Preterm BirthNCT03977259
Targeting Human Milk Fortification to Improve Preterm Infant Growth and Brain Development
A study testing Individually targeted fortification in people with Preterm Birth and Breast Milk Expression, run by Brigham and Women's Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 day to 21 days
- Conditions the study is for
- Preterm Birth, Breast Milk Expression, Nutrition Disorder, Infant
- What is being tested?
- Individually targeted fortification
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 130 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Jan 2020to 31 Dec 2030
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 1 day to 21 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham and Women's Hospital
Boston, Massachusetts, 02115
About this study
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.
Read the 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 <31 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.
- Conditions
- Preterm Birth, Breast Milk Expression, Nutrition Disorder, Infant, Brain Development Abnormality, Neurodevelopmental Disorders
- Being tested
- Individually targeted fortification
- Medical subject headings
- Premature Birth, Breast Milk Expression, Infant Nutrition Disorders, Neurodevelopmental Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Individually targeted fortificationOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Standard fortification | No intervention | 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. |
| Individually targeted fortification | Experimental | Standard of care fortification plus extra protein and/or calories to ensure that "base" milk has protein 1 g/dL and calories 67/dL. Receives: Other: Individually targeted fortification |
What is being measured
The primary outcome is the main question the study is designed to answer.
Weight
Weight z-score
Measured: at study endpoint (36 weeks' postmenstrual age or discharge)
Length
Length z-score
Measured: at study endpoint (36 weeks' postmenstrual age or discharge)
Fat free mass
Fat free mass estimated with air displacement plethysmography (z-score)
Measured: at study endpoint (36 weeks' postmenstrual age or discharge)
Total brain volume
Total brain volume by MRI
Measured: at term equivalent age (38 to 41 weeks' postmenstrual age)
Cerebellar volume
Cerebellar volume by MRI
Measured: at term equivalent age (38 to 41 weeks' postmenstrual age)
Bayley-III cognitive score
Scaled composite score (continuous), higher score indicates better performance, range of possible scores 55-145
Measured: at 2 years' corrected age
Bayley-III motor score
Scaled composite score (continuous), higher score indicates better performance, range of possible scores 46-154
Measured: at 2 years' corrected age
Secondary outcomes (11)
Fat mass
Fat mass estimated with air displacement plethysmography (z-score)
Measured: at study endpoint (36 weeks' postmenstrual age or discharge)
Weight
Weight z-score
Measured: at 2 years' corrected age
Height
Height z-score
Measured: at 2 years' corrected age
Low Bayley-III cognitive score
Scaled composite score <85 (>1 standard deviation below the normative mean)
Measured: At 2 years' corrected age
Low Bayley-III motor score
Scaled composite score <85 (>1 standard deviation below the normative mean)
Measured: At 2 years' corrected age
Bayley-III language score
Scaled composite score (continuous), higher score indicates better performance, range of possible scores 46-154
Measured: At 2 years' corrected age
Bayley-III language score
Scaled composite score <85 (>1 standard deviation below the normative mean)
Measured: At 2 years' corrected age
Spacial working memory
Spin the Pots task (number of trials, search time)
Measured: at 2 years' corrected age
Behavioral inhibition
Mommies and Babies task (number of trials, errors)
Measured: at 2 years' corrected age
Executive function
Behavioral Rating Inventory of Executive Function - Preschool Version, higher scores indicate more problems
Measured: at 2 years' corrected age
Behavioral difficulties
Infant-Toddler Symptom Checklist - Long Version, higher scores indicate more problems
Measured: at 2 years' corrected age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2019
- Study start31 Jan 2020
- Primary completion31 Aug 2027 (estimated)
- Study completion31 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Preterm BirthStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- 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
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 130 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mandy Brown Belfort, MD MPH, Brigham and Women's Hospital
- Investigators
- Mandy B Belfort, MD, MPH, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03977259
- Sponsor's protocol ID
- 2019P000893
- Status last verified
- Jun 2026
- First submitted
- 5 Jun 2019
- Last updated
- 15 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: 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.
Publications
Belfort MB, Ahtam B, Bell KA, Berger P, Cherkerzian S, Ellard D, Foster L, Fusch C, Gagoski B, Grant PE, Kuncham M, Pepin H, Solti M, Steele T, Woodward L, Inder T. Individually Targeted Human Milk Fortification: A Randomized Clinical Trial. JAMA Pediatr. 2026 Sep 14:e264220. doi: 10.1001/jamapediatrics.2026.4220. Online ahead of print.
PubMed 42734908Belfort MB, Woodward LJ, Cherkerzian S, Pepin H, Ellard D, Steele T, Fusch C, Grant PE, Inder TE. Targeting human milk fortification to improve very preterm infant growth and brain development: study protocol for Nourish, a single-center randomized, controlled clinical trial. BMC Pediatr. 2021 Apr 9;21(1):167. doi: 10.1186/s12887-021-02635-x.
