Neonatal hypoxic–ischemic encephalopathy: emerging therapeutic strategies based on pathophysiologic phases of the injury

Wang, Qiuli; Lv, Haiyan; Lu, Lixin; Ren, Pengshun; Li, Lianxiang

doi:10.1080/14767058.2018.1468881

Cited by 46 publications

(39 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Multicenter RCTs are investigation the neuroprotective effects of erythropoietin, allopurinol, xenon, melatonin, and topiramate when administrated alone or as adjuvants to TH [ 39 – 43 ]. Our survey found that 81% of the hospitals used one or more putative neuroprotective agents, including erythropoietin, ganglioside, rat nerve growth factor, citicoline, and cerebrolysin [ 44 – 48 ]. Clinical trials conducted in China and meta-analyses of these studies showed that ganglioside, the most commonly used agent in our survey, was safe and effective in reducing neurological sequelae of HIE [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Neonatal hypoxic-ischemic encephalopathy diagnosis and treatment: a National Survey in China

et al. 2021

View full text Add to dashboard Cite

Background Neonatal hypoxic-ischemic encephalopathy (HIE) affects as many as 100,000 infants each year in China. Therapeutic hypothermia reduces HIE related mortality and long-term neurodevelopmental disabilities. National guidelines for HIE management were published a decade ago. This study aimed to investigate the current status of HIE diagnosis and treatment in China. Method This prospective cross-sectional national survey used a questionnaire evaluating practices related to HIE management. Descriptive statistics and Chi-square or Fisher’s exact test were used, and a p-value of < 0.05 was considered significant. Results The 273 hospitals that completed the survey were located in 31 of the 34 provincial districts in China. Eighty-eight percent of the hospitals were Level III hospitals, and 74% treated 10 or more HIE cases annually. Awareness rates of the national guidelines for HIE diagnosis, HIE treatment, and therapeutic hypothermia protocol were 85, 63, and 78%, respectively. Neurological manifestations and blood gas were used as HIE diagnostic criteria by 96% (263/273) and 68% (186/273) of the hospitals, respectively. Therapeutic hypothermia was used in 54% (147/273) of hospitals. The percentage of general hospitals that implemented therapeutic hypothermia (43%, 71/165) was significantly lower than that in maternity and infant hospitals (67%, 49/73) (χ2 = 11.752, p = 0.001) and children’s hospitals (77%, 27/35) (χ2 = 13.446, p < 0.001). Reasons for not providing therapeutic hypothermia included reduction of HIE cases in recent years (39%), high cost of cooling devices and treatment (31%), lack of training (26%), and safety concerns (4%). Among the hospitals that provided therapeutic hypothermia, 27% (39/147) were in full compliance with the recommended protocol. Eighty-one percent (222/273) of the hospitals treated HIE infants with putative neuroprotective agents alone or in combination with cooling. Ninety-one percent of the hospitals had long-term neurodevelopmental follow-up programs for infants with HIE. Conclusions There is significant heterogeneity in HIE diagnosis and treatment in China. Therapeutic hypothermia has not become a standard of care for neonatal HIE nationwide. Unproven agents are widely used for HIE treatment. Nationwide standardization of HIE management and dissemination of therapeutic hypothermia represent the opportunities to reduce mortality and improve long-term neurodevelopmental outcomes of children affected by HIE.

show abstract

Section: Discussionmentioning

confidence: 99%

Neonatal hypoxic-ischemic encephalopathy diagnosis and treatment: a National Survey in China

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Multicenter RCTs are investigation the neuroprotective effects of erythropoietin, allopurinol, xenon, melatonin, and topiramate when administrated alone or as adjuvants to TH [39][40][41][42][43]. Our survey found that 81% of the hospitals used one or more putative neuroprotective agents, including erythropoietin, ganglioside, rat nerve growth factor, citicoline, and cerebrolysin [44][45][46][47][48]. Clinical trials conducted in China and meta-analyses of these studies showed that ganglioside, the most commonly used agent in our survey, was safe and effective in reducing neurological sequelae of HIE [45].…”

Section: Discussionmentioning

confidence: 99%

“…Most of the studies lack data on long-term follow-up. Rat nerve growth factor, citicoline, and cerebrolysin were mainly evaluated by pre-clinical investigations and limited clinical studies [46][47][48]. Their neuroprotective effect remains to be demonstrated by multicenter RCTs.…”

Section: Discussionmentioning

confidence: 99%

Neonatal Hypoxic-Ischemic Encephalopathy Diagnosis and Treatment: A National Survey in China

