Intranasal Fresh Mother's Own Milk to Prevent Intraventricular Hemorrhage in Extremely Preterm Infants (iF-MOM-IVH)
Intranasal Fresh Mother's Own Milk (iF-MOM) for Prevention of Intraventricular Hemorrhage in Extremely Preterm Infants ≤29 Weeks' Gestational Age: A Prospective, Nonrandomized Interventional Study With Propensity Score-Weighted Historical Controls
Babies born very prematurely are at risk of intraventricular hemorrhage (IVH), which is bleeding in or around the fluid-filled spaces of the brain. Most IVH occurs during the first week after birth. Human colostrum and early breast milk contain growth factors, neurotrophic factors, immune-modulating substances, antioxidants, and other biologically active components that may have neuroprotective effects.
This study will evaluate whether giving very small amounts of a baby's own mother's fresh breast milk as nasal drops during the first 7 days of life may help prevent IVH in infants born at 29 weeks' gestation or earlier.
Approximately 67 eligible infants will be enrolled prospectively at Women's Hospital and St. Boniface Hospital in Winnipeg, Manitoba, Canada. At each scheduled study care session, fresh mother's own milk will be administered intranasally at 0.2 mL per nostril (0.4 mL total) before routine nursing care and, if tolerated and the infant remains clinically stable, repeated after care. Thus, a completed care session provides up to 0.8 mL. Study administration will be coordinated with 2-4 routine care sessions per day for 7 consecutive days, corresponding to a planned total daily volume of 1.6-3.2 mL.
The main study outcome is whether IVH of any grade is present on the routine cranial ultrasound performed at 4 to 7 days of life. Other outcomes include severe IVH, progression of IVH, post-hemorrhagic ventricular complications, mortality before hospital discharge, and the safety and tolerability of intranasal mother's own milk.
Outcomes in the prospectively treated infants will be compared with those of eligible infants previously cared for at the same neonatal intensive care units between 2020 and 2025. Statistical methods using propensity score weighting will be used to account for measured differences between the prospectively treated infants and the historical comparison group.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Intraventricular hemorrhage (IVH) remains an important complication of extreme prematurity and occurs predominantly during the first postnatal week. The immature germinal matrix vasculature, impaired cerebral autoregulation, hemodynamic instability, inflammation, oxidative stress, and other factors contribute to vulnerability to hemorrhage in extremely preterm infants.
Fresh colostrum and early mother's own milk contain multiple biologically active constituents with potential neuroprotective effects, including growth factors, neurotrophins, anti-inflammatory and immune-modulating mediators, antioxidants, and other bioactive components. Intranasal administration is being evaluated as a non-invasive route that may permit exposure of the central nervous system to milk-derived bioactive factors through proposed olfactory, trigeminal, perineural, and perivascular pathways.
This is a prospective, nonrandomized interventional study conducted at Women's Hospital and St. Boniface Hospital in Winnipeg, Manitoba, Canada. Eligible inborn infants at 29+0 weeks' gestation or less will be prospectively enrolled within 72 hours of birth. Enrolled infants will receive intranasal fresh mother's own milk during the first 7 days of life.
Fresh milk from the infant's own mother or birthing parent will be used. Milk used for study dosing will not be refrigerated or frozen before intranasal administration and will be used within 3 hours of expression. Each study dose consists of 0.2 mL administered into each nostril, for a total of 0.4 mL per dose. Doses will be administered 2 to 4 times daily for 7 consecutive days, coordinated with routine nursing care when possible. Clinical feeding and oral immune therapy needs will take priority over study dosing.
Infants will remain on continuous cardiorespiratory monitoring and pulse oximetry. Safety assessments will be performed during dosing and for at least 60 minutes after each administration. Study dosing may be delayed, withheld, or stopped if prespecified clinical instability or safety concerns occur.
The primary outcome is the presence of any IVH, Papile Grades I-IV, on cranial ultrasound performed at 4 to 7 days of life. Secondary outcomes include severe IVH, progression of IVH on subsequent imaging, post-hemorrhagic ventricular complications requiring intervention, all-cause mortality through hospital discharge, and safety and tolerability outcomes related to intranasal administration.
