Early Protein Supplementation in Extremely Preterm Infants Fed Human Milk

NCT04325308 | Active Not Recruiting Results DMC

• 2 other identifiers: 300005089K23HD102554
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

The central hypothesis of this clinical trial is that, in extremely preterm infants, protein-enriched human milk diets compared to usual human milk diets during the first 2 weeks after birth increase fat-free mass (FFM)-for-age Z scores and promote maturation of the gut microbiome at term corrected age.

Conditions

Prematurity; Extreme; Feeding Disorder Neonatal; Breast Milk Expression; Growth Failure; Microbial Colonization

Outcome Measures

Primary Outcomes (1)

• Fat-free Mass(FFM)-For-age Z-score

  Estimated by air displacement plethysmography. FFM measurements were converted into Z-scores using updated, sex-specific reference curves of body composition in preterm infants (Norris et al, 2019). A Z-score of 0 represents the population mean. Z-score values closer to 0 represent a better outcome. No relevant thresholds have been defined.

  36 weeks or hospital discharge, up to 120 days following birth, whichever is longer

Secondary Outcomes (13)

• Fat Mass(FM)-For-age Z-score

  36 weeks or hospital discharge, up to 120 days following birth, whichever is longer

• Body Fat(BF)-For-age Z-score

  36 weeks or hospital discharge, up to 120 days following birth, whichever is longer

• Anthropometric Measurements

  Birth to 36 weeks postmenstrual age or hospital discharge (whichever occurred first)

• Growth Rate

  Birth to 36 weeks postmenstrual age or hospital discharge (whichever occurred first)

• Number of Participants With Postnatal Growth Failure

  36 weeks or hospital discharge (whichever occurred first)

Other Outcomes (2)

• Changes in Intestinal Microbiome

  Birth to 36 weeks postmenstrual age

• Cognitive Outcomes

  2 years of corrected age

Study Arms (2)

Protein-enriched human milk diet

EXPERIMENTAL

Infants in this group will receive protein-enriched expressed human milk or donor human milk during the first 2 weeks after birth.

Procedure: Protein-enriched human milk diet

Usual human milk diet

ACTIVE COMPARATOR

Infants in this group will receive either expressed human milk or donor human milk during the first 2 weeks after birth.

Procedure: Usual human milk diet

Interventions

Protein-enriched human milk diet PROCEDURE

1.2 g of human-based protein will be added to each 100 ml of human milk administered

Protein-enriched human milk diet

Usual human milk diet PROCEDURE

Human-based protein will not be added to the human milk administered.

Usual human milk diet

Eligibility Criteria

• Age: 1 Day - 4 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Gestational age ≤ 28 weeks of gestation
• Postnatal age \< 96 hours

You may not qualify if:

• Congenital malformations
• Chromosomal anomalies
• Terminal illness needing to limit or withhold support

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Related Publications (2)

• Tucker MJ, Jeffcoat SH, Argent T, Travers CP, Salas AA. Severity of Bronchopulmonary Dysplasia in Infants Born Extremely Preterm and Randomized to Early Human Milk Fortification with a Donor Milk-Derived Fortifier for 2 Weeks. J Pediatr. 2025 Dec;287:114750. doi: 10.1016/j.jpeds.2025.114750. Epub 2025 Jul 24.

  PMID: 40714049 RESULT

• Salas AA, Gunawan E, Nguyen K, Reeves A, Argent V, Finck A, Carlo WA. Early Human Milk Fortification in Infants Born Extremely Preterm: A Randomized Trial. Pediatrics. 2023 Sep 1;152(3):e2023061603. doi: 10.1542/peds.2023-061603.

  PMID: 37551512 RESULT

MeSH Terms

Conditions

Premature Birth; Breast Milk Expression; Failure to Thrive; Communicable Diseases

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Breast Feeding; Feeding Behavior; Behavior; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Infections; Disease Attributes; Pathologic Processes

Results Point of Contact

• Title: Ariel Salas
• Organization: University of Alabama at Birmingham

asalas@uab.edu

2059344680

Study Officials

• Ariel Salas, MD, MSPH

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Caregivers and primary outcome evaluators will be masked. Nutrition room staff not involved in patient care will be responsible for determining participant allocation to one of the supplementation groups by opening sequentially numbered sealed envelopes, dispensing feeding syringes with the allocated human milk diet (protein-enriched or usual), and masking caregivers administering the assigned dietary intervention.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 25, 2020
• First Posted: March 27, 2020
• Study Start: August 13, 2020
• Primary Completion: January 2, 2023
• Study Completion (Estimated): September 30, 2026
• Last Updated: September 23, 2025
• Results First Posted: March 13, 2024

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)