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Cerebrovascular autoregulation and preterm brain injury: a systematic review and meta-analysis

Pediatric Research (2025)Cite this article

Abstract

Background

Preterm neonates are vulnerable to impaired cerebrovascular autoregulation (CAR), with a risk of developing cerebral injury (intraventricular hemorrhage or periventricular leukomalacia). In this meta-analysis, we evaluate the association between the degree of CAR and cerebral injury in preterm neonates, using various CAR assessment techniques mainly based on near-infrared spectroscopy.

Methods

We systematically searched PubMed and EMBASE between 01-05-2023 and 31-01-2024. We included original articles published between 2000-2023, reporting CAR and cerebral injury in preterm neonates. The study was registered in PROSPERO (ID: 427323). We assessed the standardized mean difference in degree of CAR in groups with and without cerebral injury, with a subgroup analysis of CAR measurement techniques.

Results

Seventeen articles were included, encompassing 742 patients. The overall standardized mean difference of 0.59 (95%CI 0.30, 0.88) indicates more impaired CAR in neonates with cerebral injury. Time-___domain analysis produced the least heterogeneous and most significant difference of 0.61 (95%CI 0.24, 0.98). Limitations include differences in measurement techniques and a lack of randomized controlled trials.

Conclusion

This meta-analysis showed an association between CAR and cerebral injury, highlighting the clinical relevance of CAR assessment in preterm neonates. Future randomized studies using standardized measurement techniques should assess the feasibility of CAR-guided hemodynamic management.

Impact

  • Cerebral injury and adverse neurological outcomes are prevalent in preterm neonates.

  • Historically, immature cerebrovascular autoregulation was thought to be one of the main causes of cerebral injury in this patient population.

  • This is the first study to systematically review and synthetize robust evidence on the relation between cerebrovascular autoregulation and preterm brain injury.

  • This meta-analysis further adds to the existing literature by comparing different cerebrovascular autoregulation measurement techniques.

  • The findings can help to standardize cerebrovascular autoregulation assessment and implement it in clinical practice using large, randomized trials.

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Fig. 1
Fig. 2: Forest plot, overview of studies included in the meta-analysis.
Fig. 3: Forest plot, subgroup analysis grouped by cerebrovascular autoregulation (CAR) measurement techniques.

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Data availability

All data and analyses as generated with RevMan are included in the published article.

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Acknowledgements

We thank all authors of the included studies, especially those who contributed additional data from their published articles upon request. Authors CLB and BEL were supported by the Junior Scientific Masterclass Groningen MD-PhD programme (MD-PhD 21-36, and MD-PhD 23-17) during the execution of this study. The other authors did not receive any funding. The study was registered in PROSPERO (ID: 427323).

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Authors and Affiliations

  1. Department of Neonatology, Beatrix Children’s Hospital, University Medical Center Groningen, Groningen, The Netherlands

    Celina L. Brunsch, Bineta E. Lahr & Elisabeth M. W. Kooi

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  1. Celina L. Brunsch
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  2. Bineta E. Lahr
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  3. Elisabeth M. W. Kooi
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Contributions

Celina L. Brunsch conceptualized and designed the study, conducted data acquisition, analysis and interpretation, drafted the manuscript and approves the final version to be published. Bineta E. Lahr assisted with data acquisition and interpretation, critically reviewed and revised the manuscript and approves the final version to be published. Dr Elisabeth M.W. Kooi supervised the conception and design, data acquisition and analysis, contributed substantially to the interpretation of the findings, critically reviewed and revised the manuscript and approves the final version to be published.

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Correspondence to Celina L. Brunsch.

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Brunsch, C.L., Lahr, B.E. & Kooi, E.M.W. Cerebrovascular autoregulation and preterm brain injury: a systematic review and meta-analysis. Pediatr Res (2025). https://doi.org/10.1038/s41390-025-04087-w

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