The study will enroll approximately 67 prospectively treated infants. Their outcomes will be compared with those of up to 188 historical controls admitted to the same two neonatal intensive care units between January 1, 2020 and December 31, 2025. Historical controls will meet the prespecified eligibility criteria and must have a documented cranial ultrasound at 4 to 7 days of life.
Because participants are not randomized to a concurrent control group, propensity scores will be estimated using prespecified maternal and neonatal characteristics. Stabilized inverse probability of treatment weighting and weighted regression methods will be used to reduce measured baseline imbalance between the prospectively treated infants and historical controls. The primary cranial ultrasound outcome will be assessed by a reviewer blinded to intervention versus historical-control status.
An optional mechanistic sub-study will permit storage and analysis of small leftover aliquots of study milk from Day 1 and Day 7, when sufficient milk remains after clinical and study dosing requirements are met. These samples will be used for approved analyses of selected naturally occurring milk components, including growth factors and neurotrophins.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Michael Narvey
- Phone Number: 204-899-6845
- Email: mnarvey@hsc.mb.ca
Study Contact Backup
- Name: Mohamed Habib
- Phone Number: 4319988002
- Email: mustchange84@gmail.com
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Gestational age ≤29+0 weeks based on the best obstetric estimate, with first-trimester ultrasound preferred.
- Inborn at Women's Hospital or St. Boniface Hospital, Winnipeg, Manitoba, Canada.
- Written informed consent obtained from a parent or legal guardian; antenatal consent may be obtained when preterm delivery is anticipated.
- Mother/birthing parent intends and is able to provide fresh own milk for study dosing; low initial milk volume is acceptable because of the small intranasal dosing requirements.
- Enrollment within 72 hours of life.
Exclusion Criteria:
- Major congenital brain malformation, including holoprosencephaly, lissencephaly, schizencephaly, severe primary hydrocephalus, large arachnoid cyst, or other space-occupying lesion.
- Airway or nasal anomaly precluding intranasal administration, including choanal atresia/stenosis, severe cleft palate/lip with nasal involvement, or Pierre Robin sequence with severe obstruction.
- Trisomy 13, Trisomy 18, or another severe chromosomal/genetic disorder.
- Acute surgical condition requiring immediate intervention, such as esophageal atresia with tracheoesophageal fistula.
- Life-limiting condition, including comfort-care designation, anticipated survival <72 hours, known lethal diagnosis such as bilateral renal agenesis or anencephaly, or severe birth asphyxia with anticipated poor neurologic outcome.
- Maternal contraindication to lactation, including HIV, or inability/unwillingness to provide fresh mother's own milk.
- Evidence of Grade III-IV intraventricular hemorrhage on cranial ultrasound before enrollment.
- Absence of fresh own-mother/birthing-parent milk for study dosing, including circumstances in which only donor or surrogate-provided milk is available.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: iF-MOM Intervention
Eligible extremely preterm infants born at ≤29+0 weeks' gestation will receive intranasal fresh mother's own milk (iF-MOM) in addition to standard neonatal intensive care.
The initial administration volume is 0.2 mL per nostril (0.4 mL total).
If tolerated without a clinically significant administration-related adverse event, the volume may be increased to 0.4 mL per nostril (0.8 mL total) at the discretion of the treating/study clinical team.
Intranasal administrations will occur 2-4 times daily, coordinated around routine nursing care, for 7 consecutive days.
|
Fresh breast milk from the infant's own mother/birthing parent will be administered intranasally.
The initial volume is 0.2 mL into each nostril (0.4 mL total per administration).
If tolerated, the volume may be increased to 0.4 mL into each nostril (0.8 mL total per administration).
Administration will occur 2-4 times daily for 7 consecutive days.
