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Outcomes after intranasal human milk therapy in preterm infants with intraventricular hemorrhage

Journal of Perinatology volume 45, pages 202–207 (2025)Cite this article

Subjects

Abstract

Objective

Intraventricular hemorrhage (IVH) is a common cause of brain injury in preterm infants. Fresh human milk (HM) contains stem cells (SCs) that could potentially be delivered via intranasal HM (IHM). In this IHM pilot study, we describe outcomes.

Study design

Infants <33 weeks gestation with IVH were given IHM until maximum 28 days of age. Short-term neurologic outcomes and follow-up testing were compared to historic HM-fed infants. Longitudinal outcomes were plotted using linear mixed models. Weighted G-computation quantified treatment effects. Propensity score models calculated inverse probability weights for IVH grade, gestational age, and sex.

Result

37 infants (35.1% grade 3-4 IVH) were compared to 191 historic controls (17.8% grade 3-4 IVH). Post-hemorrhagic ventricular dilatation was common (25.7% IHM patients). Most weighted outcomes, although not significant, favored IHM at 4-12 and 18 months corrected age.

Conclusion

This phase 1 study suggests powered trials of IHM for brain injury are needed.

Clinical Trial Registry Name

clinicaltrials.gov identifier NCT04225286

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Data availability

Relevant data generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author.

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Acknowledgements

We are grateful to the families who participated, as well as the bedside nursing, medical, and respiratory staff who made this study possible during the pandemic.

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, Toronto, ON, Canada

    Alessia Gallipoli, Amr El Shahed, Diane Wilson & Rebecca Hoban

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

    Sharon Unger

  3. University of Toronto, Toronto, ON, Canada

    Amr El Shahed

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

    Chun-Po Steve Fan & Marisa Signorile

  5. Division of Neonatology, Seattle Children’s Hospital, Seattle, WA, USA

    Rebecca Hoban

  6. University of Washington, Seattle, WA, USA

    Rebecca Hoban

Authors
  1. Alessia Gallipoli
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  2. Sharon Unger
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  3. Amr El Shahed
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  4. Chun-Po Steve Fan
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  5. Marisa Signorile
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  6. Diane Wilson
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  7. Rebecca Hoban
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Contributions

RH was responsible for conceptualization, funding acquisition, methodology, project administration, supervision, investigation, data collection, and writing (both original draft and review/editing). AG, a trainee at the time of the study, was responsible for data collection, data visualization, and writing (both original draft and review/editing). SU was responsible for funding acquisition, supervision, investigation, data collection, and writing (review/editing). AES and DW were responsible for funding acquisition, investigation, data collection, and writing (review/editing). SF and MS provided computing resources and software, statistical methodology and formal analysis, and writing (both original draft and review/editing).

Corresponding author

Correspondence to Rebecca Hoban.

Ethics declarations

Competing interests

The authors have no conflicts of interest relevant to this article to disclose. RH is currently on the clinical advisory board for Medela America (was not on the board during this study.)

Consent to participate statement

Written informed consent was obtained from the guardian of eligible participants prior to participation in the intervention portion of the study.

Ethics approval

This study protocol was reviewed and approved by Clinical Trials Ontario, project ID 1911.

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Gallipoli, A., Unger, S., El Shahed, A. et al. Outcomes after intranasal human milk therapy in preterm infants with intraventricular hemorrhage. J Perinatol 45, 202–207 (2025). https://doi.org/10.1038/s41372-024-02147-3

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