Magnetic resonance spectroscopy assessment of brain injury after moderate hypothermia in neonatal encephalopathy: a prospective multi-centre study

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Title: Magnetic resonance spectroscopy assessment of brain injury after moderate hypothermia in neonatal encephalopathy: a prospective multi-centre study
Authors: Lally, PJ
Montaldo, P
Oliveira, V
Soe, A
Swamy, R
Bassett, P
Mendoza, J
Atreja, G
Kariholu, U
Pattnayak, S
Sashikumar, P
Harizaj, H
Mitchell, M
Ganesh, V
Harigopal, S
Dixon, J
English, P
Clarke, P
Muthukumar, P
Satodia, P
Wayte, S
Abernethy, LJ
Yajamanyam, K
Bainbridge, A
Price, D
Huertas, A
Sharp, DJ
Kalra, V
Chawla, S
Shankaran, S
Thayyil, S
Item Type: Journal Article
Abstract: Background In neonatal encephalopathy (NE), the clinical manifestations of injury can only be reliably assessed several years after an intervention, complicating early prognostication and rendering trials of promising neuroprotectants slow and expensive. We aimed to determine the accuracy of thalamic proton magnetic resonance spectroscopy (1H MRS) biomarkers as early predictors of the neurodevelopmental abnormalities observed years after NE. Methods We conducted a prospective multi-centre cohort study across eight neonatal intensive care units, recruiting term neonates who received therapeutic hypothermia for NE. We obtained thalamic 1H MRS 4 to 14 days after birth, which were compared to clinical neurodevelopmental tests performed 18 to 24 months later. The primary endpoint was an abnormal outcome, defined as death, or moderate or severe disability. Receiver operating characteristic (ROC) curves were used to examine the strength of the relationship between selected biomarkers and this outcome. Findings We recruited 223 infants who all underwent MR imaging and spectroscopy at a median (IQR) age of 7 (5 to 10) days, with 190 (85%) followed up for neurological examination at a median (IQR) age of 23 (20 to 25) months. Of those followed up, 31 (16%) had moderate or severe disability, including one death. The thalamic concentration of Nacetylasparate, [NAA], had an area under the ROC curve (AUC) of 0·99 (95% CI 0·94 to 1·00, n=82), and lactate/NAA peak area ratio had an AUC of 0·94 (95% CI 0·89 to 0·97, n=160). From conventional MRI, abnormal signal in the posterior limb of the internal capsule (PLIC) gave an AUC of 0·82 (95% CI 0·76 to 0·87, n=190). Thalamic [NAA] was independently associated with neurodevelopmental outcome scores on multivariable analysis, and had higher prognostic accuracy than conventional MR imaging (98% versus 87%; p<0·001). Interpretation Thalamic 1H MRS measures acquired soon after birth in NE accurately predict neurodevelopment two years later. These could be applied to increase the power of neuroprotection trials, while reducing their duration.
Issue Date: 14-Nov-2018
Date of Acceptance: 26-Aug-2018
URI: http://hdl.handle.net/10044/1/63908
ISSN: 1474-4422
Publisher: Elsevier
Journal / Book Title: Lancet Neurology
Copyright Statement: This paper is embargoed until publication. Once published it will be available fully open access.
Sponsor/Funder: National Institute for Health Research
Medical Research Council
Funder's Grant Number: NIHR/CS/010/022
MR/R001375/1
Keywords: 1103 Clinical Sciences
1109 Neurosciences
Neurology & Neurosurgery
Publication Status: Accepted
Embargo Date: publication subject to indefinite embargo
Appears in Collections:Department of Medicine
Faculty of Medicine



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