Review

. 2024 Apr;95(5):1224-1236.

doi: 10.1038/s41390-023-02895-6. Epub 2023 Dec 19.

Neuroprotective therapies in the NICU in preterm infants: present and future (Neonatal Neurocritical Care Series)

Eleanor J Molloy^{1

2

3

4}, Mohamed El-Dib⁵, Janet Soul⁶, Sandra Juul⁷, Alistair J Gunn⁸, Manon Bender⁹, Fernando Gonzalez¹⁰, Cynthia Bearer^{11

12}, Yvonne Wu¹³, Nicola J Robertson^{14

15}, Mike Cotton¹⁶, Aoife Branagan^{17

18}, Tim Hurley¹⁷, Sidhartha Tan¹⁹, Abbot Laptook²⁰, Topun Austin²¹, Khorshid Mohammad²², Elizabeth Rogers²³, Karen Luyt^{24

25}, Pia Wintermark^{26

27}, Sonia Lomeli Bonifacio²⁸; Newborn Brain Society Guidelines and Publications Committee

Collaborators, Affiliations

Collaborators

Newborn Brain Society Guidelines and Publications Committee:
Sonia Lomeli Bonifacio, Pia Wintermark, Hany Aly, Vann Chau, Hannah Glass, Monica Lemmon, Courtney Wusthoff, Gabrielle deVeber, Andrea Pardo, Melisa Carrasco, James Boardman, Dawn Gano, Eric Peeples

Affiliations

¹ Paediatrics, Trinity College Dublin, Trinity Research in Childhood Centre (TRICC), Dublin, Ireland. Eleanor.molloy@tcd.ie.
² Children's Hospital Ireland (CHI) at Tallaght, Dublin, Ireland. Eleanor.molloy@tcd.ie.
³ Neonatology, CHI at Crumlin, Dublin, Ireland. Eleanor.molloy@tcd.ie.
⁴ Neonatology, Coombe Women's and Infants University Hospital, Dublin, Ireland. Eleanor.molloy@tcd.ie.
⁵ Department of Pediatrics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁶ Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
⁷ Department of Pediatrics, University of Washington, Seattle, WA, USA.
⁸ Departments of Physiology and Paediatrics, School of Medical Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand.
⁹ Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
¹⁰ Department of Neurology, Division of Child Neurology, University of California, San Francisco, California, USA.
¹¹ Division of Neonatology, Department of Pediatrics, Rainbow Babies & Children's Hospital, Cleveland, Ohio, USA.
¹² Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
¹³ Department of Neurology, University of California San Francisco, San Francisco, California, USA.
¹⁴ Institute for Women's Health, University College London, London, UK.
¹⁵ Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
¹⁶ Department of Pediatrics, Duke University, Durham, North Carolina, USA.
¹⁷ Paediatrics, Trinity College Dublin, Trinity Research in Childhood Centre (TRICC), Dublin, Ireland.
¹⁸ Neonatology, Coombe Women's and Infants University Hospital, Dublin, Ireland.
¹⁹ Wayne State University School of Medicine, Detroit, Michigan, USA.
²⁰ Department of Pediatrics, Women and Infants Hospital, Brown University, Providence, Rhode Island, USA.
²¹ Department of Paediatrics, University of Cambridge, Cambridge, UK.
²² Section of Neonatology, Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada.
²³ Department of Pediatrics, University of California, San Francisco Benioff Children's Hospital, San Francisco, California, USA.
²⁴ Translational Health Sciences, University of Bristol, Bristol, UK.
²⁵ Neonatology, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK.
²⁶ Division of Neonatology, Montreal Children's Hospital, Montreal, Quebec, Canada.
²⁷ McGill University Health Centre - Research Institute, Montreal, Quebec, Canada.
²⁸ Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA.

PMID: 38114609
PMCID: PMC11035150
DOI: 10.1038/s41390-023-02895-6

Review

Neuroprotective therapies in the NICU in preterm infants: present and future (Neonatal Neurocritical Care Series)

Eleanor J Molloy et al. Pediatr Res. 2024 Apr.

. 2024 Apr;95(5):1224-1236.

doi: 10.1038/s41390-023-02895-6. Epub 2023 Dec 19.

