Systemic Hypothermia After Neonatal Encephalopathy: Outcomes of neo.nEURO.network RCT

Simbruner, G.; Mittal, Rakhi; Rohlmann, Friederike; Muche, Rainer

doi:10.1542/peds.2009-2441

Cited by 420 publications

(317 citation statements)

References 24 publications

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“…7 Other trials of whole-body or head-only cooling with whole-body hypothermia for neonatal encephalopathy have shown beneficial outcomes of hypothermia at 18 to 24 months of age in the entire study cohorts and in selected subgroups. [7][8][9] In the present study assessing children at 6 to 7 years of age, the difference in rates of the composite outcome of death or an IQ score below 70 between hypothermia and usual care did not achieve statistical significance (P = 0.06); however, the previous finding of reduced mortality with hypothermia was maintained, with no appreciable increase in the risk of neurodevelopmental deficits among survivors.…”

Section: Discussioncontrasting

confidence: 71%

Effect of hypothermia for perinatal asphyxia on childhood outcomes

Jose¹,

Ismael²

2017

Int J Contemp Pediatr

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Background: Perinatal asphyxia, neonatal asphyxia or birth asphyxia is the medical condition resulting from deprivation of oxygen to a new born infant that lasts long enough during the birth process to cause physical harm, usually to the brain. This study was performed to evaluate study population who were 6 to 8 years of age to determine whether the application of moderate hypothermia after perinatal asphyxia is associated with long term benefits.Methods: This study was a randomised, controlled trials which consisted of infants who were admitted with moderate and severe encephalopathy within 6 hours after birth after an acute perinatal event, with acidosis or resuscitation. Infants were assigned to undergo whole body hypothermia at 33ºC for 72 hours or to undergo usual care randomly.Results: All maternal baseline characteristics and Neonatal characteristics are non significant in both groups. APGAR score ≤5 is significant at 10mins in comparison. cerebral palsy were 18% and 25%, respectively, the rates of blindness were 1% and 4% the rates of hearing impairment (requiring aids) were 5.4% and 12.8%. There were no significant between-group differences in the level of disability among all survivors or in motor function among the 45 nondisabled children. Among children who had moderate or severe disability at 18 months, the corresponding rates at 6 to 7 years of age were 88% in the hypothermia group and 95% in the control group. All the children who had moderate-to-severe cerebral palsy at 18 months continued to be affected at 6 to 7 years in both groups. There was no significant between-group difference with respect to IQ scores that were measured on a continuous scale and other scores, with the exception of 1 of the 11 scores compared (attention and executive function, P=0.03). There were also no significant differences between groups in mean scores on the index of health care status derived from parental assessments or in parental scores for children’s strengths and difficulties and ADHD The mean difference in the academic achievement score favored the hypothermia group but was not significant.Conclusions: Moderate hypothermia after perinatal asphyxia resulted in improved neurocognitive outcomes in middle childhood.

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Section: Discussioncontrasting

confidence: 71%

Effect of hypothermia for perinatal asphyxia on childhood outcomes

Jose¹,

Ismael²

2017

Int J Contemp Pediatr

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“…In contrast, cooling studies from therapeutic referral centres, whose subject samples may differ from centre to centre, give estimates of the proportions of subjects with potentially asphyxial birth events, ranging from 40% to 60%. [7][8][9] Since these trials were published, reports of cooling for the treatment of HIE, outside a clinical trial setting, indicate that between 22% 10 and 51% 11 of those treated experienced a potentially asphyxial birth event, suggesting substantial differences between different referral centre groups. These findings also suggest that, in the case of some infants being treated with therapeutic hypothermia, the timing and nature of injury are not obviously hypoxic-ischaemic.…”

Section: Sources Of Difference Between Conclusion Drawn From Populatmentioning

confidence: 99%

Does aetiology of neonatal encephalopathy and hypoxic–ischaemic encephalopathy influence the outcome of treatment?

