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In the trials, a substantial proportion of newborns who underwent therapeutic hypothermia (TH) had an adverse outcome after hypoxic-ischaemic encephalopathy (HIE). Cooled babies were noted to have fewer cerebral lesions on MRI but when present lesions were predictive of adverse outcome. We investigate the predictive value of cerebral MRI in babies who undergo cooling in the clinical setting outside of the clinical trials in a prospective UK cohort. Of 75 babies recruited from four centres, neurodevelopment was available for 69 (92%) with 29% (20/69) being abnormal. The unfavourable MRI group (n = 22) had significantly lower motor (p < 0.001), language (p < 0.001) and cognition (p < 0.001) scores on Bayley-III assessment, compared to the favourable MRI group (n = 47). On multiple regression there was a significant relationship between basal ganglia and thalami abnormality and motor (p = 0.002), cognition (p = 0.011) and language (p = 0.013) outcomes. Half of the babies who had an MRI predictive of adverse outcome (11/22) had highest grade cerebral palsy. Cerebral MRI had 95% sensitivity, 94% specificity, 91% PPV and 98% NPV in predicting neurodevelopment. In this clinical cohort, fewer children had adverse neurodevelopment after TH compared to the TH trials. However, half the children who had an MRI predictive of adverse ND outcome had the most severe form of cerebral palsy. In this cohort, cerebral MRI was found to be highly predictive of neurodevelopmental outcome. • In this cohort, conventional cerebral MRI is highly predictive of neurodevelopmental outcome. • 73% of babies with cerebral MRI predictive of adverse outcome developed cerebral palsy. • Conventional cerebral MRI provides useful prognostic information for counselling families. [ABSTRACT FROM AUTHOR]

Objective: To examine the effect of therapeutic hypothermia on MR biomarkers and neurodevelopmental outcomes in babies with mild hypoxic-ischaemic encephalopathy (HIE).Design: Non-randomised cohort study.Setting: Eight tertiary neonatal units in the UK and the USA.Patients: 47 babies with mild HIE on NICHD neurological examination performed within 6 hours after birth.Interventions: Whole-body cooling for 72 hours (n=32) or usual care (n=15; of these 5 were cooled for <12 hours).Main Outcome Measures: MRI and MR spectroscopy (MRS) within 2 weeks after birth, and a neurodevelopmental outcome assessment at 2 years.Results: The baseline characteristics in both groups were similar except for lower 10 min Apgar scores (p=0.02) in the cooled babies. Despite this, the mean (SD) thalamic NAA/Cr (1.4 (0.1) vs 1.6 (0.2); p<0.001) and NAA/Cho (0.67 (0.08) vs 0.89 (0.11); p<0.001) ratios from MRS were significantly higher in the cooled group. Cooled babies had lower white matter injury scores than non-cooled babies (p=0.02). Four (27%) non-cooled babies with mild HIE developed seizures after 6 hours of age, while none of the cooled babies developed seizures (p=0.008). Neurodevelopmental outcomes at 2 years were available in 40 (85%) of the babies. Adverse outcomes were seen in 2 (14.3%) non-cooled babies, and none of the cooled babies (p=0.09).Conclusions: Therapeutic hypothermia may have a neuroprotective effect in babies with mild HIE, as demonstrated by improved MRS biomarkers and reduced white matter injury on MRI. This may warrant further evaluation in adequately powered randomised controlled trials. [ABSTRACT FROM AUTHOR]

Aim: Servo-controlled therapeutic hypothermia is a routine therapy for babies with hypoxic-ischaemic encephalopathy in the neonatal unit and is delivered in designated cooling centres. It is increasingly being used during neonatal transport in the UK to deliver this therapy in a timelier manner for babies not born in a cooling centre. Prior to the implementation of this treatment, passive cooling alone was used in transport. Comparison of passive and servo-controlled cooling during neonatal transfers with reference to: (i) the proportion of babies in the therapeutic range (33-34°C) at three time points during the transport mission (arrival of the team at the referring unit, departure of the team from the referring unit and at the completion of transport); (ii) the proportion of babies overcooled at any point once the transport team was present (<33°C); and (iii) duration of phases of the transfer to evaluate the impact of active cooling on how long it takes to undertake transfer.Methods: This was a retrospective observational study comparing babies with passive and servo-controlled hypothermia (January 2015 to May 2016) following introduction of the servo-controlled cooling mattress.Results: A total of 48 patients were treated with hypothermia in transit (29 passive, 19 servo-controlled). The median gestational age (GA) was 40 weeks (interquartile range: 39-41) and mean birthweight (BW) 3420 g (standard deviation 600 g); there was no differences in GA, BW and clinical characteristics between the groups. There was a statistically significant difference in the temperature at the end of the transport, where 94% (n = 18) of babies who received servo-controlled cooling were in the target temperature in comparison with only 65% (n = 19) of the passive cooling group babies (P = 0.045). In addition, none of the babies in the servo-controlled group were warm (>34°C) at the end of the transfer. Babies who underwent servo-controlled cooling are more likely to maintain a target temperature (33-34°C) (17 (89%) vs. 17 (58%), P = 0.021); in particular, there is less overcooling (<33°C) in this group (2 (10%) vs. 15 (51%), P = 0.004). Total mission time was not significantly different.Conclusion: The use of servo-controlled cooling devices during neonatal transport improves the ability to maintain the baby's temperature within the target range (33-34°C) with less overcooling. [ABSTRACT FROM AUTHOR]