Authors

Collaborators

Newborn Brain Society Guidelines and Publications Committee:
Sonia Lomeli Bonifacio, Pia Wintermark, Hany Aly, Vann Chau, Hannah Glass, Monica Lemmon, Courtney Wusthoff, Gabrielle deVeber, Andrea Pardo, Melisa Carrasco, James Boardman, Dawn Gano, Eric Peeples

Affiliations

¹ Paediatrics, Trinity College Dublin, Trinity Research in Childhood Centre (TRICC), Dublin, Ireland. Eleanor.molloy@tcd.ie.
² Children's Hospital Ireland (CHI) at Tallaght, Dublin, Ireland. Eleanor.molloy@tcd.ie.
³ Neonatology, CHI at Crumlin, Dublin, Ireland. Eleanor.molloy@tcd.ie.
⁴ Neonatology, Coombe Women's and Infants University Hospital, Dublin, Ireland. Eleanor.molloy@tcd.ie.
⁵ Department of Pediatrics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁶ Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
⁷ Department of Pediatrics, University of Washington, Seattle, WA, USA.
⁸ Departments of Physiology and Paediatrics, School of Medical Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand.
⁹ Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
¹⁰ Department of Neurology, Division of Child Neurology, University of California, San Francisco, California, USA.
¹¹ Division of Neonatology, Department of Pediatrics, Rainbow Babies & Children's Hospital, Cleveland, Ohio, USA.
¹² Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
¹³ Department of Neurology, University of California San Francisco, San Francisco, California, USA.
¹⁴ Institute for Women's Health, University College London, London, UK.
¹⁵ Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
¹⁶ Department of Pediatrics, Duke University, Durham, North Carolina, USA.
¹⁷ Paediatrics, Trinity College Dublin, Trinity Research in Childhood Centre (TRICC), Dublin, Ireland.
¹⁸ Neonatology, Coombe Women's and Infants University Hospital, Dublin, Ireland.
¹⁹ Wayne State University School of Medicine, Detroit, Michigan, USA.
²⁰ Department of Pediatrics, Women and Infants Hospital, Brown University, Providence, Rhode Island, USA.
²¹ Department of Paediatrics, University of Cambridge, Cambridge, UK.
²² Section of Neonatology, Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada.
²³ Department of Pediatrics, University of California, San Francisco Benioff Children's Hospital, San Francisco, California, USA.
²⁴ Translational Health Sciences, University of Bristol, Bristol, UK.
²⁵ Neonatology, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK.
²⁶ Division of Neonatology, Montreal Children's Hospital, Montreal, Quebec, Canada.
²⁷ McGill University Health Centre - Research Institute, Montreal, Quebec, Canada.
²⁸ Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA.

PMID: 38114609
PMCID: PMC11035150
DOI: 10.1038/s41390-023-02895-6

Abstract

The survival of preterm infants has steadily improved thanks to advances in perinatal and neonatal intensive clinical care. The focus is now on finding ways to improve morbidities, especially neurological outcomes. Although antenatal steroids and magnesium for preterm infants have become routine therapies, studies have mainly demonstrated short-term benefits for antenatal steroid therapy but limited evidence for impact on long-term neurodevelopmental outcomes. Further advances in neuroprotective and neurorestorative therapies, improved neuromonitoring modalities to optimize recruitment in trials, and improved biomarkers to assess the response to treatment are essential. Among the most promising agents, multipotential stem cells, immunomodulation, and anti-inflammatory therapies can improve neural outcomes in preclinical studies and are the subject of considerable ongoing research. In the meantime, bundles of care protecting and nurturing the brain in the neonatal intensive care unit and beyond should be widely implemented in an effort to limit injury and promote neuroplasticity. IMPACT: With improved survival of preterm infants due to improved antenatal and neonatal care, our focus must now be to improve long-term neurological and neurodevelopmental outcomes. This review details the multifactorial pathogenesis of preterm brain injury and neuroprotective strategies in use at present, including antenatal care, seizure management and non-pharmacological NICU care. We discuss treatment strategies that are being evaluated as potential interventions to improve the neurodevelopmental outcomes of infants born prematurely.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

**Fig. 1. Brain injury in the premature infant can be caused by a variety of factors including infection and hypoxic injury.**
This can lead to diffuse damage, including cell loss via astrogliosis, oligodendrocyte arrest and impaired myelination. Intervention at each stage of injury and cell loss aims to prevent neurodevelopmental complications.

**Fig. 2**
Current and potential therapies to prevent and treat brain injury in the preterm infant.

**Fig. 3**
Example of using QI methodology, a driver diagram and smart aim to reduce IVH.

See this image and copyright information in PMC

References

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1. Chawanpaiboon S, et al. Global, regional, and national estimates of levels of preterm birth in 2014: a systematic review and modelling analysis. Lancet Glob. Health. 2019;7:e37–e46. doi: 10.1016/S2214-109X(18)30451-0. - DOI - PMC - PubMed
1. Sarda SP, Sarri G, Siffel C. Global prevalence of long-term neurodevelopmental impairment following extremely preterm birth: a systematic literature review. J. Int. Med. Res. 2021;49:3000605211028026. doi: 10.1177/03000605211028026. - DOI - PMC - PubMed
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1. GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392:1789–1858. doi: 10.1016/S0140-6736(18)32279-7. - DOI - PMC - PubMed

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Neuroprotective therapies in the NICU in preterm infants: present and future (Neonatal Neurocritical Care Series)

Collaborators

Affiliations

Neuroprotective therapies in the NICU in preterm infants: present and future (Neonatal Neurocritical Care Series)

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical