Prognostic Value of Various Diagnostic Methods for Long-Term Outcome of Newborns After Hypoxic-Ischemic Encephalopathy Treated With Hypothermia

Gergeli, Anja Troha; Škofljanec, Andreja; Neubauer, David; Panjan, Darja Paro; Kodrič, Jana; Osredkar, Damjan

doi:10.3389/fped.2022.856615

Cited by 8 publications

(3 citation statements)

References 46 publications

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“…This network outcome association is supported by prior work 13,50 in other ABI populations. Comparatively, a-MRI was the only non-RSN test also associated with the neurological exam, similarly demonstrating its value in the post-cooling era 51 .…”

Section: Coma and Mortalitymentioning

confidence: 86%

Resting State Functional MRI Connectivity Association with Consciousness, Mortality, Longitudinal and Two-Year Outcomes in Neonatal Acute Brain Injury

Boerwinkle

Sussman

Manjón

et al. 2022

Preprint

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Background: An accurate and comprehensive test of integrated brain network function is needed for neonates during the acute brain injury period to inform on morbidity. In our first term neonatal acute brain injury (ABI) study we demonstrated resting state functional MRI (RS) acquired within 31 days of life, results in disrupted connectivity of the resting state fMRI networks, incrementally associated with consciousness, mortality, cognitive and motor development, and ongoing concern for seizures at 6 months post-gestation. In this retrospective cohort study, we evaluate extended 2-year outcomes in the same patients. Methods: Study subjects included the same 40 consecutive neonates from our prior study, with resting state functional MRI acquired within 31 days after suspected brain insult from March 2018 to July 2019. Acute-period exam and test results were assigned ordinal scores based on severity as documented by respective treating specialists. Analyses (Fisher exact, Wilcox Sum-Rank test ordinal/multinomial logistic regression) examined association of resting state networks with demographics, presentation, neurological exam, electroencephalogram, anatomical MRI, magnetic resonance spectroscopy, passive task functional MRI, and outcomes of inpatient and outpatient mortality, outpatient development measured by exam and the Pediatric Cerebral Performance Category Scale (PCPC), motor development and tone, and ongoing concern for seizure at up to 42 months of age. All statistical tests were 2-sided, with statistical significance and CI adjusted using a Bonferroni correction to account for multiple test comparisons for each network and other modality. Results: Subjects had a mean (standard deviation) gestational age of 37.8 (2.6) weeks, follow-up median age follow-up median age (interquartile range) 30.5 (23.6, 36.7) months, 68% were male, with a diagnosis of hypoxic ischemic encephalopathy (60%). Of the 40 patients, three died prior to discharge, and another four between 6-42 months, and 5 were lost to follow-up. Of the followed, findings at birth included mild distress (46%), moderately abnormal neurological exam (34%), and consciousness characterized as awake but irritable (37%). Significant associations after multiple testing corrections were detected for resting state networks: basal ganglia with PCPC (odds ratio [OR], 9.54; 99.4% confidence interval [CI], 1.89-48.1; P = 0.0003), inpatient mortality (OR, 57.5; 99% CI, 1.35->999; P = 0.006), outpatient mortality (OR, 65.7; 99% CI 1.47->999; P = 0.005), and motor tone/weakness (OR, 17.8; 99% CI, 2.2-143; P = 0.0004); language/frontoparietal network with developmental delay (OR, 3.64; 99% CI, 1.02-13.05; P = 0.009), PCPC (OR, 3.98; 99% CI, 1.09-14.45; P = 0.006), and outpatient mortality (OR, 9.2; 99% CI, 0.91-92.6; P = 0.01); default mode network with developmental delay (OR, 4.14; 99% CI, 1.19-14.43; P = 0.003); PCPC (OR, 4.1; 99% CI, 1.2-14.2; P = 0.004), inpatient mortality (OR, 20.41; 99% CI, 0.89-468; P = 0.01), and motor tone/weakness (OR, 3.35; 99% CI, 1.01-11.12; P = 0.009); and seizure onset zone with concern for seizures (OR, 4.02; 99% CI, 1.0-16.15; P = 0.01). Of the other acute phase tests, only anatomical MRI was showed association with and outcome, concern for seizure (OR, 2.40; 99% CI, 0.94-6.13; P = 0.01). Conclusions: This study provides level 3 evidence (OCEBM Levels of Evidence Working Group) demonstrating that in neonatal acute brain injury, the degree of abnormality of resting state networks is associated with mortality, ongoing concern for seizure and 2 year outcomes. These findings suggest RS is feasible and safe to implement in a busy tertiary neonatal ICU and the findings are of at least equivalent value to other standard of care diagnostics.