Wang

Zhang

Zhou

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Neonatal hypoxic-ischemic encephalopathy (HIE) affects as many as 100,000 infants each year in China. Therapeutic hypothermia reduces HIE related mortality and long-term neurodevelopmental disabilities. National guidelines for HIE management were published a decade ago. This study aimed to investigate the current status of HIE diagnosis and treatment in China. Method: This prospective cross-sectional national survey used a questionnaire evaluating practices related to HIE management. Descriptive statistics and Chi-square or Fisher's exact test were used, and a p-value of <0.05 was considered significant. Results: The 273 hospitals that completed the survey were located in 31 of the 34 provincial districts in China. Eighty-eight percent of the hospitals were Level III hospitals, and 74% treated ten or more HIE cases annually. Awareness rates of the national guidelines for HIE diagnosis, HIE treatment, and therapeutic hypothermia protocol were 85%, 63%, and 78%, respectively. Neurological manifestations and blood gas were used as HIE diagnostic criteria by 96% (263/273) and 68% (186/273) of the hospitals, respectively. Therapeutic hypothermia was used in 54% (147/273) of hospitals. The percentage of general hospitals that implemented therapeutic hypothermia (43%, 71/165) was significantly lower than that in maternity and infant hospitals (67%, 49/73) (χ2=11.752, p=0.001) and children’s hospitals (77%, 27/35) (χ2=13.446, p<0.001). Reasons for not providing therapeutic hypothermia included reduction of HIE cases in recent years (39%), high cost of cooling devices and treatment (31%), lack of training (26%), and safety concerns (4%). Among the hospitals that provided therapeutic hypothermia, 27% (39/147) were in full compliance with the recommended protocol. Eighty-one percent (222/273) of the hospitals treated HIE infants with putative neuroprotective agents alone or in combination with cooling. Ninety-one percent of the hospitals had long-term neurodevelopmental follow-up programs for infants with HIE. Conclusions: There is significant heterogeneity in HIE diagnosis and treatment in China. Therapeutic hypothermia has not become a standard of care for neonatal HIE nationwide. Unproven agents are widely used for HIE treatment. Nationwide standardization of HIE management and dissemination of therapeutic hypothermia represent the opportunities to reduce mortality and improve long-term neurodevelopmental outcomes of children affected by HIE.

show abstract

“…Conceptually, brain injury caused by HI can be described in three phases [ 51 ]. The initial phase (primary energy failure) during which there is a decreased supply of oxygen and brain cells switch to anaerobic metabolism, which generates lactate and much less adenosine triphosphate (ATP) per molecule of glucose.…”

Section: Pathophysiology Of Preterm Brain Injurymentioning

confidence: 99%

Preterm Brain Injury, Antenatal Triggers, and Therapeutics: Timing Is Key

Ophelders

Gussenhoven

Klein

et al. 2020

Cells

View full text Add to dashboard Cite

With a worldwide incidence of 15 million cases, preterm birth is a major contributor to neonatal mortality and morbidity, and concomitant social and economic burden Preterm infants are predisposed to life-long neurological disorders due to the immaturity of the brain. The risks are inversely proportional to maturity at birth. In the majority of extremely preterm infants (<28 weeks’ gestation), perinatal brain injury is associated with exposure to multiple inflammatory perinatal triggers that include antenatal infection (i.e., chorioamnionitis), hypoxia-ischemia, and various postnatal injurious triggers (i.e., oxidative stress, sepsis, mechanical ventilation, hemodynamic instability). These perinatal insults cause a self-perpetuating cascade of peripheral and cerebral inflammation that plays a critical role in the etiology of diffuse white and grey matter injuries that underlies a spectrum of connectivity deficits in survivors from extremely preterm birth. This review focuses on chorioamnionitis and hypoxia-ischemia, which are two important antenatal risk factors for preterm brain injury, and highlights the latest insights on its pathophysiology, potential treatment, and future perspectives to narrow the translational gap between preclinical research and clinical applications.

show abstract

Neonatal hypoxic–ischemic encephalopathy: emerging therapeutic strategies based on pathophysiologic phases of the injury

Cited by 46 publications

References 34 publications

Neonatal hypoxic-ischemic encephalopathy diagnosis and treatment: a National Survey in China

Neonatal hypoxic-ischemic encephalopathy diagnosis and treatment: a National Survey in China

Neonatal Hypoxic-Ischemic Encephalopathy Diagnosis and Treatment: A National Survey in China

Preterm Brain Injury, Antenatal Triggers, and Therapeutics: Timing Is Key

Contact Info

Product

Resources

About