast milk
Who cannot join
- Infants with major congenital malformations
- Infants with medical conditions precluding them from having breast milk
- Mothers with medical conditions that preclude them form providing breast milk
- Insufficient breast milk supply
- Refusal of donor breast milk
- Mother is non-English speaking
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Targeted Fortification of Human Breast Milk and Adjustment of TPN for Very Low Birth Weight Infants to Optimize Growth and Nutrition Using the Miris Mid-infrared Human Milk Analyzer
This study evaluates the effectiveness of individualized human milk fortification for very low birth weight (<1500 g) babies in the NICU (Neonatal Intensive Care Unit) to optimize their growth. Breast milk analysis will occur on a weekly basis using the Miris Human Milk Analyzer. In the Control group, participants will receive standard TPN (total parenteral nutrition) and lipids and breast milk fortification according to MetroHealth's NICU guidelines. The Intervention group will receive TPN and lipids optimized depending on the results of breast milk analysis, followed by additional individualized fortification using additional microlipids and/or liquid protein to achieve the goal of 4g protein/kg/day and 100-130 kcal/kg/day.
Read the detailed description
Human milk has a variety of benefits for neonates, especially premature neonates, including a decreased risk of for necrotizing enterocolitis, sudden infant death syndrome (SIDS), respiratory syncytial virus (RSV) bronchiolitis, respiratory infections, and many other childhood conditions. There is variability in macronutrient and caloric content of breast milk between mothers, making it difficult to accurately quantify the nutritional content the breast milk is providing. The protein content varies by postnatal age, and the fat content varies temporally during a feed. Currently calculations use a standard value for caloric density and macronutrient content of breast milk, which is a reported average, but not necessarily specific to each individual mother. Human milk analysis has been used to address this variability. The Miris Human Milk Analyzer (HMA) is a mid-infrared analyzer and has been evaluated in many studies. It measures the macronutrient content of breast milk, providing values for protein, fat, carbohydrates, and calculated calories. By having this information available, the fortification added to breast milk can be tailored specifically to each mother's breast milk composition to meet each neonate's nutritional needs, and optimize growth.This will be a prospective randomized control study of preterm infants less than 1500 grams [very low birth weight (VLBW)] receiving human milk (maternal or donor) will be included. The control group will receive adjustment of total parenteral nutrition (TPN) per NICU guidelines as enteral feedings are advanced followed by standard fortification of human milk. The intervention group will have TPN (protein and lipids) adjusted based on analysis of human milk as feedings are advanced to provide goal 4g/kg/day of protein and 100-130 kcal/kg/day followed by targeted fortification of breast milk based on human milk analysis to continue to provide 4 g/kg/day of protein and 100-130 kcal/kg/day for once full feeds are achieved. The primary aim of this study is to evaluate the growth, anthropometric measurements, and body composition, to see if targeted fortification improves neonatal growth. By optimizing neonatal growth and nutrition there is potential to also have an impact on other morbidities and long term neurodevelopmental outcomes.
- Conditions
- Human Milk, Neonate, Breast Milk
- Being tested
- Targeted Fortification, The Miris Human Milk Analyzer
- Keywords
- Targeted Fortification, Human Milk Analysis, Neonatal Nutrition
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Targeted FortificationDietary supplement
The TPN and SMOF lipids will be optimized to provide a goal of 4 g/kg/day of protein, and 100-130kcal/kg/day. At 100 ml/kg/day of enteral feeds additional liquid protein and/or microlipids will be added to the breast milk to provide goal of 4 g/kg/day of protein and 100-130 kcal/kg/day. This will be determined by analysis of the milk and reported composition. They will continue targeted fortification for 4 weeks after achieving full feeds of 150 ml/kg/day.
The Miris Human Milk AnalyzerDevice
The Miris human milk analyzer is a mid infrared that reports the amount of energy absorbed at each wavelength. The amount of fat (grams), lactose (grams), total protein (grams), true protein (grams), and energy (kcal) per 100 ml will be reported.
