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 has not been developed.
Methods From Dec1st 2006 until Dec31st 2013, we recruited 178 infants into a population-based cohort with moderate or severe hypoxic ischemic encephalopathy(HIE) including postnatal collapse (PNC, n=12) and additional diagnoses (n=12) using CoolCap/TOBY-trial entry-criteria including depressed amplitude-integrated EEG(aEEG). Early clinical/biochemical variables and MRI scans were obtained in 168 infants (median day 8). 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 favorable 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 favorable 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 favorable 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 PNC and additional diagnoses. Using WMxBGT in the regression predicted 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.
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 has not been developed.
Methods From Dec1st 2006 until Dec31st 2013, we recruited 178 infants into a population-based cohort with moderate or severe hypoxic ischemic encephalopathy(HIE) including postnatal collapse (PNC, n=12) and additional diagnoses (n=12) using CoolCap/TOBY-trial entry-criteria including depressed amplitude-integrated EEG(aEEG). Early clinical/biochemical variables and MRI scans were obtained in 168 infants (median day 8). 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 favorable 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 favorable 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 favorable 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 PNC and additional diagnoses. Using WMxBGT in the regression predicted 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.
| Original language | English |
|---|---|
| Article number | 100885 |
| Number of pages | 12 |
| Journal | EClinicalMedicine |
| Volume | 36 |
| Early online date | 17 May 2021 |
| DOIs | |
| Publication status | Published - Jun 2021 |
Bibliographical note
Funding Information:The staff maintaining the database were supported by the UK children's charity SPARKS and external charitable donations. Equipment used to cool the patients and the aEEG machines to monitor the brain were supported by the Moulton foundation , the Lærdal Foundation for Acute Medicine and charitable donations. Use of the MRI scanners were supported by grants, the National Health Service and the University of Bristol . Clinical and research staff were supported by the National Health Service, the University of Bristol and the University of Oslo through their salaries.
Funding Information:
The staff maintaining the database were supported by the UK children's charity SPARKS and external charitable donations. Equipment used to cool the patients and the aEEG machines to monitor the brain were supported by the Moulton foundation, the L?rdal Foundation for Acute Medicine and charitable donations. Use of the MRI scanners were supported by grants, the National Health Service and the University of Bristol. Clinical and research staff were supported by the National Health Service, the University of Bristol and the University of Oslo through their salaries.
Publisher Copyright:
© 2021 The Authors
Keywords
- therapeutic hypothermia
- moderate or severe perinatal asphyxia
- hypoxic-ischaemic encephalopathy
- neonatal seizures
- neurodevelopmental outcome
- Bayley-III
- cerebral palsy
- MRI
- T1 and T2
- white matter
- basal ganglia and thalamus
- posterior limb of the internal capsule
- cortex
- outcome prediction
- logistic regression