Brain volumes and functional outcomes in children without cerebral palsy after therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy

Arthur P C Spencer; Richard Lee-Kelland; Jonathan C W Brooks; Sally Jary; James Tonks; Frances M Cowan; Marianne Thoresen; Ela Chakkarapani

doi:10.1111/dmcn.15369

Brain volumes and functional outcomes in children without cerebral palsy after therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy

Arthur P C Spencer, Richard Lee-Kelland, Jonathan C W Brooks, Sally Jary, James Tonks, Frances M Cowan, Marianne Thoresen, Ela Chakkarapani

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Abstract

AIM: To investigate whether brain volumes were reduced in children aged 6 to 8 years without cerebral palsy, who underwent therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy (patients), and matched controls, and to examine the relation between subcortical volumes and functional outcome.

METHOD: We measured regional brain volumes in 31 patients and 32 controls (median age 7 years and 7 years 2 months respectively) from T1-weighted magnetic resonance imaging (MRI). We assessed cognition using the Wechsler Intelligence Scales for Children, Fourth Edition and motor ability using the Movement Assessment Battery for Children, Second Edition (MABC-2).

RESULTS: Patients had lower volume of whole-brain grey matter, white matter, pallidi, hippocampi, and thalami than controls (false discovery rate-corrected p < 0.05). Differences in subcortical grey-matter volumes were not independent of total brain volume (TBV). In patients, hippocampal and thalamic volumes correlated with full-scale IQ (hippocampi, r = 0.477, p = 0.010; thalami, r = 0.452, p = 0.016) and MABC-2 total score (hippocampi, r = 0.526, p = 0.004; thalami, r = 0.505, p = 0.006) independent of age, sex, and TBV. No significant correlations were found in controls. In patients, cortical injury on neonatal MRI was associated with reduced volumes of hippocampi (p = 0.001), thalami (p = 0.002), grey matter (p = 0.015), and white matter (p = 0.013).

INTERPRETATION: Children who underwent therapeutic hypothermia have reduced whole-brain grey and white-matter volumes, with associations between hippocampal and thalamic volumes and functional outcomes.

Original language	English
Journal	Developmental Medicine and Child Neurology
Early online date	30 Jul 2022
DOIs	https://doi.org/10.1111/dmcn.15369
Publication status	E-pub ahead of print - 30 Jul 2022

Bibliographical note

Funding Information:
The Baily Thomas Charitable Fund (TRUST/VC/AC/SG4681‐7596), David Telling Charitable Trust, Sparks (05/BTL/01 and 14/BTL/01), and Moulton Foundation. A.P.C.S. is supported by the Wellcome Trust (WT220070/Z/20/Z). J.C.W.B. is supported by the UK Medical Research Council (MR/N026969/1).

Publisher Copyright:
© 2022 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.

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Spencer, A. P. C., Lee-Kelland, R., Brooks, J. C. W., Jary, S., Tonks, J., Cowan, F. M., Thoresen, M., & Chakkarapani, E. (2022). Brain volumes and functional outcomes in children without cerebral palsy after therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy. Developmental Medicine and Child Neurology. Advance online publication. https://doi.org/10.1111/dmcn.15369

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title = "Brain volumes and functional outcomes in children without cerebral palsy after therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy",

abstract = "AIM: To investigate whether brain volumes were reduced in children aged 6 to 8 years without cerebral palsy, who underwent therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy (patients), and matched controls, and to examine the relation between subcortical volumes and functional outcome.METHOD: We measured regional brain volumes in 31 patients and 32 controls (median age 7 years and 7 years 2 months respectively) from T1-weighted magnetic resonance imaging (MRI). We assessed cognition using the Wechsler Intelligence Scales for Children, Fourth Edition and motor ability using the Movement Assessment Battery for Children, Second Edition (MABC-2).RESULTS: Patients had lower volume of whole-brain grey matter, white matter, pallidi, hippocampi, and thalami than controls (false discovery rate-corrected p < 0.05). Differences in subcortical grey-matter volumes were not independent of total brain volume (TBV). In patients, hippocampal and thalamic volumes correlated with full-scale IQ (hippocampi, r = 0.477, p = 0.010; thalami, r = 0.452, p = 0.016) and MABC-2 total score (hippocampi, r = 0.526, p = 0.004; thalami, r = 0.505, p = 0.006) independent of age, sex, and TBV. No significant correlations were found in controls. In patients, cortical injury on neonatal MRI was associated with reduced volumes of hippocampi (p = 0.001), thalami (p = 0.002), grey matter (p = 0.015), and white matter (p = 0.013).INTERPRETATION: Children who underwent therapeutic hypothermia have reduced whole-brain grey and white-matter volumes, with associations between hippocampal and thalamic volumes and functional outcomes.",

author = "Spencer, {Arthur P C} and Richard Lee-Kelland and Brooks, {Jonathan C W} and Sally Jary and James Tonks and Cowan, {Frances M} and Marianne Thoresen and Ela Chakkarapani",

note = "Funding Information: The Baily Thomas Charitable Fund (TRUST/VC/AC/SG4681‐7596), David Telling Charitable Trust, Sparks (05/BTL/01 and 14/BTL/01), and Moulton Foundation. A.P.C.S. is supported by the Wellcome Trust (WT220070/Z/20/Z). J.C.W.B. is supported by the UK Medical Research Council (MR/N026969/1). Publisher Copyright: {\textcopyright} 2022 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.",

