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

NCT03977259 | Active Not Recruiting

• 1 other identifier: 2019P000893
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 1

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.

Conditions

Preterm Birth; Breast Milk Expression; Nutrition Disorder, Infant; Brain Development Abnormality; Neurodevelopmental Disorders

Outcome Measures

Primary Outcomes (7)

• Weight

  Weight z-score

  at study endpoint (36 weeks' postmenstrual age or discharge)

• Length

  Length z-score

  at study endpoint (36 weeks' postmenstrual age or discharge)

• Fat free mass

  Fat free mass estimated with air displacement plethysmography (z-score)

  at study endpoint (36 weeks' postmenstrual age or discharge)

• Total brain volume

  Total brain volume by MRI

  at term equivalent age (38 to 41 weeks' postmenstrual age)

• Cerebellar volume

  Cerebellar volume by MRI

  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

  at 2 years' corrected age

• Bayley-III motor score

  Scaled composite score (continuous), higher score indicates better performance, range of possible scores 46-154

  at 2 years' corrected age

Secondary Outcomes (11)

• Fat mass

  at study endpoint (36 weeks' postmenstrual age or discharge)

• Weight

  at 2 years' corrected age

• Height

  at 2 years' corrected age

• Low Bayley-III cognitive score

  At 2 years' corrected age

• Low Bayley-III motor score

  At 2 years' corrected age

Study Arms (2)

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.

Other: Individually targeted fortification

Interventions

Individually targeted fortification 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.

Individually targeted fortification

Eligibility Criteria

• Age: 1 Day - 21 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• 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.

  PMID: 33836708 DERIVED

MeSH Terms

Conditions

Premature Birth; Breast Milk Expression; Infant Nutrition Disorders; Neurodevelopmental Disorders

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Breast Feeding; Feeding Behavior; Behavior; Nutrition Disorders; Nutritional and Metabolic Diseases; Mental Disorders

Study Officials

• Mandy B Belfort, MD, MPH

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Parents, clinical, and research staff apart from the study milk technician will be unaware of the treatment group.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Attending physician

Study Record Dates

• First Submitted: June 5, 2019
• First Posted: June 6, 2019
• Study Start: January 31, 2020
• Primary Completion: May 6, 2025
• Study Completion (Estimated): August 31, 2027
• Last Updated: June 17, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)