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Brain Volumetric Changes in Children Without Cerebral Palsy Aged 6-8 Years who were Cooled for Perinatal Asphyxial Encephalopathy

Presented at the Neonatal Society 2017 Summer Meeting (programme).

Lee-Kelland R1, Brooks J1, Tonks J1, Jary S1, Thai J1, Cowan F1, Thoresen M1,2, Chakkarapani E1

1 Neonatal Neuroscience, University of Bristol, UK
2 University of Oslo, Oslo, Norway

Background: Therapeutic hypothermia (TH), is standard care for children following perinatal asphyxial encephalopathy (PAE) and reduces the risk of death and cerebral palsy (CP) (1). Even in the absence of CP we found children with PAE to have lower full scale IQ and co-ordination difficulties at 6-8 years compared to age matched controls (2). Subcortical grey matter is very sensitive to hypoxic injury at birth (3). We hypothesise that children aged 6-8 years without CP will have reduced total brain and subcortical grey matter volumes compared to controls and that brain volumes would be associated with cognitive/motor scores.

Methods: Ethical approval was obtained to assess 28 children aged 6-8 years who received TH at St Michaelís Hospital, Bristol and did not develop CP and 20 control children, matched by age, sex and social class. Psychologists, blinded to case/control status, assessed cognition using the WISC-IV. Motor outcomes were assessed using the Movement-ABC-2 by a paediatrician. Total brain volume was calculated using FSLís FAST4 tool and analysis of subcortical volumes (hippocampus, basal ganglia and thalamus) using FIRST5 done by a blinded researcher.

Results: Of the 17/23 case and 17/20 control children who completed the MRI protocol with scans of sufficient quality, the case group had significantly lower median (IQR) total brain (1.49 litres (1.37-1.67) vs 1.61 litres (1.52-1.68), p=0.045), hippocampal (6199mm3 (4995-7178) vs 7294mm3 (6874-7873), p=0.007) and thalamic volumes (14001mm3 (12610-15603) vs 15788mm3 (15097-16706), p=0.011) compared to control children. Median (IQR) hippocampal volumes corrected for total brain volume (7) remained significantly lower in the cases (0.055mm3 (0.0048-0.0059) vs 0.006mm3 (0.0055-0.0064), p=0.02) and correlated significantly with WISC-IV full scale IQ in cases. (r2 =0.39. p=0.008).

Conclusion: Total brain and subcortical structures are reduced in volume in children with PAE without CP compared to age matched controls. Hippocampal volume corrected for total brain volume correlates with full scale IQ and may be a contributing factor for the cognitive impairments.

Corresponding author:

1. Jacobs et al 2013
2. Lee-Kelland et al Spring Neonatal Society 2017
3. Rutherford MRI of the Neonatal Brain ISBN 0 7020 2534 8 2002
4. Zhang et al IEEE Trans Med Image 2001
5. Patenaude et al NeuroImage 2011
6. Mathalon Neuroimage 1993

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