Intranasal Fresh Mother's Own Milk to Prevent Intraventricular Hemorrhage in Extremely Preterm Infants

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.

Inclusion Criteria: 1. Gestational age ≤29+0 weeks based on the best obstetric estimate, with first-trimester ultrasound preferred. 2. Inborn at Women's Hospital or St. Boniface Hospital, Winnipeg, Manitoba, Canada. 3. Written informed consent obtained from a parent or legal guardian; antenatal consent may be obtained when preterm delivery is anticipated. 4. 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. 5. Enrollment within 72 hours of life. Exclusion Criteria: 1. Major congenital brain malformation, including holoprosencephaly, lissencephaly, schizencephaly, severe primary hydrocephalus, large arachnoid cyst, or other space-occupying lesion. 2. 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. 3. Trisomy 13, Trisomy 18, or another severe chromosomal/genetic disorder. 4. Acute surgical condition requiring immediate intervention, such as esophageal atresia with tracheoesophageal fistula. 5. Life-limiting condition, including comfort-care designation, anticipated survival \