Intranasal Human Milk for Intraventricular Hemorrhage
Intranasal Human Milk for Intraventricular Hemorrhage
Intraventricular hemorrhage (IVH) is a leading cause of brain injury in infants born before
 term. Severe IVH, which occurs nearly exclusively in very preterm infants (born before 32
 weeks gestation) who are already at risk of neurodevelopmental delays and cerebral palsy at
 baseline, results in a ~5 times higher risk of death or moderate-severe neurodevelopmental
 impairment, as well as short-term morbidities in the neonatal intensive care unit (NICU).
 Infants with grade I and II IVH, although less severe than the higher grades of IVH, also
 have a higher risk of death or moderate to severe neurodevelopmental impairment compared to
 infants with a normal head ultrasound. Outcomes are worsened by the fact that the brains of
 these preterm infants are not fully developed, so the progenitor cells that would later
 differentiate and mature are damaged, resulting in hypomyelination and gray matter loss that
 are associated with poor neurodevelopmental outcomes. There is no available therapy to treat
 the IVH or resultant brain injury, other than symptomatic management for resultant
 post-hemorrhagic hydrocephalus with lumbar punctures and temporary or permanent shunts, which
 have significant risks on their own.

 This is a phase I trial to determine whether fresh intranasal human milk (HM) can be safely
 delivered as stem cell therapy to preterm IVH patients within a 3-hour window from HM
 expression and to identify signals which would indicate whether intranasal HM stimulates the
 repair of damaged brain tissue. Outcomes will be compared to HM fed historical IVH controls.
 Recruitment will take place in tertiary care NICUs in Toronto, which care for the highest
 proportion of very preterm infants with IVH in Canada. These NICUs have already adopted a
 common protocolized approach to manage severe IVH and post-hemorrhagic hydrocephalus with
 intensive monitoring, early symptomatic management, and detailed prospectively collected IVH
 data.
Inclusion Criteria:

 1. Preterm infants (<33 weeks gestation at birth, stratified < and ≥28 weeks) with any
 grade IVH/intraparenchymal hemorrhage/infarction on head ultrasound in the first 10 days of
 life. Diagnostic criteria will be based on the Papile definitions as used by the study
 sites/Toronto Centre for Neonatal Health for PHVD management, outlined in the document
 "Intraventricular Hemorrhage and Measurements of Lateral Ventricular Size from Head
 Ultrasound"

 Exclusion Criteria:

 1. Disorders associated with neurodevelopmental delays or impairment (i.e. Trisomy 21)

 2. Moribund/critically ill infant or known lethal diagnosis with plans by medical team to
 redirect care

 3. Choanal atresia or anomalies that would not allow intranasal treatment

 4. Surgical condition (e.g. esophageal atresia) for which team feels intranasal HM is
 contraindicated

 5. Enrolled in other intervention trials in which primary target is neurodevelopmental
 outcome

 6. Parent with lactation contraindication(s) (i.e. HIV) or parent who declines lactation
 initiation

 7. Lactating parent unable to provide fresh HM: unable/unwilling to pump at study site or
 unable to have fresh HM delivered by designee at least once/day for 3 days within 3
 hours of pumping AND located (in hospital or home) >30km from study sites (for courier
 services)