| Study group | Role | What they receive |
|---|---|---|
| Control group (standard fortification) | No intervention | Breast milk will be fortified standard with Similac Human Milk Fortifier 1 packet: 50 ml breast milk at 50ml/kg/day enteral feeds, then 1 packet:25 ml breast milk at 75 ml/kg/day. As feedings are advanced to goal of 150 ml/kg/day, the TPN and SMOF lipids (Fat Emulsion Comprised of Soy Oil, Medium Chain Triglycerides, Olive Oil, and Fish Oil) will be decreased per standard management and NICU guidelines. |
| Intervention group (targeted fortification) | Experimental | Breast milk will be fortified standard with Similac Human Milk Fortifier 1 packet:
50 ml breast milk at 50ml/kg/day enteral feeds, then 1 packet:25 ml breast milk at 75 ml/kg/day. During this time, as the volume decreases, the TPN and SMOF lipids will be optimized to provide a goal of 4 g/kg/day of protein, and 100-130kcal/kg/day. At 100 ml/kg/day of enteral feeds additional liquid protein and/or microlipids will be added to the breast milk to provide goal of 4 g/kg/day of protein and 100-130 kcal/kg/day. This will be determined by analysis of the milk and reported composition. They will continue targeted fortification for 4 weeks after achieving full feeds of 150 ml/kg/day. Breast milk analysis will occur on a weekly basis immediately after birth for all infants enrolled in the study. Receives: Dietary Supplement: Targeted Fortification; Device: The Miris Human Milk Analyzer |
What is being measured
The primary outcome is the main question the study is designed to answer.
Body Composition
Body composition will be measured by air displacement plethysmography (PEAPod). As standardized assessment of body composition is relatively new in the preterm infant population, we are using clinical judgment to determine that a difference in fat free mass z-score (from data from Norris T, 2019) of 0.5 is clinically significant.
Measured: 4 weeks after baby reaches full feeds (150 mL/kg/day) or at NICU discharge
Secondary outcomes (5)
Weight Gain Velocity
Weight gain velocity, measured in grams/kg/day
Measured: From enrollment in study to 4 weeks after full feeds (150 mL/kg/day) or at NICU discharge.
Weight Gain
Daily weight will be obtained, measured in grams
Measured: From enrollment in study to 4 weeks at full feeds (150 mL/kg/day) or at NICU discharge.
Linear Growth
Weekly measurements of length will be obtained throughout the study, measured in centimeters
Measured: From enrollment in study to 4 weeks at full feeds (150 mL/kg/day) or at NICU discharge.
Head Circumference Growth
Weekly measurements of head circumference will be obtained throughout the study, measured in centimeters
Measured: From enrollment in study to 4 weeks at full feeds (150 mL/kg/day) or at NICU discharge.
Body Composition
Mid upper arm circumference (cm) or skinfold thickness (mm) will be measured weekly throughout the study and combined with length to calculate the body composition
Measured: From enrollment in study to 4 weeks at full feeds (150 mL/kg/day) or at NICU discharge.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2019
- Study start1 Oct 2019
- Primary completion31 Mar 2021
- Study completion31 Mar 2021
Why it stopped: Inability to enroll patients, sample collection
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Human MilkStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This study will be a randomized control trial with 2 arms: control group (standard fortification) or intervention group (targeted fortification) in a 1:1 allocation ratio. Allocation group will be stratified to four groups according to birth weight: \<750g, 751-1000g, 1001-1250g, 1251-1500g. This stratification is based upon our NICU feeding guideline, and will ensure that enrolled infants will receive comparable nutrition progression (e.g. NPO (nil per os) days, days of trophic feeds) throughout the study period. The allocation will be concealed in a sequentially numbered, opaque, sealed envelope, that will be opened after consent is obtained.
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- MetroHealth Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sharon Groh-Wargo, MetroHealth Medical Center
- Investigators
- Sharon Groh-Wargo, PhD, RDN, Principal investigator, MetroHealth Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04025021
- Sponsor's protocol ID
- 19-00200
- Status last verified
- Jan 2023
- First submitted
- 10 Jul 2019
- Last updated
- 23 Feb 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Section on Breastfeeding. Breastfeeding and the use of human milk. Pediatrics. 2012 Mar;129(3):e827-41. doi: 10.1542/peds.2011-3552. Epub 2012 Feb 27.
PubMed 22371471Martin CR, Ling PR, Blackburn GL. Review of Infant Feeding: Key Features of Breast Milk and Infant Formula. Nutrients. 2016 May 11;8(5):279. doi: 10.3390/nu8050279.
PubMed 27187450Fusch G, Kwan C, Kotrri G, Fusch C. "Bed Side" Human Milk Analysis in the Neonatal Intensive Care Unit: A Systematic Review. Clin Perinatol. 2017 Mar;44(1):209-267. doi: 10.1016/j.clp.2016.11.001. Epub 2016 Dec 29.
PubMed 28159207Tudehope DI. Human milk and the nutritional needs of preterm infants. J Pediatr. 2013 Mar;162(3 Suppl):S17-25. doi: 10.1016/j.jpeds.2012.11.049.