PubMed 33836708
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeting Human Milk Fortification to Improve Preterm Infant Growth and Brain Development
- ClinicalTrials.gov ID
- NCT03977259
- Acronym / sponsor ID
- 2019P000893
- Conditions
- Preterm Birth, Breast Milk Expression, Nutrition Disorder, Infant, Brain Development Abnormality, Neurodevelopmental Disorders
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 130 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Study start
- 31 Jan 2020 (actual)
- Primary completion
- 31 Aug 2027 (estimated)
- Study completion
- 31 Dec 2030 (estimated)
- First posted
- 6 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 <31 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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard fortification | No intervention | –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. |
| Individually targeted fortification | Experimental | Other: Individually targeted fortificationStandard of care fortification plus extra protein and/or calories to ensure that "base" milk has protein 1 g/dL and calories 67/dL. |
Who may qualify
- Ages
- 1 day to 21 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (12 listed)
- 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
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 |
|---|---|---|
| Individually targeted fortificationAbbott 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. | Other | Individually targeted fortification |
Primary outcome
Weight
Time frame: at study endpoint (36 weeks' postmenstrual age or discharge)
Weight z-score
Length
Time frame: at study endpoint (36 weeks' postmenstrual age or discharge)
Length z-score
Fat free mass
Time frame: at study endpoint (36 weeks' postmenstrual age or discharge)
Fat free mass estimated with air displacement plethysmography (z-score)
Total brain volume
Time frame: at term equivalent age (38 to 41 weeks' postmenstrual age)
Total brain volume by MRI
Cerebellar volume
Time frame: at term equivalent age (38 to 41 weeks' postmenstrual age)
Cerebellar volume by MRI
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
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
11 secondary outcomes
Fat mass
Time frame: at study endpoint (36 weeks' postmenstrual age or discharge)
Weight
Time frame: at 2 years' corrected age
Height
Time frame: at 2 years' corrected age
Low Bayley-III cognitive score
Time frame: At 2 years' corrected age
Low Bayley-III motor score
Time frame: At 2 years' corrected age
Bayley-III language score
Time frame: At 2 years' corrected age
Bayley-III language score
Time frame: At 2 years' corrected age
Spacial working memory
Time frame: at 2 years' corrected age
Behavioral inhibition
Time frame: at 2 years' corrected age
Executive function
Time frame: at 2 years' corrected age
Behavioral difficulties
Time frame: at 2 years' corrected age
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2026.
- Derived from this study: PubMed 42734908Belfort MB, Ahtam B, Bell KA, Berger P, Cherkerzian S, Ellard D, Foster L, Fusch C, Gagoski B, Grant PE, Kuncham M, Pepin H, Solti M, Steele T, Woodward L, Inder T. Individually Targeted Human Milk Fortification: A Randomized Clinical Trial. JAMA Pediatr. 2026 Sep 14:e264220. doi: 10.1001/jamapediatrics.2026.4220. Online ahead of print.
- Derived from this study: PubMed 33836708Belfort MB, Woodward LJ, Cherkerzian S, Pepin H, Ellard D, Steele T, Fusch C, Grant PE, Inder TE. Targeting human milk fortification to improve very preterm infant growth and brain development: study protocol for Nourish, a single-center randomized, controlled clinical trial. BMC Pediatr. 2021 Apr 9;21(1):167. doi: 10.1186/s12887-021-02635-x.
- Individual participant dataSharing planned: No. 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.
Related trials for Preterm Birth
Not yet recruiting
nCPAP-NAVA-Backup Versus Standard nCPAP for Severe Apnea in Preterm Infants ≤28 Weeks
Apnea of Prematurity
Recruiting
Study of the Influence of Intraperitoneal Insufflation of CO2 by Laparoscopy on the Short-term Evolution of Premature Infants With Ulcerative Necrotizing Enterocolitis
Preterm Birth, Enterocolitis, Necrotizing
Recruiting
Comparing Surfactant Administration Through Supraglottic Airway and Thin Catheter for Preterm Infants
Surfactant, Respiratory Distress Syndrome (Neonatal)
RecruitingObservational study
Multidimensional Dynamic Early Warning System for Neonatal Necrotizing Enterocolitis: A Multicenter Clinical Study
NEC - Necrotizing Enterocolitis
Recruiting
Optimization of Saturation Targets And Resuscitation Trial (OptiSTART)
Premature Infants, Bronchopulmonary Dysplasia
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.
Mandy B Belfort, MD, MPH principal investigator
Brigham and Women's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Individually targeted fortification in people with Preterm Birth and Breast Milk Expression, run by Brigham and Women's Hospital 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 4 inclusion and 12 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: under way, not looking for participants, as of the sponsor's last update on 15 Jun 2026. 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?
This study is still under way. Results are not available in the source record yet.
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?
Weight (time frame: at study endpoint (36 weeks' postmenstrual age or discharge)). The study lists 7 primary outcomes in all. 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 NCT03977259, which also lists 2 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 15 Jun 2026.