Residual brain injury after early discontinuation of cooling therapy in mild neonatal encephalopathy

Lally, Peter J; Montaldo, Paolo; Oliveira, Vânia; Swamy, Ravi; Soe, Aung; Shankaran, Seetha; Thayyil, Sudhin

doi:10.1136/archdischild-2017-313321

Cited by 27 publications

(15 citation statements)

References 10 publications

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“…In fact, a recent report highlighted that some centers are treating neonates with mild encephalopathy but discontinuing cooling before completion of 72 hours of hypothermia; more than 50% of these neonates had injury on MRI and 20% had developmental delays including language delay. 32 Others have suggested that the presence of clinical encephalopathy (including mild) and changes in neurophysiology (EEG) and not acidosis alone are associated with injury on MRI and with adverse outcomes in the neonatal period and beyond. 9,30,33 Skranes et al noted neonates with abnormal initial (at onset of cooling) amplitude-integrated EEG (aEEG) background were at risk of more MR injury and worse cognitive outcomes.…”

Section: Discussionmentioning

confidence: 99%

Neurodevelopmental Outcomes in Neonates with Mild Hypoxic Ischemic Encephalopathy Treated with Therapeutic Hypothermia

Rao

Trivedi²,

Distler

et al. 2019

Amer J Perinatol

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Objective To review developmental outcomes of neonates with mild hypoxic-ischemic encephalopathy (HIE) treated with therapeutic hypothermia (TH). Study Design Neonates ≥35 weeks' gestation with mild HIE/TH (TH group, n = 30) were matched with healthy term-born infants (control group, n = 30) and reviewed for the presence and severity of magnetic resonance imaging (MRI)-detected neurological injury. Neurodevelopmental outcomes were assessed using the Bayley Scales of Infant Development (BSID). Results MRI injury was present in 13/30 (43.3%) neonates (11 mild, 1 moderate, and 1 severe injuries) in the TH group. The mean (standard deviation [SD]) corrected age at BSID III was 29.3 (3.9) months in the controls compared with 14.7 (3.9) months in the TH group (p < 0.01). The mean (SD) cognitive, language, and motor composite scores in neonates in the TH group (n = 16, 53.3%) and control groups (n = 30, 100%) were 99.4 (17.1) versus 93.0 (12.3), (p = 0.15), 89.5 (15.5) versus 100.2 (18.4), (p = 0.054), and 93.1 (15.4) versus 100.8 (16.3) (p = 0.13), respectively. Conclusion Developmental outcomes of neonates with mild HIE/TH were similar to healthy, term-born neonates.

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Section: Discussionmentioning

confidence: 99%

Neurodevelopmental Outcomes in Neonates with Mild Hypoxic Ischemic Encephalopathy Treated with Therapeutic Hypothermia

Rao

Trivedi²,

Distler

et al. 2019

Amer J Perinatol

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“…Although the numbers were small, our study suggests that cooling for less than 24 hours is unlikely to be beneficial in mild HIE, as there was no difference in the metabolite profile of non-cooled and partially cooled babies. We previously demonstrated that there was MRI evidence of residual brain injury in 50% of the babies with mild HIE who were cooled for less than 24 hours, and 20% of them subsequently had adverse outcomes 20. Whether cooling for 24 or 48 hours is as good or better than cooling for 72 hours in mild HIE is not known.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic hypothermia initiated within 6 hours of birth is associated with reduced brain injury on MR biomarkers in mild hypoxic-ischaemic encephalopathy: a non-randomised cohort study

