ObjectiveSince therapeutic hypothermia became standard care for neonatal hypoxic–ischaemic encephalopathy (HIE), even fewer infants die or have disability at 18-month assessment than in the clinical trials. However, longer term follow-up of apparently unimpaired children is lacking. We investigated the cognitive, motor and behavioural performances of survivors without cerebral palsy (CP) cooled for HIE, in comparison with matched non-HIE control children at 6–8 years.DesignCase–control study.Participants29 case children without CP, cooled in 2008–2010 and 20 age-matched, sex-matched and social class-matched term-born controls.MeasuresWechsler Intelligence Scales for Children, Fourth UK Edition, Movement Assessment Battery for Children, Second Edition (MABC-2) and Strengths and Difficulties Questionnaire.ResultsCases compared with controls had significantly lower mean (SD) full-scale IQ (91 [10.37]vs105[13.41]; mean difference (MD): −13.62, 95% CI −20.53 to –6.71) and total MABC-2 scores (7.9 [3.26]vs10.2[2.86]; MD: −2.12, 95% CI −3.93 to –0.3). Mean differences were significant between cases and controls for verbal comprehension (−8.8, 95% CI –14.25 to –3.34), perceptual reasoning (−13.9, 95% CI–20.78 to –7.09), working memory (−8.2, 95% CI–16.29 to –0.17), processing speed (−11.6, 95% CI–20.69 to –2.47), aiming and catching (−1.6, 95% CI–3.26 to –0.10) and manual dexterity (−2.8, 95% CI–4.64 to –0.85). The case group reported significantly higher median (IQR) total (12 [6.5–13.5] vs 6 [2.25–10], p=0.005) and emotional behavioural difficulties (2 [1–4.5] vs 0.5 [0–2.75], p=0.03) and more case children needed extra support in school (34%vs5%, p=0.02) than the control group.ConclusionsSchool-age children without CP cooled for HIE still have reduced cognitive and motor performance and more emotional difficulties than their peers, strongly supporting the need for school-age assessments.

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Aim: To investigate whether motor performance in school-age children without cerebral palsy (CP), cooled for neonatal encephalopathy, is associated with perinatal factors and 18month developmental scores and to explore relationships between school-age motor and cognitive performance.Methods: Motor and cognitive performance was assessed in 29 previously cooled children at six to eight years using the Movement Assessment Battery for Children-2 (MABC-2) and the Wechsler Intelligence Scale for Children (WISC-IV). Associations between MABC-2 scores less than/equal (≤) 15th centile and perinatal factors, social/family background, 18month Bayley-III scores and WISC-IV scores were explored.Results: Eleven of the 29 (38%) children had MABC-2 scores ≤15th centile including 7 (24%) ≤5th centile. No significant perinatal or socio-economic risk factors were identified. Motor scores <85 at 18 months failed to identify children with MABC-2 scores ≤15th centile. MABC-2 scores ≤15th centile were associated with lower Full Scale IQ (p = 0.045), Working Memory (p = 0.03) and Perceptual Reasoning (p = 0.005) scores at six to eight years and receiving greater support in school (p = 0.01).Conclusion: A third of cooled children without CP had MABC-2 scores indicating motor impairment at school age that was not identified at 18 months by Bayley-III. Most children with low MABC scores needed support at school. Sub-optimal MABC-2 scores indicate need for detailed school-age cognitive evaluation.

Objectives: Dorsal-stream functions are vulnerable to early brain injury associated with neonatal encephalopathy (NE) following perinatal asphyxia, even in children not developing cerebral palsy (CP). Since therapeutic hypothermia (TH) became the standard treatment for NE, the incidence of CP is reduced but the impact on dorsal-stream functions is unknown. We aimed to compare dorsal-stream functions in TH-treated survivors of NE, without CP, with those of matched controls. Methods: We administered tests of dorsal-stream function to 29 case children aged 6-to-8 years treated with TH for NE and without CP, and 20 age, sex and social class matched controls. We used the Conner's Continuous Performance Test (CPT) 2 nd Edition to assess attentiveness, based upon Hit Reaction Time (HRT) percentile score and HRT standard error percentile, the CPT HRT block change measure to assess sustained attention and the NEPSY-II block construction and arrows tests to assess visuo-spatial performance and mental rotation. Results: Case children performed significantly worse than controls on measures of attention and visuo-spatial function. Conclusions: Children given TH treatment for NE can have subtle attention difficulties with slower reaction times and reduced visuo-spatial processing. These findings illustrate the continued vulnerability of dorsal-stream functions following NE despite the use of TH.

Andrew Whitelaw (AW) performed the original literature search, extracted data, and conducted the original Cochrane Review (Whitelaw 2001a). Yolanda Montagne, former Cochrane Neonatal Trials Search Coordinator, updated the search in 2009 and AW screened articles for potential inclusion. For this update, Richard Lee-Kelland (RLK) updated the literature search, text, and analyses, and included a new analysis of outcomes 1.6 and 1.7. AW reviewed the updated search, text, and analyses.

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.

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Introduction: Diffusion MRI allows non-invasive assessment of white matter connectivity in typical development and of changes due to brain injury or pathology. Probabilistic white matter atlases allow diffusion metrics to be measured in specific white matter pathways, and are a critical component in spatial normalisation for group analysis. However, given the known developmental changes in white matter it may be sub-optimal to use an adult template when assessing data acquired from children. Methods:By averaging subject-specific fibre bundles from 28 children aged from 6 to 8 years, we created an age-specific probabilistic white matter atlas for 12 major white matter tracts.Using both the newly developed and Johns Hopkins adult atlases, we compared the atlas to subject-specific fibre bundles in two independent validation cohorts, assessing accuracy in terms of volumetric overlap and measured diffusion metrics.Results: Our age-specific atlas gave better overall performance than the adult atlas, achieving higher volumetric overlap with subject-specific fibre tracking and higher correlation of FA measurements with those measured from subject-specific fibre bundles. Specifically, estimates of FA values for cortico-spinal tract, uncinate fasciculus, forceps minor, cingulate gyrus part of the cingulum and anterior thalamic radiation were all significantly more accurate when estimated with an age-specific atlas. Discussion:The age-specific atlas allows delineation of white matter tracts in children aged 6-8 years, without the need for tractography, more accurately than when normalising to an adult atlas. To our knowledge, this is the first publicly available probabilistic atlas of white matter tracts for this age group.