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  • Clinical Research Article
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Subcortical brain volumes in neonatal hypoxic–ischemic encephalopathy

Pediatric Research volume 94, pages 1797–1803 (2023)Cite this article

Abstract

Background

Despite treatment with therapeutic hypothermia, hypoxic–ischemic encephalopathy (HIE) is associated with adverse developmental outcomes, suggesting the involvement of subcortical structures including the thalamus and basal ganglia, which may be vulnerable to perinatal asphyxia, particularly during the acute period. The aims were: (1) to examine subcortical macrostructure in neonates with HIE compared to age- and sex-matched healthy neonates within the first week of life; (2) to determine whether subcortical brain volumes are associated with HIE severity.

Methods

Neonates (n = 56; HIE: n = 28; Healthy newborns from the Developing Human Connectome Project: n = 28) were scanned with MRI within the first week of life. Subcortical volumes were automatically extracted from T1-weighted images. General linear models assessed between-group differences in subcortical volumes, adjusting for sex, gestational age, postmenstrual age, and total cerebral volumes. Within-group analyses evaluated the association between subcortical volumes and HIE severity.

Results

Neonates with HIE had smaller bilateral thalamic, basal ganglia and right hippocampal and cerebellar volumes compared to controls (all, p < 0.02). Within the HIE group, mild HIE severity was associated with smaller volumes of the left and right basal ganglia (both, p < 0.007) and the left hippocampus and thalamus (both, p < 0.04).

Conclusions

Findings suggest that, despite advances in neonatal care, HIE is associated with significant alterations in subcortical brain macrostructure.

Impact

  • Compared to their healthy counterparts, infants with HIE demonstrate significant alterations in subcortical brain macrostructure on MRI acquired as early as 4 days after birth.

  • Smaller subcortical volumes impacting sensory and motor regions, including the thalamus, basal ganglia, and cerebellum, were seen in infants with HIE.

  • Mild and moderate HIE were associated with smaller subcortical volumes.

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Fig. 1: Segmented T1-weighted images comparing HIE and control subjects.
Fig. 2: Subcortical macrostructural differences in mean volumes between participants with HIE compared to healthy newborns.

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Data availability

The data supporting this study’s findings are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank the NICU families who participated in this study.

Funding

This study was financially supported by the Whaley and Harding Fellowship from the Children’s Health Foundation, Canada First Research Excellence Fund (BrainsCAN), and the Molly Towell Perinatal Research Foundation.

Author information

Authors and Affiliations

  1. Neuroscience program, Western University, London, ON, Canada

    Lilian M. N. Kebaya, Sandrine de Ribaupierre, Michael T. Jurkiewicz & Emma G. Duerden

  2. Division of Neonatal-Perinatal Medicine, Department of Paediatrics, London Health Sciences Centre, London, ON, Canada

    Lilian M. N. Kebaya, Paula Camila Mayorga, Paige Meyerink, Kathryn Foglton, Talal Altamimi & Soume Bhattacharya

  3. Applied Psychology, Faculty of Education, Western University, London, ON, Canada

    Bhavya Kapoor, Emily S. Nichols & Emma G. Duerden

  4. Western Institute for Neuroscience, Western University, London, ON, Canada

    Bhavya Kapoor, Emily S. Nichols, Sandrine de Ribaupierre, Michael T. Jurkiewicz & Emma G. Duerden

  5. Division of Neonatal Intensive Care, Department of Pediatrics, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia

    Talal Altamimi

  6. Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada

    Sandrine de Ribaupierre & Michael T. Jurkiewicz

  7. Children’s Health Research Institute, London, ON, Canada

    Sandrine de Ribaupierre & Emma G. Duerden

  8. Department of Medical Imaging, London Health Sciences Centre, London, ON, Canada

    Leandro Tristao & Michael T. Jurkiewicz

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Contributions

L.M.N.K., B.K., P.C.M., P.M., K.F., T.A., E.S.N., S.B., S.d.R., L.T., M.J., and E.G.D. were involved in the study design, database variable creation, and data acquisition design and execution of the data analytic strategy and reviewed and/or revised the final version of the manuscript. L.M.N.K., B.K., and E.G.D. contributed to the execution of the data analytic strategy, analyzed the data, and wrote the initial draft of the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

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Correspondence to Lilian M. N. Kebaya.

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Kebaya, L.M.N., Kapoor, B., Mayorga, P.C. et al. Subcortical brain volumes in neonatal hypoxic–ischemic encephalopathy. Pediatr Res 94, 1797–1803 (2023). https://doi.org/10.1038/s41390-023-02695-y

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