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TY - JOUR

T1 - Brain volumes and functional outcomes in children without cerebral palsy after therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy

AU - Spencer, Arthur P C

AU - Lee-Kelland, Richard

AU - Brooks, Jonathan C W

AU - Jary, Sally

AU - Tonks, James

AU - Cowan, Frances M

AU - Thoresen, Marianne

AU - Chakkarapani, Ela

N1 - Funding Information: The Baily Thomas Charitable Fund (TRUST/VC/AC/SG4681‐7596), David Telling Charitable Trust, Sparks (05/BTL/01 and 14/BTL/01), and Moulton Foundation. A.P.C.S. is supported by the Wellcome Trust (WT220070/Z/20/Z). J.C.W.B. is supported by the UK Medical Research Council (MR/N026969/1). Publisher Copyright: © 2022 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.

PY - 2022/7/30

Y1 - 2022/7/30

N2 - AIM: To investigate whether brain volumes were reduced in children aged 6 to 8 years without cerebral palsy, who underwent therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy (patients), and matched controls, and to examine the relation between subcortical volumes and functional outcome.METHOD: We measured regional brain volumes in 31 patients and 32 controls (median age 7 years and 7 years 2 months respectively) from T1-weighted magnetic resonance imaging (MRI). We assessed cognition using the Wechsler Intelligence Scales for Children, Fourth Edition and motor ability using the Movement Assessment Battery for Children, Second Edition (MABC-2).RESULTS: Patients had lower volume of whole-brain grey matter, white matter, pallidi, hippocampi, and thalami than controls (false discovery rate-corrected p < 0.05). Differences in subcortical grey-matter volumes were not independent of total brain volume (TBV). In patients, hippocampal and thalamic volumes correlated with full-scale IQ (hippocampi, r = 0.477, p = 0.010; thalami, r = 0.452, p = 0.016) and MABC-2 total score (hippocampi, r = 0.526, p = 0.004; thalami, r = 0.505, p = 0.006) independent of age, sex, and TBV. No significant correlations were found in controls. In patients, cortical injury on neonatal MRI was associated with reduced volumes of hippocampi (p = 0.001), thalami (p = 0.002), grey matter (p = 0.015), and white matter (p = 0.013).INTERPRETATION: Children who underwent therapeutic hypothermia have reduced whole-brain grey and white-matter volumes, with associations between hippocampal and thalamic volumes and functional outcomes.

AB - AIM: To investigate whether brain volumes were reduced in children aged 6 to 8 years without cerebral palsy, who underwent therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy (patients), and matched controls, and to examine the relation between subcortical volumes and functional outcome.METHOD: We measured regional brain volumes in 31 patients and 32 controls (median age 7 years and 7 years 2 months respectively) from T1-weighted magnetic resonance imaging (MRI). We assessed cognition using the Wechsler Intelligence Scales for Children, Fourth Edition and motor ability using the Movement Assessment Battery for Children, Second Edition (MABC-2).RESULTS: Patients had lower volume of whole-brain grey matter, white matter, pallidi, hippocampi, and thalami than controls (false discovery rate-corrected p < 0.05). Differences in subcortical grey-matter volumes were not independent of total brain volume (TBV). In patients, hippocampal and thalamic volumes correlated with full-scale IQ (hippocampi, r = 0.477, p = 0.010; thalami, r = 0.452, p = 0.016) and MABC-2 total score (hippocampi, r = 0.526, p = 0.004; thalami, r = 0.505, p = 0.006) independent of age, sex, and TBV. No significant correlations were found in controls. In patients, cortical injury on neonatal MRI was associated with reduced volumes of hippocampi (p = 0.001), thalami (p = 0.002), grey matter (p = 0.015), and white matter (p = 0.013).INTERPRETATION: Children who underwent therapeutic hypothermia have reduced whole-brain grey and white-matter volumes, with associations between hippocampal and thalamic volumes and functional outcomes.

U2 - 10.1111/dmcn.15369

DO - 10.1111/dmcn.15369

M3 - Article (Academic Journal)

C2 - 35907252

SN - 0012-1622

JO - Developmental Medicine and Child Neurology

JF - Developmental Medicine and Child Neurology

ER -

Brain volumes and functional outcomes in children without cerebral palsy after therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy

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