PubMed 23445843
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeted Fortification of Human Breast Milk and Adjustment of TPN for Very Low Birth Weight Infants to Optimize Growth and Nutrition Using the Miris Mid-infrared Human Milk Analyzer
- ClinicalTrials.gov ID
- NCT04025021
- Acronym / sponsor ID
- 19-00200
- Conditions
- Human Milk, Neonate, Breast Milk
- Keywords
- Targeted Fortification, Human Milk Analysis, Neonatal Nutrition
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Inability to enroll patients, sample collection
- Enrolment
- 3 participants (actual)
- Lead sponsor
- MetroHealth Medical CenterUniversity, hospital or other
- Study start
- 1 Oct 2019 (actual)
- Primary completion
- 31 Mar 2021 (actual)
- Study completion
- 31 Mar 2021 (actual)
- First posted
- 18 Jul 2019 (actual)
- Results
- Posted 23 Feb 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates the effectiveness of individualized human milk fortification for very low birth weight (<1500 g) babies in the NICU (Neonatal Intensive Care Unit) to optimize their growth. Breast milk analysis will occur on a weekly basis using the Miris Human Milk Analyzer. In the Control group, participants will receive standard TPN (total parenteral nutrition) and lipids and breast milk fortification according to MetroHealth's NICU guidelines. The Intervention group will receive TPN and lipids optimized depending on the results of breast milk analysis, followed by additional individualized fortification using additional microlipids and/or liquid protein to achieve the goal of 4g protein/kg/day and 100-130 kcal/kg/day.
Detailed description
Human milk has a variety of benefits for neonates, especially premature neonates, including a decreased risk of for necrotizing enterocolitis, sudden infant death syndrome (SIDS), respiratory syncytial virus (RSV) bronchiolitis, respiratory infections, and many other childhood conditions. There is variability in macronutrient and caloric content of breast milk between mothers, making it difficult to accurately quantify the nutritional content the breast milk is providing. The protein content varies by postnatal age, and the fat content varies temporally during a feed. Currently calculations use a standard value for caloric density and macronutrient content of breast milk, which is a reported average, but not necessarily specific to each individual mother. Human milk analysis has been used to address this variability. The Miris Human Milk Analyzer (HMA) is a mid-infrared analyzer and has been evaluated in many studies. It measures the macronutrient content of breast milk, providing values for protein, fat, carbohydrates, and calculated calories. By having this information available, the fortification added to breast milk can be tailored specifically to each mother's breast milk composition to meet each neonate's nutritional needs, and optimize growth.This will be a prospective randomized control study of preterm infants less than 1500 grams [very low birth weight (VLBW)] receiving human milk (maternal or donor) will be included. The control group will receive adjustment of total parenteral nutrition (TPN) per NICU guidelines as enteral feedings are advanced followed by standard fortification of human milk. The intervention group will have TPN (protein and lipids) adjusted based on analysis of human milk as feedings are advanced to provide goal 4g/kg/day of protein and 100-130 kcal/kg/day followed by targeted fortification of breast milk based on human milk analysis to continue to provide 4 g/kg/day of protein and 100-130 kcal/kg/day for once full feeds are achieved. The primary aim of this study is to evaluate the growth, anthropometric measurements, and body composition, to see if targeted fortification improves neonatal growth. By optimizing neonatal growth and nutrition there is potential to also have an impact on other morbidities and long term neurodevelopmental outcomes.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This study will be a randomized control trial with 2 arms: control group (standard fortification) or intervention group (targeted fortification) in a 1:1 allocation ratio. Allocation group will be stratified to four groups according to birth weight: <750g, 751-1000g, 1001-1250g, 1251-1500g. This stratification is based upon our NICU feeding guideline, and will ensure that enrolled infants will receive comparable nutrition progression (e.g. NPO (nil per os) days, days of trophic feeds) throughout the study period. The allocation will be concealed in a sequentially numbered, opaque, sealed envelope, that will be opened after consent is obtained.
