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Feasibility of intranasal human milk as stem cell therapy in preterm infants with intraventricular hemorrhage

Journal of Perinatology (2024)Cite this article

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Abstract

Objective

Intraventricular hemorrhage (IVH) is a common cause of preterm brain injury. Fresh parent’s own milk (POM) contains pluripotent stem cells (SCs) that produce neuronal cells in-vitro. The permeable neonatal blood brain barrier potentially allows SC delivery. We performed the first prospective trial (clinicaltrials.gov NCT04225286) of feasibility of intranasal POM (IPOM) in preterm infants with IVH and described SC content of POM samples.

Study design

37 Infants (mean gestation 27.7 ± 2.6 weeks, birthweight 1030 ± 320 g) with IVH (35.1% grade IV) were recruited from two tertiary Toronto NICUs. IPOM was given ideally twice daily until 28 days of age. Tolerance and adverse reactions were collected and 162 administering providers surveyed.

Results

There were no major adverse reactions. Provider surveys suggested acceptability, although potential provider and subject stress requires further study. Milk cell analysis suggests wide variability between parents.

Conclusions

This phase 1 study demonstrated IPOM was tolerated and feasible in preterm infants.

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Fig. 1: Study enrollment flowchart.

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Data availability

Data generated or analyzed during this study are included in this article and “in progress” publications. Further enquiries can be directed to the corresponding author.

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Acknowledgements

We are grateful to the families who participated in the study, as well as NICU staff whose support made this study possible during a pandemic. Thank you to Svetlana Madjunkova, Denis Gallagher and Peter Szaraz of the CReATe Fertility Center for their assistance in stem cell analysis protocols.

Funding

Funding for this project was obtained through The New Frontiers in Research Fund – Exploration Grant 2018, Canadian Tri-Agencies (grant ID NFRFE-2018-01610).

Author information

Authors and Affiliations

  1. Division of Neonatology, The Hospital for Sick Children/University of Toronto, Toronto, ON, Canada

    Rebecca Hoban, Alessia Gallipoli & Diane Wilson

  2. Division of Neonatology, University of Washington, Seattle, WA, USA

    Rebecca Hoban

  3. Ted Rogers Computational Program, Peter Munk Cardiac Centre, University Health Network, Toronto, ON, Canada

    Marisa Signorile

  4. CReATe Fertility Centre, Toronto, ON, Canada

    Poonam Mander, Andree Gauthier-Fisher & Clifford Librach

  5. Department of Obstetrics and Gynecology, IMS and Physiology, University of Toronto, Toronto, ON, Canada

    Clifford Librach

  6. Sunnybrook Research Institute, Toronto, ON, Canada

    Clifford Librach

  7. Department of Paediatrics, Izaak Walton Killam Hospital, Halifax, NS, Canada

    Sharon Unger

Authors
  1. Rebecca Hoban
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  2. Alessia Gallipoli
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  3. Marisa Signorile
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  4. Poonam Mander
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  5. Andree Gauthier-Fisher
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  6. Clifford Librach
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  7. Diane Wilson
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  8. Sharon Unger
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Contributions

RH was the PI on the grant and project and the primary clinician involved. She contributed to project conception and design, data acquisition and interpretation, and drafting the manuscript. AG contributed to the acquisition and interpretation of data and drafting the manuscript and was involved clinically at bedside. MS contributed to the analysis and interpretation of data and editing/reviewing the manuscript. PM, AGF, and CL contributed to the design of the project (stem cell analysis and perspectives), the acquisition, analysis, and interpretation of data, and drafting (AGF) and reviewing/editing (PM, CL) the manuscript. DW contributed to the design of the project and reviewing/editing the manuscript and was involved clinically at bedside. SU contributed to project design, data acquisition, and reviewing/editing the manuscript and was involved clinically at bedside. All authors approve of the final version to be published and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Rebecca Hoban.

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Competing interests

The authors have no conflicts of interest to declare related to the study. RH is currently on the scientific advisory board for Medela, USA (was not at the time of the study).

Ethics

Study approval statement: This study protocol was reviewed and approved by the Ontario provincial research ethics board Clinical Trials Ontario (CTO), Project ID 1911. Consent to participate statement Written informed consent was obtained from the guardian(s) of eligible participants prior to participation in the study.

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Hoban, R., Gallipoli, A., Signorile, M. et al. Feasibility of intranasal human milk as stem cell therapy in preterm infants with intraventricular hemorrhage. J Perinatol (2024). https://doi.org/10.1038/s41372-024-01982-8

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  • DOI: https://doi.org/10.1038/s41372-024-01982-8

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