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

Multisensory Early Oral Administration of Human Milk in Preterm Infants to Attenuate Early Life Toxic Stress on Epigenetic Modifications and Dysbiosis: Randomized Controlled Trial Pilot Study

The aims of this pilot are to determine the feasibility and acceptability of the Multisensory early oral administration of human milk (M-MILK) intervention, recruitment, retention, and obtain data for sample size estimation. This study will advance nursing science and practice because it will inform our R01 RCT to examine the efficacy of M-MILK to attenuate adverse effects of early life toxic stress in preterm infants.

Study Overview

• Status: Completed
• Conditions: Stress; Infant Development
• Intervention / Treatment: Other: Multisensory Early Oral Administration of Human Milk (M-MILK)

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Loyola University Chicago

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• born between 22 to 34 weeks gestational age and receiving mother's own milk and/or donor milk.

Exclusion Criteria:

• receiving only formula, oral cavity defects, gastrointestinal defects, chromosomal abnormalities, severe cardiac defects that require surgery, or intraventricular hemorrhage grade III or IV

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: M-MILK; Infants in the M-MILK group will receive the M-MILK intervention in addition to standard of care.	Other: Multisensory Early Oral Administration of Human Milk (M-MILK); M-MILK is implemented starting on day 3 of life, after every hands-on care, during the beginning of a full gavage feeding. 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 nurses or parents.
No Intervention: Control; Infants in the control group will receive standard of care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of Intervention	The count of participants who receive M-MILK in at least 50% of their scheduled M-MILK administrations. MILK will be considered feasible if M-MILK is implemented by nurses or parents after every hands-on care and during the beginning of a full gavage feeding at least 50% of the time.	At the time of discharge from NICU, which is typically 10 to 16 weeks from birth.
Acceptability of Intervention	The percentage of parents who rate the intervention as very positive, slightly positive, or acceptable on a 5-point Likert scale.	At the time of discharge from NICU, which is typically 10 to 16 weeks from birth.
Retention	Retention will be described by the number of post-discharge follow-up surveys completed.	2 months corrected age
The Scarf Sign Cluster of the Neurobehavioral Assessment of the Preterm Infants Score	The Neurobehavioral Assessment of the Preterm Infants (NAPI, 73 items, 32-37 weeks PMA): cluster score for scarf sign ranges from 0-100, where higher scores indicate better neurodevelopmental performance.	At the time of discharge from NICU, which is typically 10 to 16 weeks from birth.
Variability in the Motor Development & Vigor Cluster of the Neurobehavioral Assessment of the Preterm Infants Score	The Neurobehavioral Assessment of the Preterm Infants (NAPI, 73 items, 32-37 weeks PMA): cluster score for motor development & vigor ranges from 0-100, where higher scores indicate better neurodevelopmental performance.	At the time of discharge from NICU, which is typically 10 to 16 weeks from birth.
Popliteal Angle Cluster of the Neurobehavioral Assessment of the Preterm Infants Score	The Neurobehavioral Assessment of the Preterm Infants (NAPI, 73 items, 32-37 weeks PMA): cluster score for popliteal angle ranges from 0-100, where higher scores indicate better neurodevelopmental performance.	At the time of discharge from NICU, which is typically 10 to 16 weeks from birth.
Alertness and Orientation Cluster of the Neurobehavioral Assessment of the Preterm Infants Score	The Neurobehavioral Assessment of the Preterm Infants (NAPI, 73 items, 32-37 weeks PMA): cluster score for alertness and orientation ranges from 0-100, where higher scores indicate better neurodevelopmental performance.	At the time of discharge from NICU, which is typically 10 to 16 weeks from birth.
Irritability Cluster of the Neurobehavioral Assessment of the Preterm Infants Score	The Neurobehavioral Assessment of the Preterm Infants (NAPI, 73 items, 32-37 weeks PMA): cluster score for irritability ranges from 0-100, where higher scores indicate better neurodevelopmental performance.	At the time of discharge from NICU, which is typically 10 to 16 weeks from birth.
Quality of Cry Cluster of the Neurobehavioral Assessment of the Preterm Infants Score	The Neurobehavioral Assessment of the Preterm Infants (NAPI, 73 items, 32-37 weeks PMA): cluster score for quality of cry ranges from 0-100, where higher scores indicate better neurodevelopmental performance.	At the time of discharge from NICU, which is typically 10 to 16 weeks from birth.
Percent Sleep Cluster of the Neurobehavioral Assessment of the Preterm Infants Score	The Neurobehavioral Assessment of the Preterm Infants (NAPI, 73 items, 32-37 weeks PMA): cluster score for percent sleep ranges from 0-100, where higher scores indicate better neurodevelopmental performance.	At the time of discharge from NICU, which is typically 10 to 16 weeks from birth.
Early Feeding Skill Assessment Score	EFS has 22 items (32-50 weeks PMA), summary scores, 5 subscales: respiratory regulation (range 5 - 15), oral-motor functioning (range 4 - 12), swallowing coordination (range 4 - 12), engagement (range 2 - 6), & physiologic stability (range 4 - 12), where higher scores indicate better oral feeding skill development. The total score is the sum of the subscales and ranges from 19-57.	At the time of discharge from NICU, which is typically 10 to 16 weeks from birth.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parent Stressor Scale: NICU Score	Scores range from 1 to 5, where higher scores indicate greater parental stress..	At the time of discharge from NICU, which is typically 10 to 16 weeks from birth.
Parent Discharge Readiness Score	Scores range from 44 to 308, where higher scores indicate more parental readiness for discharge.	At the time of discharge from NICU, which is typically 10 to 16 weeks from birth.
Breastmilk Pumping Rate	The percentage of mothers who report breastmilk pumping at discharge.	At the time of discharge from NICU, which is typically 10 to 16 weeks from birth.
Breastfeeding Rate	The percentage of mothers who report breastfeeding at discharge.	At the time of discharge from NICU, which is typically 10 to 16 weeks from birth.
Maternal Edinburgh Postnatal Depression Scale Score	Scores range from 0 to 30, where higher scores indicate greater depressive symptoms	At the time of discharge from NICU, which is typically 10 to 16 weeks from birth.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Variability in Gut Microbial Community Structure and Relative Abundance of SCFA- and Lactate- Producing Bacteria	Alpha diversity indices will be obtained. Differential abundance individual taxa will be obtained.	At the time of discharge from NICU, which is typically 10 to 16 weeks from birth.
Variability in DNA Methylation of NR3C1 Promoter	The percent DNAm at the NR3C1 promoters and at each CpG site will be quantified.	At the time of discharge from NICU, which is typically 10 to 16 weeks from birth.
Variability in DNA Methylation of HSD11B2 Promoter	The percent DNAm at the HSD11B2 promoters and at each CpG site will be quantified.	At the time of discharge from NICU, which is typically 10 to 16 weeks from birth.

Collaborators and Investigators

• Sponsor: Loyola University

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2023
• Primary Completion (Actual): October 23, 2024
• Study Completion (Actual): October 23, 2024

Study Registration Dates

• First Submitted: January 5, 2024
• First Submitted That Met QC Criteria: January 25, 2024
• First Posted (Actual): January 30, 2024

Study Record Updates

• Last Update Posted (Actual): January 8, 2026
• Last Update Submitted That Met QC Criteria: December 17, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: stress; preterm infants; gut microbiome; epigenetics; parent-infant relationship
• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Premature Birth
• Other Study ID Numbers: 217411

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No