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Section: Coma and Mortalitymentioning

confidence: 86%

Resting State Functional MRI Connectivity Association with Consciousness, Mortality, Longitudinal and Two-Year Outcomes in Neonatal Acute Brain Injury

Boerwinkle

Sussman

Manjón

et al. 2022

Preprint

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“…To further optimise the reliability of the SE, interest has been directed towards comparing numerical and categorical assessments 20. When assessed within 6 hours of birth, the numerical score of the SE more accurately predicted an abnormal 2-year outcome than the categorical result in infants with mild–moderate HIE; however, in neonates with moderate or severe HIE no difference between numerical and categorical score on SE with respect to associations with MRI injury or long-term outcome were found 20 21 24 26 27. By using a different approach, assessing the change in numerical score from qSE to rSE, we identified an association with death/NDI: for each unit increase in score, the odds for death or NDI increased whereas for each unit decrease, the odds lowered.…”

Section: Discussionmentioning

confidence: 99%

Evolution of the Sarnat exam and association with 2-year outcomes in infants with moderate or severe hypoxic-ischaemic encephalopathy: a secondary analysis of the HEAL Trial

Mietzsch,

Kolnik,

Wood

et al. 2023

Arch Dis Child Fetal Neonatal Ed

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ObjectiveTo study the association between the Sarnat exam (SE) performed before and after therapeutic hypothermia (TH) and outcomes at 2 years in infants with moderate or severe hypoxic-ischaemic encephalopathy (HIE).DesignSecondary analysis of theHigh-doseErythropoietin forAsphyxia and EncephaLopathy Trial. Adjusted ORs (aORs) for death or neurodevelopmental impairment (NDI) based on SE severity category and change in category were constructed, adjusting for sedation at time of exam. Absolute SE Score and its change were compared for association with risk for death or NDI using locally estimated scatterplot smoothing curves.SettingRandomised, double-blinded, placebo-controlled multicentre trial including 17 centres across the USA.Patients479/500 enrolled neonates who had both a qualifying SE (qSE) before TH and a SE after rewarming (rSE).InterventionsStandardised SE was used across sites before and after TH. All providers underwent standardised SE training.Main outcome measuresPrimary outcome was defined as the composite outcome of death or any NDI at 22–36 months.ResultsBoth qSE and rSE were associated with the primary outcome. Notably, an aOR for primary outcome of 6.2 (95% CI 3.1 to 12.6) and 50.3 (95% CI 13.3 to 190) was seen in those with moderate and severe encephalopathy on rSE, respectively. Persistent or worsened severity on rSE was associated with higher odds for primary outcome compared with those who improved, even when qSE was severe.ConclusionBoth rSE and change between qSE and rSE were strongly associated with the odds of death/NDI at 22–36 months in infants with moderate or severe HIE.

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“…Identifying early and non-invasive biomarkers to predict children’s prognoses and neurodevelopmental outcomes is particularly complicated in children with moderate disease, and it is crucial to provide fact-based awareness to worried parents and to plan an early, multidisciplinary, and tailored treatment for patients [ 12 , 13 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Predictive Value of MRI in Hypoxic-Ischemic Encephalopathy Treated with Therapeutic Hypothermia

et al. 2023

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Background: Hypoxic-ischemic encephalopathy (HIE) is a severe pathology, and no unique predictive biomarker has been identified. Our aims are to identify associations of perinatal and outcome parameters with morphological anomalies and ADC values from MRI. The secondary aims are to define a predictive ADC threshold value and detect ADC value fluctuations between MRIs acquired within 7 days (MR0) and at 1 year (MR1) of birth in relation to perinatal and outcome parameters. Methods: Fifty-one term children affected by moderate HIE treated with hypothermia and undergoing MRI0 and MRI1 were recruited. Brain MRIs were evaluated through the van Rooij score, while ADC maps were co-registered on a standardized cerebral surface, on which 29 ROIs were drawn. Statistical analysis was performed in Matlab, with the statistical significance value at 0.05. Results: ADC0 < ADC1 in the left and right thalami, left and right frontal white matter, right visual cortex, and the left dentate nucleus of children showing abnormal perinatal and neurodevelopmental parameters. At ROC analysis, the best prognostic ADC cut-off value was 1.535 mm2/s × 10−6 (sensitivity 80%, specificity 86%) in the right frontal white matter. ADC1 > ADC0 in the right visual cortex and left dentate nucleus, positively correlated with multiple abnormal perinatal and neurodevelopmental parameters. The van Rooij score was significantly higher in children presenting with sleep disorders. Conclusions: ADC values could be used as prognostic biomarkers to predict children’s neurodevelopmental outcomes. Further studies are needed to address these crucial topics and validate our results. Early and multidisciplinary perinatal evaluation and the subsequent re-assessment of children are pivotal to identify physical and neuropsychological disorders to guarantee early and tailored therapy.

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Prognostic Value of Various Diagnostic Methods for Long-Term Outcome of Newborns After Hypoxic-Ischemic Encephalopathy Treated With Hypothermia

Cited by 8 publications

References 46 publications

Resting State Functional MRI Connectivity Association with Consciousness, Mortality, Longitudinal and Two-Year Outcomes in Neonatal Acute Brain Injury

Resting State Functional MRI Connectivity Association with Consciousness, Mortality, Longitudinal and Two-Year Outcomes in Neonatal Acute Brain Injury

Evolution of the Sarnat exam and association with 2-year outcomes in infants with moderate or severe hypoxic-ischaemic encephalopathy: a secondary analysis of the HEAL Trial

Predictive Value of MRI in Hypoxic-Ischemic Encephalopathy Treated with Therapeutic Hypothermia

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