Milk used for study dosing will be fresh from expression, maintained at room temperature, never refrigerated or frozen before administration, and used within 3 hours of expression.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Incidence of Any-Grade Intraventricular Hemorrhage (Papile Grades I-IV)
Time Frame: 4 to 7 days of life
|
Presence of any intraventricular hemorrhage (IVH), Papile Grades I-IV, assessed on the standardized cranial ultrasound performed at 4-7 days of life.
|
4 to 7 days of life
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Incidence of Severe Intraventricular Hemorrhage (Papile Grades III-IV)
Time Frame: From the initial cranial ultrasound performed at 4-7 days of life through hospital discharge, up to 6 months of life
|
Presence of severe IVH, defined as Papile Grade III or IV, on the day 4-7 cranial ultrasound or subsequent clinically indicated cranial ultrasound imaging.
|
From the initial cranial ultrasound performed at 4-7 days of life through hospital discharge, up to 6 months of life
|
|
Progression of Intraventricular Hemorrhage
Time Frame: From the initial cranial ultrasound performed at 4-7 days of life through hospital discharge, up to 6 months of life
|
Worsening of IVH grade on repeat cranial ultrasound compared with the initial day 4-7 cranial ultrasound.
|
From the initial cranial ultrasound performed at 4-7 days of life through hospital discharge, up to 6 months of life
|
|
Post-Hemorrhagic Ventricular Dilatation Requiring Intervention
Time Frame: From the initial cranial ultrasound performed at 4-7 days of life through hospital discharge, up to 6 months of life
|
Development of post-hemorrhagic ventricular dilatation requiring clinical or neurosurgical intervention, including ventriculoperitoneal shunt when applicable.
|
From the initial cranial ultrasound performed at 4-7 days of life through hospital discharge, up to 6 months of life
|
|
All-Cause Mortality
Time Frame: From birth until death or hospital discharge, whichever occurs first, assessed up to 6 months of life
|
Death from any cause occurring before hospital discharge.
|
From birth until death or hospital discharge, whichever occurs first, assessed up to 6 months of life
|
|
Incidence and Severity of Adverse Events Associated With Intranasal iF-MOM Administration
Time Frame: During the 7-day intervention period
|
Adverse events occurring during or after iF-MOM administration will be recorded and classified as mild, moderate, severe, or serious according to the prespecified study safety criteria.
|
During the 7-day intervention period
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Michael Narvey, University of Manitoba
Publications and helpful links
General Publications
- Keller T, Korber F, Oberthuer A, Schafmeyer L, Mehler K, Kuhr K, Kribs A. Intranasal breast milk for premature infants with severe intraventricular hemorrhage-an observation. Eur J Pediatr. 2019 Feb;178(2):199-206. doi: 10.1007/s00431-018-3279-7. Epub 2018 Nov 1.
- Hoban R, Gallipoli A, Signorile M, Mander P, Gauthier-Fisher A, Librach C, Wilson D, Unger S. Feasibility of intranasal human milk as stem cell therapy in preterm infants with intraventricular hemorrhage. J Perinatol. 2024 Nov;44(11):1652-1657. doi: 10.1038/s41372-024-01982-8. Epub 2024 Apr 30.
- Nagy Z, Obeidat M, Mate V, Nagy R, Szanto E, Veres DS, Koi T, Hegyi P, Major GS, Garami M, Gasparics A, Te Pas AB, Szabo M. Occurrence and Time of Onset of Intraventricular Hemorrhage in Preterm Neonates: A Systematic Review and Meta-Analysis of Individual Patient Data. JAMA Pediatr. 2025 Feb 1;179(2):145-154. doi: 10.1001/jamapediatrics.2024.5998.
- Sonmez Demir G, Ozdemir OM, Turgut M, Pekal Y, Koyuncu E, Gungor O, Ergin H. Impact of Intranasal Administration of Fresh Breast Milk in Very Low Birth Weight Infants With Germinal Matrix-Intraventricular Hemorrhage. Cureus. 2025 Mar 11;17(3):e80416. doi: 10.7759/cureus.80416. eCollection 2025 Mar.
- Gallipoli A, Unger S, El Shahed A, Fan CS, Signorile M, Wilson D, Hoban R. Outcomes after intranasal human milk therapy in preterm infants with intraventricular hemorrhage. J Perinatol. 2025 Feb;45(2):202-207. doi: 10.1038/s41372-024-02147-3. Epub 2024 Oct 9.
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- iF-MOM-IVH
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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