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

NCT ID: NCT03977259

Last Updated: 2025-06-17

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 130 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-31
• Study Completion Date: 2027-08-31

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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

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.

Group Type: EXPERIMENTAL

Individually targeted fortification

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: OTHER

Eligibility 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

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 21 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Mandy Brown Belfort, MD MPH

Attending physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mandy B Belfort, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

Brigham and Women's Hospital

Boston, Massachusetts, United States

Countries

United States

References

Belfort 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.

Reference Type: DERIVED

PMID: 33836708 (View on PubMed)

Other Identifiers

2019P000893

Identifier Type: -

Identifier Source: org_study_id