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  • Systematic Review
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Early predictors of neurodevelopment after perinatal arterial ischemic stroke: a systematic review and meta-analysis

Pediatric Research volume 94, pages 20–33 (2023)Cite this article

Abstract

Background and aims

Perinatal arterial ischemic stroke (PAIS) often has lifelong neurodevelopmental consequences. We aimed to review early predictors (<4 months of age) of long-term outcome.

Methods

We carried out a systematic literature search (PubMed and Embase), and included articles describing term-born infants with PAIS that underwent a diagnostic procedure within four months of age, and had any reported outcome parameter ≥12 months of age. Two independent reviewers included studies and performed risk of bias analysis.

Results

We included 41 articles reporting on 1395 infants, whereof 1255 (90%) infants underwent follow-up at a median of 4 years. A meta-analysis was performed for the development of cerebral palsy (n = 23 studies); the best predictor was the qualitative or quantitative assessment of the corticospinal tracts on MRI, followed by standardized motor assessments. For long-term cognitive functioning, bedside techniques including (a)EEG and NIRS might be valuable. Injury to the optic radiation on DTI correctly predicted visual field defects. No predictors could be identified for behavior, language, and post-neonatal epilepsy.

Conclusion

Corticospinal tract assessment on MRI and standardized motor assessments are best to predict cerebral palsy after PAIS. Future research should be focused on improving outcome prediction for non-motor outcomes.

Impact

  • We present a systematic review of early predictors for various long-term outcome categories after perinatal arterial ischemic stroke (PAIS), including a meta-analysis for the outcome unilateral spastic cerebral palsy.

  • Corticospinal tract assessment on MRI and standardized motor assessments are best to predict cerebral palsy after PAIS, while bedside techniques such as (a)EEG and NIRS might improve cognitive outcome prediction.

  • Future research should be focused on improving outcome prediction for non-motor outcomes.

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Fig. 1: Meta-analysis of predictors of long-term motor outcome after PAIS.
Fig. 2: Predictors of outcome (except MRI) that were not included in the meta-analysis.
Fig. 3: MRI predictors of outcome that were not included in the meta-analysis.

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Data availability

Template data collection forms can be found in the protocol on Prospero. Data extracted from included studies and data used for analysis can be made available upon request with the corresponding author.

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Funding

This work was supported by the European Society for Pediatric Research (ESPR). The funder had no role in the study design, data collection and analysis, preparation of the manuscript or decision to publish. The authors have no further conflicts of interest to declare.

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Authors and Affiliations

  1. Department of Neonatology, University Medical Center Utrecht Brain Center and Wilhelmina Children’s Hospital, Utrecht University, Utrecht, The Netherlands

    Lisanne M. Baak, Niek E. van der Aa, Annemijn A. E. Verhagen, Jeroen Dudink, Floris Groenendaal, Manon J. N. L. Benders & Nienke Wagenaar

  2. Department for Developmental Origins of Disease, University Medical Center Utrecht Brain Center and Wilhelmina Children’s Hospital, Utrecht University, Utrecht, The Netherlands

    Cora H. A. Nijboer

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  1. Lisanne M. Baak
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Contributions

L.M.B. designed the protocol, performed the article search, and the statistical analyses, and wrote the original draft. L.M.B. and A.A.E.V. selected articles, extracted data and performed risk of bias analysis, with NEA as a third reviewer in case of discrepancies. NEA, F.G., J.D., C.H.A.N., M.J.N.L.B., and N.W. aided in design, conceptualization, and supervision. All authors reviewed and edited the paper and confirm that they had full access to all the data in the study and accept responsibility to submit for publication.

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Correspondence to Nienke Wagenaar.

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Baak, L.M., van der Aa, N.E., Verhagen, A.A.E. et al. Early predictors of neurodevelopment after perinatal arterial ischemic stroke: a systematic review and meta-analysis. Pediatr Res 94, 20–33 (2023). https://doi.org/10.1038/s41390-022-02433-w

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