Objective: Screening criteria for neonatal encephalopathy remain a complex combination of subjective and objective criteria. We examine the utility of universal cord blood gas testing and mandatory encephalopathy evaluation for infants with pH ≤7.10 on umbilical cord arterial blood gas (cABG) as a single screening measure for timely identification of moderate/severe encephalopathy.Design, Setting, Patients: Infants born at a single centre between 2008 and 2015, who were ≥36 weeks, had no congenital anomalies and had a cABG pH ≤7.10 were identified for a retrospective cohort study. Maternal/perinatal and patient factors were collected.Results: 27 028 infants were born during the study period; 412 met all inclusion criteria. Of those, 35/85 infants with pH <7.00 and 34/327 infants with pH between 7.00 and 7.10 had moderate/severe encephalopathy. Encephalopathy was identified on the basis of pH and examination alone (no other perinatal criteria present) in 5/35 and 13/34 infants in the two pH groups, respectively.A cABG pH threshold of ≤7.10 was associated with a sensitivity of 74.2% and a specificity of 98.7% for detection of moderate/severe encephalopathy. Based on these data, 25 infants with cABG pH between 7.00 and 7.10 will need to be screened to identify one neonate with moderate/severe encephalopathy, who might have otherwise been missed using conventional screening, a 15% increase in appropriate selection and treatment over current methods.Conclusion: Universal cord blood gas screening with a pH threshold ≤7.10 and mandatory encephalopathy examination results in greater detection of infants with moderate/severe encephalopathy and timely initiation of therapeutic hypothermia. [ABSTRACT FROM AUTHOR]

Background: The 2007 Cochrane review of therapeutic hypothermia for neonatal encephalopathy (NE) indicates a significant reduction in adverse outcome. UK National Institute for Clinical Excellence guidelines are awaited. Objective: To benchmark current opinion and practice to inform future strategies for optimal knowledge transfer for therapeutic hypothermia. Methods: A web based questionnaire (30 sections related to opinion and practice of management of NE) sent to the clinical leads of Level I, II and III neonatal units throughout the UK in November/December 2007. Results: One hundred and twenty-five (out of 195) UK neonatal units responded (response rate 66%). Ten percent, 37.5% and 51.5% responses were from level I, II and III units respectively. Twenty eight percent of all units provided therapeutic hypothermia locally (52% of level III units), however 80% of responders would offer therapeutic hypothermia if there was the facility. Overall, 57% of responders considered therapeutic hypothermia effective or very effective – similar for all unit levels; 43% considered more data are required. Regional availability of therapeutic hypothermia exists in 55% of units and 41% of units offer transfer to a regional centre for therapeutic hypothermia. Conclusion: In the UK in 2007, access to therapeutic hypothermia was widespread although not universal. More than half of responders considered therapeutic hypothermia effective. Fifty-five percent of perinatal networks have the facility to offer therapeutic hypothermia. The involvement of national bodies may be necessary to ensure the adoption of therapeutic hypothermia according to defined protocols and standards; registration is important and will help ensure universal neurodevelopmental follow up. [ABSTRACT FROM AUTHOR]

Objective: Since 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., Design: Case-control study., Participants: 29 case children without CP, cooled in 2008-2010 and 20 age-matched, sex-matched and social class-matched term-born controls., Measures: Wechsler Intelligence Scales for Children, Fourth UK Edition, Movement Assessment Battery for Children, Second Edition (MABC-2) and Strengths and Difficulties Questionnaire., Results: Cases 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., Conclusions: School-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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)