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Assessment of brain tissue injury after moderate hypothermia in neonates with hypoxic–ischaemic encephalopathy: a nested substudy of a randomised controlled trial
Open accessAbstract
BACKGROUND: Moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy might improve survival and neurological outcomes at up to 18 months of age, although complete neurological assessment at this age is difficult. To ascertain more precisely the effect of therapeutic hypothermia on neonatal cerebral injury, we assessed cerebral lesions on MRI scans of infants who participated in the Total Body Hypothermia for Neonatal Encephalopathy (TOBY) trial. METHODS: In the TOBY trial hypoxic-ischaemic encephalopathy was graded clinically according to the changes seen on amplitude integrated EEG, and infants were randomly assigned to intensive care with or without cooling by central telephone randomisation. The relation between allocation to hypothermia or normothermia and cerebral lesions was assessed by logistic regression with perinatal factors as covariates, and adjusted odds ratios (ORs) were calculated. The TOBY trial is registered, number ISRCTN 89547571. FINDINGS: 325 infants were recruited in the TOBY trial between 2002 and 2006. Images were available for analysis from 131 infants. Therapeutic hypothermia was associated with a reduction in lesions in the basal ganglia or thalamus (OR 0.36, 95% CI 0.15-0.84; p=0.02), white matter (0.30, 0.12-0.77; p=0.01), and abnormal posterior limb of the internal capsule (0.38, 0.17-0.85; p=0.02). Compared with non-cooled infants, cooled infants had fewer scans that were predictive of later neuromotor abnormalities (0.41, 0.18-0.91; p=0.03) and were more likely to have normal scans (2.81, 1.13-6.93; p=0.03). The accuracy of prediction by MRI of death or disability to 18 months of age was 0.84 (0.74-0.94) in the cooled group and 0.81 (0.71-0.91) in the non-cooled group. INTERPRETATION: Therapeutic hypothermia decreases brain tissue injury in infants with hypoxic-ischaemic encephalopathy. The predictive value of MRI for subsequent neurological impairment is not affected by therapeutic hypothermia. FUNDING: UK Medical Research Council; UK Department of Health.
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Cites
Bayley Scales of Infant Development
(2007) · Encyclopedia of Measurement and Statistics · doi:10.4135/9781412952644.n48 · Cited by 4,240
Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy
Shankaran, S., Laptook, A. R., Ehrenkranz, R. A., Tyson, J. E., McDonald, S. A., Donovan, E. F., Fanaroff, A. A., Poole, W. K., Wright, L. L., Higgins, R. D., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmcps050929 · Cited by 2,862
Cooling for newborns with hypoxic ischaemic encephalopathy
Jacobs, S. E., Berg, M., Hunt, R., Tarnow-Mordi, W. O., Inder, T. E., & Davis, P. G. (2013) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003311.pub3 · Cited by 2,328
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Self-citationModerate Hypothermia to Treat Perinatal Asphyxial Encephalopathy
Azzopardi, D. V., Strohm, B., Edwards, A. D., Dyet, L., Halliday, H. L., Juszczak, E., Kapellou, O., Levene, M., Marlow, N., Porter, E., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0900854 · Cited by 1,710
Self-citationValidation of a Model of Gross Motor Function for Children With Cerebral Palsy
Palisano, R. J., Hanna, S. E., Rosenbaum, P. L., Russell, D. J., Walter, S. D., Wood, E. P., Raina, P. S., & Galuppi, B. E. (2000) · Physical Therapy · doi:10.1093/ptj/80.10.974 · Cited by 932
Antepartum risk factors for newborn encephalopathy: the Western Australian case-control study
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Abnormal Cerebral Structure Is Present at Term in Premature Infants
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Origin and timing of brain lesions in term infants with neonatal encephalopathy
Cowan, F., Rutherford, M., Groenendaal, F., Eken, P., Mercuri, E., Bydder, G. M., Meiners, L. C., Dubowitz, L. M., & de Vries, L. S. (2003) · The Lancet · doi:10.1016/s0140-6736(03)12658-x · Cited by 606
Self-citationDevelopment of the Gross Motor Function Classification System for cerebral palsy
Rosenbaum, P. L., Palisano, R. J., Bartlett, D. J., Galuppi, B. E., & Russell, D. J. (2008) · Developmental Medicine & Child Neurology · doi:10.1111/j.1469-8749.2008.02045.x · Cited by 604
Cited by
Cooling for newborns with hypoxic ischaemic encephalopathy
Jacobs, S. E., Berg, M., Hunt, R., Tarnow-Mordi, W. O., Inder, T. E., & Davis, P. G. (2013) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003311.pub3 · Cited by 2,328
Hypoxic-Ischemic Encephalopathy: A Review for the Clinician
Douglas-Escobar, M., & Weiss, M. D. (2015) · JAMA Pediatrics · doi:10.1001/jamapediatrics.2014.3269 · Cited by 778
Outcomes for Extremely Premature Infants
Glass, H. C., Costarino, A. T., Stayer, S. A., Brett, C. M., Cladis, F., & Davis, P. J. (2015) · Anesthesia & Analgesia · doi:10.1213/ane.0000000000000705 · Cited by 733
Effect of Hypothermia on Amplitude-Integrated Electroencephalogram in Infants With Asphyxia
Thoresen, M., Hellström-Westas, L., Liu, X., & de Vries, L. S. (2010) · Pediatrics · doi:10.1542/peds.2009-2938 · Cited by 438
Self-citationThayyil, S., Pant, S., Montaldo, P., Shukla, D., Oliveira, V., Ivain, P., Bassett, P., Swamy, R., Mendoza, J., Moreno-Morales, M., et al. (2021) · The Lancet Global Health · doi:10.1016/s2214-109x(21)00264-3 · Cited by 293
Metadata
- Authors
- Rutherford, M., Ramenghi, L. A., Edwards, A. D., Brocklehurst, P., Halliday, H., Levene, M., Strohm, B., Thoresen, M., Whitelaw, A., & Azzopardi, D.
- Venue
- The Lancet Neurology
- Publisher
- Elsevier BV
- Published
- 2010-01
- Volume
- 9
- Issue
- 1
- Pages
- 39-45
- ISSN
- 1474-4422 (ISSN-L)
- OpenAlex
- W1988501897
- Cited by
- 600
- References
- 33
- FWCI
- 29.22
- Type
- journal article
- Language
- en
- Open access
- hybrid
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