Effect of therapeutic hypothermia on chromosomal aberration in perinatal asphyxia

Gane, Bahubali D; Nandhakumar, S.; Bhat, Vishnu; Rao, Ramachandra

doi:10.4103/1817-1745.181269

Cited by 5 publications

(3 citation statements)

References 12 publications

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“…The largest of these was a clinical trial from China involving 194 neonates [ 55 ], but this trial has been heavily criticized for protocol violations, post-randomisation exclusion and poor follow-up rates. Six of these cooling trials were from the same hospital, but with mortality in the usual care arm varying between 7 % and 50 %, raising concerns about data credibility and duplicate publications [ [56] , [57] , [58] , [59] , [60] , [61] ]. Hence, although the pooled data from these trials show a reduction in mortality with cooling, such a meta-analysis has no scientific value [ 62 , 63 ] ( Fig.…”

Section: Introductionmentioning

confidence: 99%

Need for more evidence in the prevention and management of perinatal asphyxia and neonatal encephalopathy in low and middle-income countries: A call for action

Krishnan

Kumar

Variane³

et al. 2021

Seminars in Fetal and Neonatal Medicine

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Although low- and middle-income countries (LMICs) shoulder 90 % of the neonatal encephalopathy (NE) burden, there is very little evidence base for prevention or management of this condition in these settings. A variety of antenatal factors including socio-economic deprivation, undernutrition and sub optimal antenatal and intrapartum care increase the risk of NE, although little is known about the underlying mechanisms. Implementing interventions based on the evidence from high-income countries to LMICs, may cause more harm than benefit as shown by the increased mortality and lack of neuroprotection with cooling therapy in the hypothermia for moderate or severe NE in low and middle-income countries (HELIX) trial. Pooled data from pilot trials suggest that erythropoietin monotherapy reduces death and disability in LMICs, but this needs further evaluation in clinical trials. Careful attention to supportive care, including avoiding hyperoxia, hypocarbia, hypoglycemia, and hyperthermia, are likely to improve outcomes until specific neuroprotective or neurorestorative therapies available.

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Section: Introductionmentioning

confidence: 99%

Need for more evidence in the prevention and management of perinatal asphyxia and neonatal encephalopathy in low and middle-income countries: A call for action

Krishnan

Kumar

Variane³

et al. 2021

Seminars in Fetal and Neonatal Medicine

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“…Enforced DNA repair is directly neuroprotective, thus demonstrating that DNA damage accumulation is a driver of neuronal cell death in target deprivation settings, perhaps occurring in ALS [ 13 , 47 ], rather than a consequence of dying neurons [ 48 ]. In clinical settings, cooling reduces DNA damage in infants with hypoxic ischemic encephalopathy [ 49 ]. We also found a downregulation of UCP3 in the skeletal muscle of SOD1 mice maintained at ambient temperature at 12 weeks of age, and a bolstering of UCP3 levels in SOD1 mice with intermittent cold acclimation.…”

Section: Discussionmentioning

confidence: 99%

Chronic Intermittent Mild Whole-Body Hypothermia Is Therapeutic in a Mouse Model of ALS

Martin

Niedzwiecki

Wong

2021

Cells

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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that causes motor neuron degeneration. There are no cures or effective treatments for ALS. Therapeutic hypothermia is effectively used clinically to mitigate mortality in patients with acute acquired brain injury and in surgical settings to minimize secondary brain injury. The efficacy of therapeutic hypothermia in chronic neurodegenerative disorders has not been examined. We tested the hypothesis that mild hypothermia/cold acclimation is therapeutic in a transgenic mouse model of ALS caused by expression of mutated human superoxide dismutase-1 gene. At presymptomatic stages of disease, body temperatures (oral and axial) of mutant male mice were persistently hyperthermic (38–38.5 °C) compared to littermate controls, but at end-stage disease mice were generally hypothermic (36–36.5 °C). Presymptomatic mutant mice (awake-freely moving) were acclimated to systemic mild hypothermia using an environmentally controlled chamber (12 h-on/12-off or 24 h-on/24 h-off) to lower body temperature (1–3 °C). Cooled ALS mice showed a significant delay in disease onset (103–112 days) compared to normothermia mice (80–90 days) and exhibited significant attenuation of functional decline in motor performance. Cooled mice examined at 80 days had reduced motor neuron loss, mitochondrial swelling, and spinal cord inflammation compared to non-cooled mice. Cooling attenuated the loss of heat-shock protein 70, mitochondrial uncoupling protein-3, and sumoylated-1 (SUMO1)-conjugated proteins in skeletal muscle and disengaged the mitochondrial permeability transition pore. Cooled ALS mice had a significant extension of lifespan (148 ± 7 days) compared to normothermic mice (135 ± 4 days). Thus, intermittent systemic mild hypothermia is therapeutic in mouse ALS with protective effects manifested within the CNS and skeletal muscle that target mitochondria.

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“…The mechanism is reduction of cerebral metabolism and prevention of edema HIE. 6 Inadvertent excessive cooling (cold-injury syndrome) may occur during therapeutic hypothermia and may be due to inadequate monitoring, inexperienced staff or nonservo-controlled cooling systems. Asphyxiated newborns with HIE per se are known to have impaired thermoregulation.…”

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confidence: 99%

Neurological assessment and immediate outcome of newborns treated with therapeutic hypothermia at tertiary care hospital of southern Rajasthan-a randomized control trial

Goyal¹,

Sanadhya²,

Mehrotra³

et al. 2021

Int J Contemp Pediatr

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Background: Therapeutic hypothermia (TH) is standard-of-care for infants with moderate and severe HIE in developed countries; TH has been shown to decrease the risk of brain injury in asphyxiated newborns. Observations were like: 1) Asses morbidity and mortality in neonates with moderate and severe birth asphyxia treated with TH and 2) Asses neurological outcome in neonates.Methods: A RCT was done in NICU of Balchikitsalaya, RNTMC, Udaipur. Phase changing material, FS 21, FS 29 used to provide TH for 72 hours, started within 6 hours of birth and neurological outcome was assessed.Results: Total 60 neonates were enrolled 30 cases given TH and 30 control not given TH. Neurological assessment on basis of Thompson scoring, done on admission, 24, 48, 72 and 96 hours for both groups. At 48 hours, mean score in controls 14.5±1.67 and cases 11.47±2.34 (p<0.05). At discharge, mean score for controls was 11.31±3.67 and for cases was 5.24±2.72 (p<0.005). Mortality was 4 (13.3%) in cases and 11 (36.7%) in control group. Among 45 survivors, 25 (55.5%) required anticonvulsant at discharge; 15 from controls, 10 from cases group.Conclusions: There was significant decrease in mortality in birth asphyxia babies given TH as compared to babies not given TH. Also, significant improvement in Thompson score among the cooled neonates at and after 48 hours of age suggestive of better immediate neurological outcome in these babies. Anticonvulsant’s requirement was also significantly less in therapeutic hypothermia group.

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Effect of therapeutic hypothermia on chromosomal aberration in perinatal asphyxia

Cited by 5 publications

References 12 publications

Need for more evidence in the prevention and management of perinatal asphyxia and neonatal encephalopathy in low and middle-income countries: A call for action

Need for more evidence in the prevention and management of perinatal asphyxia and neonatal encephalopathy in low and middle-income countries: A call for action

Chronic Intermittent Mild Whole-Body Hypothermia Is Therapeutic in a Mouse Model of ALS

Neurological assessment and immediate outcome of newborns treated with therapeutic hypothermia at tertiary care hospital of southern Rajasthan-a randomized control trial

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