MRI combined with early clinical variables are excellent outcome predictors for newborn infants undergoing therapeutic hypothermia after perinatal asphyxia
Marianne Thoresen, Sally Jary, Lars Walløe, Mathias Karlsson, Miriam Martínez-Biarge, Ela Chakkarapani, Frances M. Cowan
Abstract
BACKGROUND: Binary prediction-models for outcome [death, cognition, presence and severity of cerebral palsy (CP)], using MRI and early clinical data applicable for individual outcome prediction have not been developed. METHODS: = 12) using CoolCap/TOBY-trial entry-criteria including depressed amplitude-integrated EEG (aEEG). Early clinical/biochemical variables and MRI scans (median day 8) were obtained in 168 infants. Injury severity was scored for cortex, basal ganglia/thalami (BGT), white matter (WM) and posterior limb of the internal capsule, summating to a total injury score (TIS, range 0-11). Outcome was categorized as adverse or favourable at 18-24 months from Bayley-III domains (cut-off 85) and neurological examination including CP classification. FINDINGS: HIE and entry-aEEG severity were stable throughout the study. Outcome was favourable in 133/178 infants and adverse in 45/178: 17 died, 28 had low Cognition/Language scores, (including 9 with severe CP and 6 mild); seven had mild CP with favourable cognitive outcome. WMxBGT product scores and TIS were strong outcome predictors, and prediction improved when clinical/biochemical variables were added in binary logistic regression. The Positive Predictive Value for adverse outcome was 88%, increasing to 95% after excluding infants with PNC and additional diagnoses. Using WMxBGT in the regression predicted 8 of the 9 children with severe CP. INTERPRETATION: Binary logistic regression with WMxBGT or TIS and clinical variables gave excellent outcome prediction being 12% better than single variable cross-tabulation. Our MRI scoring and regression models are readily accessible and deserve investigation in other cohorts for group and individual prediction. FUNDING: We thank the National Health Service (NHS) and our Universities and funders in UK and Norway: SPARKS, The Moulton Foundation, The Norwegian Research Council, The Lærdal Foundation for Acute Medicine and charitable donations for their support for cooling therapy.