Montaldo

Lally

Oliveira

et al. 2018

Arch Dis Child Fetal Neonatal Ed

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ObjectiveTo examine the effect of therapeutic hypothermia on MR biomarkers and neurodevelopmental outcomes in babies with mild hypoxic-ischaemic encephalopathy (HIE).DesignNon-randomised cohort study.SettingEight tertiary neonatal units in the UK and the USA.Patients47 babies with mild HIE on NICHD neurological examination performed within 6 hours after birth.InterventionsWhole-body cooling for 72 hours (n=32) or usual care (n=15; of these 5 were cooled for <12 hours).Main outcome measuresMRI and MR spectroscopy (MRS) within 2 weeks after birth, and a neurodevelopmental outcome assessment at 2 years.ResultsThe baseline characteristics in both groups were similar except for lower 10 min Apgar scores (p=0.02) in the cooled babies. Despite this, the mean (SD) thalamic NAA/Cr (1.4 (0.1) vs 1.6 (0.2); p<0.001) and NAA/Cho (0.67 (0.08) vs 0.89 (0.11); p<0.001) ratios from MRS were significantly higher in the cooled group. Cooled babies had lower white matter injury scores than non-cooled babies (p=0.02). Four (27%) non-cooled babies with mild HIE developed seizures after 6 hours of age, while none of the cooled babies developed seizures (p=0.008). Neurodevelopmental outcomes at 2 years were available in 40 (85%) of the babies. Adverse outcomes were seen in 2 (14.3%) non-cooled babies, and none of the cooled babies (p=0.09).ConclusionsTherapeutic hypothermia may have a neuroprotective effect in babies with mild HIE, as demonstrated by improved MRS biomarkers and reduced white matter injury on MRI. This may warrant further evaluation in adequately powered randomised controlled trials.

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“…There is no established prognostic method by which clinicians can determine if it is possible to stop cooling before 72 hours [63], and so hypothermia should be continued for 3 days. Supporting this concept, in one case series of 10 infants with mild HIE in whom hypothermia was stopped early because of rapid clinical improvement, neural injury on magnetic resonance imaging was seen in half and disability at 2 years of age in 2 infants [64]. Given that there are roughly as many infants with mild HIE as there are with moderate to severe HIE, it is critical that the benefits of treatment for this group should be formally tested.…”

Section: Other Populations: Should We Cool Infants With Mild Hie?mentioning

confidence: 99%

Therapeutic Hypothermia in Neonatal Hypoxic-Ischemic Encephalopathy

Wassink

Davidson

Dhillon

et al. 2019

Curr Neurol Neurosci Rep

120

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Purpose of review -therapeutic hypothermia reduces death or disability in term and near-term infants with moderate-severe hypoxic-ischemic encephalopathy. Nevertheless, many infants still survive with disability, despite hypothermia, supporting further research into ways to further improve neurologic outcomes. Recent findings -recent clinical and experimental studies have refined our understanding of the key parameters for hypothermic neuroprotection, including timing of initiation, depth, and duration of hypothermia, and subsequent rewarming rate. However, important knowledge gaps remain. There is encouraging clinical evidence from a small phase II trial that combined treatment of hypothermia with recombinant erythropoietin further reduces risk of disability but definitive studies are still needed. Summary -In conclusion, recent studies suggest that current protocols for therapeutic hypothermia are nearoptimal, and that the key to better neurodevelopmental outcomes is earlier diagnosis and initiation of hypothermia after birth. Further research is essential to find and evaluate ways to further improve outcomes after hypoxic-ischemic encephalopathy, including add-on therapies for therapeutic hypothermia and preventing pyrexia during labor and delivery.

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Residual brain injury after early discontinuation of cooling therapy in mild neonatal encephalopathy

Cited by 27 publications

References 10 publications

Neurodevelopmental Outcomes in Neonates with Mild Hypoxic Ischemic Encephalopathy Treated with Therapeutic Hypothermia

Neurodevelopmental Outcomes in Neonates with Mild Hypoxic Ischemic Encephalopathy Treated with Therapeutic Hypothermia

Therapeutic hypothermia initiated within 6 hours of birth is associated with reduced brain injury on MR biomarkers in mild hypoxic-ischaemic encephalopathy: a non-randomised cohort study

Therapeutic Hypothermia in Neonatal Hypoxic-Ischemic Encephalopathy

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