Two-Year Neurodevelopmental Outcomes After Mild Hypoxic Ischemic Encephalopathy in the Era of Therapeutic Hypothermia

Finder, Mikael; Boylan, Geraldine B.; Twomey, Deirdre; Ahearne, Caroline; Murray, Deirdre M.; Hallberg, Boubou

doi:10.1001/jamapediatrics.2019.4011

Cited by 157 publications

(124 citation statements)

References 35 publications

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“…In neonates with mild HIE, not treated with TH, although the developmental scores were within normal range, cognitive outcomes were significantly lower compared with healthy controls (OR ¼ À7.0; 95% CI ¼ À11.0 to À3.0), and more similar to infants with moderate HIE treated with TH. 42 In the eight infants with mild HIE who were treated with hypothermia, their developmental outcomes were noted to be similar to moderate HIE treated with TH. Interestingly, none of the mild HIE infants, not treated with hypothermia, progressed to more severe encephalopathy.…”

Section: Discussionmentioning

confidence: 87%

“…31 Two recent nonrandomized cohort studies also offer further contrasting insights into this issue. 42,43 Finder et al compared outcomes of neonates with mild HIE across a multicenter prospectively enrolled cohort of neonates with perinatal asphyxia. 42 They noted the severity as the worst stage of encephalopathy in the first 24 hours of age, and stratified them into different categories that included normal or mild HIE at the time of discharge.…”

Section: Discussionmentioning

confidence: 99%

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Utilization of Therapeutic Hypothermia and Neurological Injury in Neonates with Mild Hypoxic-Ischemic Encephalopathy: A Report from Children's Hospital Neonatal Consortium

et al. 2020

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Objective This study was aimed to describe utilization of therapeutic hypothermia (TH) in neonates presenting with mild hypoxic-ischemic encephalopathy (HIE) and associated neurological injury on magnetic resonance imaging (MRI) scans in these infants. Study Design Neonates ≥ 36 weeks' gestation with mild HIE and available MRI scans were identified. Mild HIE status was assigned to hyper alert infants with an exaggerated response to arousal and mild HIE as the highest grade of encephalopathy recorded. MRI scans were dichotomized as “injury” versus “no injury.” Results A total of 94.5% (257/272) neonates with mild HIE, referred for evaluation, received TH. MRI injury occurred in 38.2% (104/272) neonates and affected predominantly the white matter (49.0%, n = 51). Injury to the deep nuclear gray matter was identified in (10.1%) 20 infants, and to the cortex in 13.4% (n = 14 infants). In regression analyses (odds ratio [OR]; 95% confidence interval [CI]), history of fetal distress (OR = 0.52; 95% CI: 0.28–0.99) and delivery by caesarian section (OR = 0.54; 95% CI: 0.31–0.92) were associated with lower odds, whereas medical comorbidities during and after cooling were associated with higher odds of brain injury (OR = 2.31; 95% CI: 1.37–3.89). Conclusion Majority of neonates with mild HIE referred for evaluation are being treated with TH. Odds of neurological injury are over two-fold higher in those with comorbidities during and after cooling. Brain injury predominantly involved the white matter. Key Points

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Utilization of Therapeutic Hypothermia and Neurological Injury in Neonates with Mild Hypoxic-Ischemic Encephalopathy: A Report from Children's Hospital Neonatal Consortium

et al. 2020

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“…Neonatal hypoxic-ischemic encephalopathy (HIE) occurs in as many as 6 infants per 1,000 live births (1)(2)(3)(4). While there is likely an acute event occurring around delivery, the injury observed in HIE is likely a combination of acute on chronic injury (5).…”

Section: Introductionmentioning

confidence: 99%

“…Children with a history of HIE are at high risk of abnormal cognitive development. Unfortunately, more than half of infants have abnormal neurodevelopment following HIE (1,7). Additionally, even those infants with mild HIE, previously thought to have normal outcomes, have been observed to have abnormal neurodevelopment with deficits apparent in childhood including lower cognitive composite scores (1,8).…”

Section: Introductionmentioning

confidence: 99%

“…Unfortunately, more than half of infants have abnormal neurodevelopment following HIE (1,7). Additionally, even those infants with mild HIE, previously thought to have normal outcomes, have been observed to have abnormal neurodevelopment with deficits apparent in childhood including lower cognitive composite scores (1,8). While executive function is an umbrella term used to describe the processes necessary to achieve goal-directed behavior, multiple domain specific deficits have been reported after HIE in children.…”

Section: Introductionmentioning

confidence: 99%

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Neonatal Hypoxic-Ischemic Encephalopathy Yields Permanent Deficits in Learning Acquisition: A Preclinical Touchscreen Assessment

et al. 2020

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Neonatal hypoxic-ischemic encephalopathy (HIE) remains a common problem worldwide for infants born at term. The impact of HIE on long-term outcomes, especially into adulthood, is not well-described. To facilitate identification of biobehavioral biomarkers utilizing a translational platform, we sought to investigate the impact of HIE on executive function and cognitive outcomes into adulthood utilizing a murine model of HIE. HIE mice (unilateral common carotid artery occlusion to induce ischemia, followed by hypoxia with a FiO 2 of 0.08 for 45 min) and control mice were tested on discrimination and reversal touchscreen tasks (using their noses) shown to be sensitive to loss of basal ganglia or cortical function, respectively. We hypothesized that the HIE injury would result in deficits in reversal learning, revealing complex cognitive and executive functioning impairments. Following HIE, mice had a mild discrimination impairment as measured by incorrect responses but were able to learn the paradigm to similar levels as controls. During reversal, HIE mice required significantly more total trials, errors and correction trials across the paradigm. Analysis of specific stages showed that reversal impairments in HIE were driven by significant increases in all measured parameters during the late learning, striatal-mediated portion of the task. Together, these results support the concept that HIE occurring during the neonatal period results in abnormal neurodevelopment that persists into adulthood, which can impact efficient associated learning. Further, these data show that utilization of an established model of HIE coupled with touchscreen learning provides valuable information for screening therapeutic interventions that could mitigate these deficits to improve the long-term outcomes of this vulnerable population.

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Association of Acute Respiratory Failure in Early Childhood With Long-term Neurocognitive Outcomes

Watson

Beers

Asaro

et al. 2022

JAMA

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Key PointsQuestionDo children with previously normal neurocognitive function who survive an episode of acute respiratory failure requiring intensive care and invasive mechanical ventilation have worse long-term neurocognitive function than their matched siblings?FindingsIn this cohort study that included 121 sibling pairs, children discharged from intensive care hospitalization for respiratory failure without severe cognitive dysfunction compared with their matched siblings had a mean IQ score of 101.5 vs 104.3, a difference that was statistically significant.MeaningAcute respiratory failure in early childhood was associated with a slightly, but statistically significant, lower subsequent IQ score.

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Two-Year Neurodevelopmental Outcomes After Mild Hypoxic Ischemic Encephalopathy in the Era of Therapeutic Hypothermia

Cited by 157 publications

References 35 publications

Utilization of Therapeutic Hypothermia and Neurological Injury in Neonates with Mild Hypoxic-Ischemic Encephalopathy: A Report from Children's Hospital Neonatal Consortium

Utilization of Therapeutic Hypothermia and Neurological Injury in Neonates with Mild Hypoxic-Ischemic Encephalopathy: A Report from Children's Hospital Neonatal Consortium

Neonatal Hypoxic-Ischemic Encephalopathy Yields Permanent Deficits in Learning Acquisition: A Preclinical Touchscreen Assessment

Association of Acute Respiratory Failure in Early Childhood With Long-term Neurocognitive Outcomes

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