| Arm | Type | Receives |
|---|---|---|
| Control group (standard fortification) | No intervention | –Breast milk will be fortified standard with Similac Human Milk Fortifier 1 packet: 50 ml breast milk at 50ml/kg/day enteral feeds, then 1 packet:25 ml breast milk at 75 ml/kg/day. As feedings are advanced to goal of 150 ml/kg/day, the TPN and SMOF lipids (Fat Emulsion Comprised of Soy Oil, Medium Chain Triglycerides, Olive Oil, and Fish Oil) will be decreased per standard management and NICU guidelines. |
| Intervention group (targeted fortification) | Experimental | Dietary Supplement: Targeted Fortification, Device: The Miris Human Milk AnalyzerBreast milk will be fortified standard with Similac Human Milk Fortifier 1 packet: 50 ml breast milk at 50ml/kg/day enteral feeds, then 1 packet:25 ml breast milk at 75 ml/kg/day. During this time, as the volume decreases, the TPN and SMOF lipids will be optimized to provide a goal of 4 g/kg/day of protein, and 100-130kcal/kg/day. At 100 ml/kg/day of enteral feeds additional liquid protein and/or microlipids will be added to the breast milk to provide goal of 4 g/kg/day of protein and 100-130 kcal/kg/day. This will be determined by analysis of the milk and reported composition. They will continue targeted fortification for 4 weeks after achieving full feeds of 150 ml/kg/day. Breast milk analysis will occur on a weekly basis immediately after birth for all infants enrolled in the study. |
Who may qualify
- Ages
- Up to 6 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- Premature infants <1500 g
- Mother consenting to provide breast milk or use of donor breast milk
Key exclusion criteria (6 listed)
- Infants with major congenital malformations
- Infants with medical conditions precluding them from having breast milk
- Mothers with medical conditions that preclude them form providing breast milk
- Insufficient breast milk supply
- Refusal of donor breast milk
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Targeted FortificationThe TPN and SMOF lipids will be optimized to provide a goal of 4 g/kg/day of protein, and 100-130kcal/kg/day. At 100 ml/kg/day of enteral feeds additional liquid protein and/or microlipids will be added to the breast milk to provide goal of 4 g/kg/day of protein and 100-130 kcal/kg/day. This will be determined by analysis of the milk and reported composition. They will continue targeted fortification for 4 weeks after achieving full feeds of 150 ml/kg/day. | Dietary supplement | Intervention group (targeted fortification) |
| The Miris Human Milk AnalyzerThe Miris human milk analyzer is a mid infrared that reports the amount of energy absorbed at each wavelength. The amount of fat (grams), lactose (grams), total protein (grams), true protein (grams), and energy (kcal) per 100 ml will be reported. | Device | Intervention group (targeted fortification) |
Primary outcome
Body Composition
Time frame: 4 weeks after baby reaches full feeds (150 mL/kg/day) or at NICU discharge
Body composition will be measured by air displacement plethysmography (PEAPod). As standardized assessment of body composition is relatively new in the preterm infant population, we are using clinical judgment to determine that a difference in fat free mass z-score (from data from Norris T, 2019) of 0.5 is clinically significant.
5 secondary outcomes
Weight Gain Velocity
Time frame: From enrollment in study to 4 weeks after full feeds (150 mL/kg/day) or at NICU discharge.
Weight Gain
Time frame: From enrollment in study to 4 weeks at full feeds (150 mL/kg/day) or at NICU discharge.
Linear Growth
Time frame: From enrollment in study to 4 weeks at full feeds (150 mL/kg/day) or at NICU discharge.
Head Circumference Growth
Time frame: From enrollment in study to 4 weeks at full feeds (150 mL/kg/day) or at NICU discharge.
Body Composition
Time frame: From enrollment in study to 4 weeks at full feeds (150 mL/kg/day) or at NICU discharge.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22371471Section on Breastfeeding. Breastfeeding and the use of human milk. Pediatrics. 2012 Mar;129(3):e827-41. doi: 10.1542/peds.2011-3552. Epub 2012 Feb 27.
- Background: PubMed 27187450Martin CR, Ling PR, Blackburn GL. Review of Infant Feeding: Key Features of Breast Milk and Infant Formula. Nutrients. 2016 May 11;8(5):279. doi: 10.3390/nu8050279.
- Background: PubMed 28159207Fusch G, Kwan C, Kotrri G, Fusch C. "Bed Side" Human Milk Analysis in the Neonatal Intensive Care Unit: A Systematic Review. Clin Perinatol. 2017 Mar;44(1):209-267. doi: 10.1016/j.clp.2016.11.001. Epub 2016 Dec 29.
- Background: PubMed 23445843Tudehope DI. Human milk and the nutritional needs of preterm infants. J Pediatr. 2013 Mar;162(3 Suppl):S17-25. doi: 10.1016/j.jpeds.2012.11.049.
- Miris HMA, Human Milk Analyzer websiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Healthy Volunteers
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sharon Groh-Wargo, PhD, RDN principal investigator
MetroHealth Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Targeted Fortification and The Miris Human Milk Analyzer in people with Human Milk and Neonate, run by MetroHealth Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 23 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Body Composition (time frame: 4 weeks after baby reaches full feeds (150 mL/kg/day) or at NICU discharge). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04025021, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2023.