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  • Clinical Research Article
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Neurodevelopmental correlates of caudate volume in children born at risk of neonatal hypoglycaemia

Pediatric Research volume 93, pages 1634–1641 (2023)Cite this article

Abstract

Background

Neonatal hypoglycaemia can lead to brain damage and neurocognitive impairment. Neonatal hypoglycaemia is associated with smaller caudate volume in the mid-childhood. We investigated the relationship between neurodevelopmental outcomes and caudate volume and whether this relationship was influenced by neonatal hypoglycaemia.

Methods

Children born at risk of neonatal hypoglycaemia ≥36 weeks’ gestation who participated in a prospective cohort study underwent neurodevelopmental assessment (executive function, academic achievement, and emotional-behavioural regulation) and MRI at age 9–10 years. Neonatal hypoglycaemia was defined as at least one hypoglycaemic episode (blood glucose concentration <2.6 mmol/L or at least 10 min of interstitial glucose concentrations <2.6 mmol/L). Caudate volume was computed using FreeSurfer.

Results

There were 101 children with MRI and neurodevelopmental data available, of whom 70 had experienced neonatal hypoglycaemia. Smaller caudate volume was associated with greater parent-reported emotional and behavioural difficulties, and poorer prosocial behaviour. Caudate volume was significantly associated with visual memory only in children who had not experienced neonatal hypoglycaemia (interaction p = 0.03), but there were no other significant interactions between caudate volume and neonatal hypoglycaemia.

Conclusion

Smaller caudate volume is associated with emotional behaviour difficulties in the mid-childhood. Although neonatal hypoglycaemia is associated with smaller caudate volume, this appears not to contribute to clinically relevant neurodevelopmental deficits.

Impact

  • At 9–10 years of age, caudate volume was inversely associated with emotional-behavioural difficulties and positively associated with prosocial behaviour but was not related to executive function or educational achievement.

  • Previous studies have suggested that neonatal hypoglycaemia may contribute to smaller caudate volume but exposure to neonatal hypoglycaemia did not appear to influence the relationship between caudate volume and behaviour.

  • Among children not exposed to neonatal hypoglycaemia, caudate volume was also positively associated with visual memory, but no such association was detected among those exposed to neonatal hypoglycaemia.

  • Understanding early-life factors that affect caudate development may provide targets for improving behavioural function.

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Fig. 1: Interaction between neonatal hypoglycaemia and paired associate learning.

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Data availability

Published data are available to approved researchers under the data sharing arrangements provided by the Clinical Data Research Hub, based at the Liggins Institute, University of Auckland (https://wiki.auckland.ac.nz/researchhub). Metadata, along with instructions for data access, are available at the University of Auckland’s research data repository, Figshare (https://auckland.figshare.com). Data access requests are to be submitted to Data Access Committee via researchhub@auckland.ac.nz. Deidentified published data will be shared with researchers who provide a methodologically sound proposal and have appropriate ethical and institutional approval. Researchers must sign and adhere to the Data Access Agreement that includes a commitment to using the data only for the specified proposal, to refrain from any attempt to identify individual participants, to store data securely, and to destroy or return the data after completion of the project. The Clinical Data Research Hub reserves the right to charge a fee to cover the costs of making data available, if required.

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Acknowledgements

We are grateful to the children and families who participated in this study. We thank the staff of the Centre for Advanced Magnetic Resonance Imaging and Midland Radiology for MRI scanning and the Centre for eResearch for computing support. This research was supported by use of the Nectar Research Cloud, a collaborative Australian research platform supported by the NCRIS-funded Australian Research Data Commons (ARDC). We would like to thank the CHYLD steering group for their input.

Funding

Health Research Council of New Zealand (17/240); Neurological Foundation (1729PG), and Liggins Institute PhD scholarship (awarded to S.N.).

Author information

Authors and Affiliations

  1. Liggins Institute, University of Auckland, Auckland, New Zealand

    Eleanor Kennedy, Samson Nivins, Benjamin Thompson & Jane Harding

  2. Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden

    Samson Nivins

  3. School of Optometry and Vision Science, University of Waterloo, Waterloo, ON, Canada

    Benjamin Thompson

  4. Centre for Eye and Vision Research, 17W Science Park, Hong Kong, Hong Kong

    Benjamin Thompson

  5. Kidz First Neonatal Care, Counties Manukau Health, Auckland, New Zealand

    Christopher J. D. McKinlay

  6. Department of Paediatrics: Child and Youth Health, University of Auckland, Auckland, New Zealand

    Christopher J. D. McKinlay

  7. University of Auckland, Auckland, New Zealand

    Jane Harding, Christopher McKinlay, Jane Alsweiler, Gavin Brown, Gregory Gamble, Trecia Wouldes, Peter Keegan, Jason Turuwhenua, Jenny Rogers, Eleanor Kennedy, Rajesh Shah, Darren Dai, Samson Nivins, Jocelyn Ledger, Stephanie Macdonald, Alecia McNeill, Coila Bevan, Nataliia Burakevych, Robin May, Safayet Hossin, Grace McKnight, Rashedul Hasan & Jessica Wilson

  8. Victoria University Wellington, Wellington, New Zealand

    Deborah Harris

  9. University of Canterbury, Christchurch, New Zealand

    J. Geoffrey Chase, Jennifer Knopp & Tony Zhou

  10. University of Waterloo, Waterloo, ON, Canada

    Benjamin Thompson & Arijit Chakraborty

  11. Hospital for Sick Children, Toronto, ON, Canada

    Steven Miller

Authors
  1. Eleanor Kennedy
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  2. Samson Nivins
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  3. Benjamin Thompson
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  4. Christopher J. D. McKinlay
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  5. Jane Harding
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Consortia

for the CHYLD Study Team

  • Steering group

    • Jane Harding
    • , Christopher McKinlay
    • , Jane Alsweiler
    • , Gavin Brown
    • , Gregory Gamble
    • , Trecia Wouldes
    • , Peter Keegan
    • , Deborah Harris
    • , J. Geoffrey Chase
    •  & Benjamin Thompson

  • Other members of the CHYLD Mid-childhood Outcome Study team

    • Jason Turuwhenua
    • , Jenny Rogers
    • , Eleanor Kennedy
    • , Rajesh Shah
    • , Darren Dai
    • , Samson Nivins
    • , Jocelyn Ledger
    • , Stephanie Macdonald
    • , Alecia McNeill
    • , Coila Bevan
    • , Nataliia Burakevych
    • , Robin May
    • , Safayet Hossin
    • , Grace McKnight
    • , Rashedul Hasan
    • , Jessica Wilson
    • , Jennifer Knopp
    • , Arijit Chakraborty
    • , Tony Zhou
    •  & Steven Miller

Contributions

E.K.: conceptualization, formal analysis, resources, writing—original draft. S.N.: investigation, writing—review and editing. B.T.: funding acquisition, writing—review and editing. C.J.D.M.: conceptualization, funding acquisition, writing—review and editing. J.H.: conceptualization, supervision, funding acquisition, writing—review and editing.

Corresponding author

Correspondence to Jane Harding.

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Competing interests

The authors declare no competing interests.

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Parents or primary caregivers provided written informed consent and the child provided assent.

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Kennedy, E., Nivins, S., Thompson, B. et al. Neurodevelopmental correlates of caudate volume in children born at risk of neonatal hypoglycaemia. Pediatr Res 93, 1634–1641 (2023). https://doi.org/10.1038/s41390-022-02410-3

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  • DOI: https://doi.org/10.1038/s41390-022-02410-3

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