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Updated: Jul 8, 2026
The Hypoxic Ischemic Encephalopathy Model of Perinatal Ischemia
Published on: November 19, 2008
Treatment of hypoxic-ischemic encephalopathy in newborns
Hannah C Glass1, Donna M Ferriero
1Donna M. Ferriero, MD University of California San Francisco, Neonatal Brain Disorders Center, Box 0663, 521 Parnassus Avenue, C-215, San Francisco, CA 94143, USA. ferrierod@neuropeds.ucsf.edu.
Insights
Therapeutic hypothermia shows promise in reducing death and disability from hypoxic-ischemic (HI) brain injury in newborns. Further research is needed to optimize seizure management and develop new neuroprotective therapies for neonatal encephalopathy.
Area of Science:
- Neonatal neurology
- Perinatal medicine
- Neurocritical care
Background:
- Hypoxic-ischemic (HI) brain injury is a leading cause of encephalopathy and seizures in term newborns.
- Diagnosis and timing of HI brain injury are challenging due to lack of definitive tests for birth asphyxia.
- Current management includes resuscitation, supportive care, and seizure treatment, but optimal strategies are debated.
Purpose of the Study:
- To review current understanding and management of hypoxic-ischemic brain injury in newborns.
- To highlight the potential of therapeutic hypothermia as a novel treatment.
- To identify the need for further clinical trials in neonatal encephalopathy and seizures.
Main Methods:
- Review of recent evidence on therapeutic hypothermia for neonatal hypoxic-ischemic brain injury.
- Discussion of current management practices for seizures in neonatal encephalopathy.
- Analysis of the limitations of existing treatments and the need for future research.
Main Results:
- Therapeutic hypothermia (head or whole-body cooling) initiated within 6 hours of birth may reduce death or moderate/severe disability.
- Phenobarbital, a common anti-seizure drug, has limited efficacy, and the role of treating subclinical seizures is uncertain.
- Preclinical studies suggest future therapies may combine neuroprotective and anti-seizure agents.
Conclusions:
- Therapeutic hypothermia is a promising intervention for hypoxic-ischemic brain injury that warrants consideration in clinical trials.
- There is a critical need for well-designed trials to address ongoing brain injury and optimize seizure treatment in neonates.
- Future treatments for neonatal encephalopathy and seizures are likely to involve novel combinations of neuroprotective and anticonvulsant agents.
Abstract:
Hypoxic-ischemic (HI) brain injury is the most common cause of encephalopathy and seizures in term newborn infants. There is no single, valid test for birth asphyxia leading to HI brain injury, and thus this disorder is often poorly characterized, and the timing and etiology of the injury can be difficult to ascertain. Optimal management of HI brain injury involves prompt resuscitation, careful supportive care including prevention of hyperthermia and hypoglycemia, and treatment of clinical and frequent or prolonged subclinical seizures. Recent evidence suggests that therapeutic hypothermia by selective head or whole-body cooling administered within 6 hours of birth reduces the incidence of death or moderate/severe disability at 12 to 22 months. Hypothermia is a promising new therapy that physicians should consider within the context of a registry or study. Optimal seizure treatment remains controversial because the most widely used drug, phenobarbital, has limited efficacy, and the value of monitoring and treating subclinical seizures is uncertain. There is compelling need for well-designed clinical trials to address treatment of ongoing brain injury in the setting of hypoxia-ischemia and seizures. Emerging evidence from preclinical studies suggests that future therapy for HI brain injury and neonatal encephalopathy will combine novel neuroprotective and anti-seizure agents. Pilot clinical trials of newer anticonvulsants are ongoing and will provide critical information for care of neonatal seizures.
