Multisensory Early Oral Administration of Human Milk (M-MILK) for Very Preterm Infants

NCT07216664 | Recruiting DMC

• 1 other identifier: 218601
• Study Type: interventional
• Target: 125
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this clinical trial is to learn if the multisensory early oral administration of human milk (M-MILK) intervention helps infants who are born younger than 32 weeks gestational age (very preterm infants). The main question that this clinical trial aims to answer is: Does M-MILK improve stress regulation, support optimal neurodevelopment, and promote competent oral feeding skills in very preterm infants? Researchers will compare M-MILK to the standard of care to see if M-MILK helps very preterm infants. Specifically, researchers will compare the differences in:

• Cortisol levels
• DNA methylation of the two stress related genes (NR3C1 and HSD11B2)
• Neurodevelopment
• Oral feeding skills Participants in the M-MILK group will receive standard of care plus M-MILK intervention, which starts on day 3 of life and continues until they begin their oral feeding. M-MILK will be provided by clinical research nurses, during the day shift, up to 4 times a day. Participants in the standard of care group will continue to receive their usual care.

Conditions

Infant, Premature, Diseases

Outcome Measures

Primary Outcomes (2)

• Oral feeding Skills: EFS assessment total score at PO Initiation

  We will evaluate oral feeding skills using the Early Feeding Skills Assessment (EFS) at oral feeding (PO) initiation. The EFS provides a summary score for each of the 5 subscale (respiratory regulation, oral-motor functioning, swallowing coordination, engagement, and physiologic stability), as well as a total summary score. Higher EFS summary scores indicate more competent oral feeding skills.

  Up to 12 weeks after birth.

• Oral Feeding Skills: EFS assessment total score at 36 Weeks PMA

  We will evaluate oral feeding skills using the Early Feeding Skills Assessment (EFS) at 36 weeks post-menstrual age (PMA). The EFS provides a summary score for each of the 5 subscale (respiratory regulation, oral-motor functioning, swallowing coordination, engagement, and physiologic stability), as well as a total summary score. Higher EFS summary scores indicate more competent oral feeding skills.

  36 weeks postmenstrual age.

Secondary Outcomes (19)

• Stress Regulation: Salivary Cortisol at PO Initiation

  Up to 12 weeks after birth.

• Stress Regulation: Salivary Cortisol at 36 Weeks PMA

  At 36 weeks postmenstrual age.

• Stress Regulation: Buccal Cell DNAm of NR3C1 Exon 1F Promoter at PO Initiation

  Up to 12 weeks after birth.

• Stress Regulation: Buccal Cell DNAm of NR3C1 Exon 1F Promoter at 36 Weeks PMA

  At 36 weeks postmenstrual age.

• Stress Regulation: Buccal Cell DNAm of HSD11B2 Promoter at PO Initiation

  Up to 12 weeks after birth.

Other Outcomes (19)

• Oral Feeding Skills: EFS assessment score for Respiratory Regulation at PO Initiation

  Up to 12 weeks after birth.

• Oral Feeding Skills: EFS assessment score for Oral-motor Functioning at PO Initiation

  Up to 12 weeks after birth.

• Oral Feeding Skills: EFS assessment score for Swallowing Coordination at PO Initiation

  Up to 12 weeks after birth.

Study Arms (2)

M-MILK Group

EXPERIMENTAL

Infants in the M-MILK group will receive M-MILK intervention and standard of care. M-MILK is implemented starting on day 3 of life, during the day shift, after every hands-on care, during the beginning of a full gavage feeding, and up to 4 times a day. Infants receive M-MILK in small droplets via a 1-ml syringe. M-MILK will cease upon oral feeding initiation. Infants will receive either mother's own milk or donor's milk based on availability. Infants may receive up to 1 mL of milk each time based on their cues and responses. The 1 mL volume intake is included as part of their oral caloric intake. M-MILK is provided by research nurses or parents.

Other: Multisensory early oral administration of human milk

Control Group

NO INTERVENTION

Infants in the Control group will receive standard of care.

Interventions

Multisensory early oral administration of human milk OTHER

M-MILK is implemented starting on day 3 of life, during the day shift, after every hands-on care, during the beginning of a full gavage feeding, and up to 4 times a day. Infants receive M-MILK in small droplets via a 1-ml syringe. M-MILK will cease upon oral feeding initiation. Infants will receive either mother's own milk or donor's milk based on availability. Infants may receive up to 1 mL of milk each time based on their cues and responses. The 1 mL volume intake is included as part of their oral caloric intake. M-MILK is provided by research nurses or parents.

Also known as: M-MILK

M-MILK Group

Eligibility Criteria

• Age: 23 Weeks - 32 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Born at ≤ 32 weeks gestational age.
• Receiving mother's own milk and/or donor human milk at the time of screening.

You may not qualify if:

• Receiving only formula.
• Gastrointestinal defects, i.e., cleft lip or cleft palate.
• Congenital cardiac defects requiring surgery.
• Necrotizing enterocolitis.
• Chromosomal abnormalities.

Sponsors & Collaborators

• Loyola University: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• Rush University Medical Center: collaborator

Study Sites (2)

Loyola University Chicago

Maywood, Illinois, 60153, United States

RECRUITING

Loyola University Medical Center

Maywood, Illinois, 60153, United States

RECRUITING

Related Publications (1)

• Griffith T, Janusek L, White-Traut R, Green SJ, Sachin A, Joyce C. Study Protocol for a Randomized Controlled Trial of Multisensory Early Oral Administration of Human Milk (M-MILK) for Very Preterm Infants: Enhancing Stress Regulation, Neurodevelopment, and Oral Feeding Skills. Biol Res Nurs. 2026 Jan 19:10998004261418708. doi: 10.1177/10998004261418708. Online ahead of print.

  PMID: 41554032 DERIVED

MeSH Terms

Conditions

Infant, Premature, Diseases

Condition Hierarchy (Ancestors)

Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Thao Griffith, PhD

  Loyola University Chicago

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Thao Griffith, PhD

CONTACT

464-220-9825; tgriffith1@luc.edu

Cara Joyce, PhD

CONTACT

464-220-9521; cjoyce6@luc.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2024
• First Posted: October 14, 2025
• Study Start: November 3, 2025
• Primary Completion (Estimated): May 31, 2030
• Study Completion (Estimated): May 31, 2031
• Last Updated: January 20, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)