McIntyre

Badawi

Blair

et al. 2015

Develop Med Child Neuro

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HIE Hypoxic-ischaemic encephalopathyNeonatal encephalopathy, a clinical syndrome affecting term-born and late preterm newborn infants, increases the risk of perinatal death and long-term neurological morbidity, especially cerebral palsy. With the advent of therapeutic hypothermia, a treatment designed for hypoxic or ischaemic injury, associated mortality and morbidity rates have decreased. Unfortunately, only about one in eight neonates (95% confidence interval) who meet eligibility criteria for therapeutic cooling apparently benefit from the treatment. Studies of infants in representative populations indicate that neonatal encephalopathy is a potential result of a variety of antecedents and that asphyxial complications at birth account for only a small percentage of neonatal encephalopathy. In contrast, clinical case series suggest that a large proportion of neonatal encephalopathy is hypoxic or ischaemic, and trials of therapeutic hypothermia are specifically designed to include only infants exposed to hypoxia or ischaemia. This review addresses the differences, definitional and methodological, between infants studied and investigations undertaken, in population studies compared with cooling trials. It raises the question if there may be subgroups of infants with a clinical diagnosis of hypoxic-ischaemic encephalopathy (HIE) in whom the pathobiology of neonatal neurological depression is not fundamentally hypoxic or ischaemic and, therefore, for whom cooling may not be beneficial. In addition, it suggests approaches to future trials of cooling plus adjuvant therapy that may contribute to further improvement of care for these vulnerable neonates.Neonatal encephalopathy is a clinical syndrome of disordered neurological function occurring in the first days of life in term-born and late preterm neonates and is characterized by difficulty initiating and maintaining respiration, an abnormal level of consciousness, depression of tone and reflex responses, and often seizures. This symptom complex affects about 3 in every 1000 births, and is an important predictor of perinatal death and a major contributor to long-term adverse neurological outcomes, particularly cerebral palsy (CP). 1,2 Evidence from clinical and experimental studies agrees that some instances of neonatal encephalopathy are related to hypoxic-ischaemic injury, but the proportions of neonatal encephalopathy attributed to recent asphyxial events vary with the definitions used and the methodology of the investigations. Studies of infants in representative populations indicate that asphyxial complications at birth account for only a minority of neonatal encephalopathy. These population-based studies also identify other factors that contribute to increased risk of neonatal encephalopathy, such as intrauterine exposure to inflammation or fetal growth restriction, and note that some non-asphyxial factors can produce a clinical picture that closely mimics hypoxia-ischaemia. [3][4][5] In contrast, studies of neonatal cooling have approached this topic from the ...

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“…3 Up to 12 000 infants are affected each year in the United States. Although therapeutic hypothermia provides modest improvements in outcome, [4][5][6][7][8] >40% of infants who received this therapy in clinical trials either died or suffered moderate to severe disabilities, including cerebral palsy, intellectual impairment, and epilepsy. [5][6][7][8][9] Adjuvant neuroprotective therapies are needed to further improve outcomes after HIE.…”

mentioning

confidence: 99%

High-Dose Erythropoietin and Hypothermia for Hypoxic-Ischemic Encephalopathy: A Phase II Trial

Mathur²,

et al. 2016

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OBJECTIVE: To determine if multiple doses of erythropoietin (Epo) administered with hypothermia improve neuroradiographic and short-term outcomes of newborns with hypoxic-ischemic encephalopathy. METHODS:In a phase II double-blinded, placebo-controlled trial, we randomized newborns to receive Epo (1000 U/kg intravenously; n = 24) or placebo (n = 26) at 1, 2, 3, 5, and 7 days of age. All infants had moderate/severe encephalopathy; perinatal depression (10 minute Apgar <5, pH <7.00 or base deficit ≥15, or resuscitation at 10 minutes); and received hypothermia. Primary outcome was neurodevelopment at 12 months assessed by the Alberta Infant Motor Scale and Warner Initial Developmental Evaluation. Two independent observers rated MRI brain injury severity by using an established scoring system. RESULTS:The mean age at first study drug was 16.5 hours (SD, 5.9). Neonatal deaths did not significantly differ between Epo and placebo groups (8% vs 19%, P = .42). Brain MRI at mean 5.1 days (SD, 2.3) showed a lower global brain injury score in Epo-treated infants (median, 2 vs 11, P = .01). Moderate/severe brain injury (4% vs 44%, P = .002), subcortical (30% vs 68%, P = .02), and cerebellar injury (0% vs 20%, P = .05) were less frequent in the Epo than placebo group. At mean age 12.7 months (SD, 0.9), motor performance in Epotreated (n = 21) versus placebo-treated (n = 20) infants were as follows: Alberta Infant Motor Scale (53.2 vs 42.8, P = .03); Warner Initial Developmental Evaluation (28.6 vs 23.8, P = .05).CONCLUSIONS: High doses of Epo given with hypothermia for hypoxic-ischemic encephalopathy may result in less MRI brain injury and improved 1-year motor function.

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Systemic Hypothermia After Neonatal Encephalopathy: Outcomes of neo.nEURO.network RCT

Abstract: Systemic hypothermia in the neo.nEURO.network trial showed a strong neuroprotective effect and was effective in the severe HIE group.

Cited by 420 publications

References 24 publications

Effect of hypothermia for perinatal asphyxia on childhood outcomes

Effect of hypothermia for perinatal asphyxia on childhood outcomes

Does aetiology of neonatal encephalopathy and hypoxic–ischaemic encephalopathy influence the outcome of treatment?

High-Dose Erythropoietin and Hypothermia for Hypoxic-Ischemic Encephalopathy: A Phase II Trial

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