Skip to main content

Advertisement

Log in

Treatment of hypoxic-ischemic encephalopathy in newborns

  • Published:
Current Treatment Options in Neurology Aims and scope Submit manuscript

Opinion statement

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Miller SP, Latal B, Clark H, et al.: Clinical signs predict 30-month neurodevelopmental outcome after neonatal encephalopathy. Am J Obstet Gynecol 2004, 190:93–99.

    Article  PubMed  Google Scholar 

  2. Wirrell EC, Armstrong EA, Osman LD, et al.: Prolonged seizures exacerbate perinatal hypoxic-ischemic brain damage. Pediatr Res 2001, 50:445–454.

    Article  PubMed  CAS  Google Scholar 

  3. Dzhala V, Ben-Ari Y, Khazipov R: Seizures accelerate anoxia-induced neuronal death in the neonatal rat hippocampus. Ann Neurol 2000, 48:632–640.

    Article  PubMed  CAS  Google Scholar 

  4. Miller SP, Weiss J, Barnwell A, et al.: Seizure-associated brain injury in term newborns with perinatal asphyxia. Neurology 2002, 58:542–548.

    PubMed  CAS  Google Scholar 

  5. Pressler RM, Boylan GB, Morton M, et al.: Early serial EEG in hypoxic ischaemic encephalopathy. Clin Neurophysiol 2001, 112:31–37.

    Article  PubMed  CAS  Google Scholar 

  6. Zeinstra E, Fock JM, Begeer JH, et al.: The prognostic value of serial EEG recordings following acute neonatal asphyxia in full-term infants. Eur J Paediatr Neurol 2001, 5:155–160.

    Article  PubMed  CAS  Google Scholar 

  7. de Vries LS, Toet MC: Amplitude integrated electroencephalography in the full-term newborn. Clin Perinatol 2006, 33:619–632, vi.

    Article  PubMed  Google Scholar 

  8. Barkovich AJ: MR imaging of the neonatal brain. Neuroimaging Clin N Am 2006, 16:117–135, viii–ix.

    Article  PubMed  CAS  Google Scholar 

  9. Barkovich AJ, Miller SP, Bartha A, et al.: MR imaging, MR spectroscopy, and diffusion tensor imaging of sequential studies in neonates with encephalopathy. AJNR Am J Neuroradiol 2006, 27:533–547.

    PubMed  CAS  Google Scholar 

  10. Roland EH, Poskitt K, Rodriguez E, et al.: Perinatal hypoxic-ischemic thalamic injury: clinical features and neuroimaging. Ann Neurol 1998, 44:161–166.

    Article  PubMed  CAS  Google Scholar 

  11. Erdogan N: Parasagittal injury in infants with hypoxic-ischemic encephalopathy. J Child Neurol 2001, 16:299–300.

    Article  PubMed  CAS  Google Scholar 

  12. Ramaswamy V, Miller SP, Barkovich AJ, et al.: Perinatal stroke in term infants with neonatal encephalopathy. Neurology 2004, 62:2088–2091.

    PubMed  CAS  Google Scholar 

  13. Wu YW, Hamrick SE, Miller SP, et al.: Intraventricular hemorrhage in term neonates caused by sinovenous thrombosis. Ann Neurol 2003, 54:123–126.

    Article  PubMed  Google Scholar 

  14. Miller SP, Ramaswamy V, Michelson D, et al.: Patterns of brain injury in term neonatal encephalopathy. J Pediatr 2005, 146:453–460.

    Article  PubMed  Google Scholar 

  15. Rutherford MA, Pennock JM, Counsell SJ, et al.: Abnormal magnetic resonance signal in the internal capsule predicts poor neurodevelopmental outcome in infants with hypoxic-ischemic encephalopathy. Pediatrics 1998, 102:323–328.

    Article  PubMed  CAS  Google Scholar 

  16. Boichot C, Walker PM, Durand C, et al.: Term neonate prognoses after perinatal asphyxia: contributions of MR imaging, MR spectroscopy, relaxation times, and apparent diffusion coefficients. Radiology 2006, 239:839–848.

    Article  PubMed  Google Scholar 

  17. Rutherford MA, Pennock JM, Dubowitz LM: Cranial ultrasound and magnetic resonance imaging in hypoxic-ischaemic encephalopathy: a comparison with outcome. Dev Med Child Neurol 1994, 36:813–825.

    Article  PubMed  CAS  Google Scholar 

  18. McLean C, Ferriero D: Mechanisms of hypoxic-ischemic injury in the term infant. Semin Perinatol 2004, 28:425–432.

    Article  PubMed  Google Scholar 

  19. Perlman JM: Intervention strategies for neonatal hypoxic-ischemic cerebral injury. Clin Ther 2006, 28:1353–1365.

    Article  PubMed  CAS  Google Scholar 

  20. Wyatt JS, Gluckman PD, Liu PY, et al.: Determinants of outcomes after head cooling for neonatal encephalopathy. Pediatrics 2007, 119:912–921.

    Article  PubMed  Google Scholar 

  21. Perlman JM: Hyperthermia in the delivery: potential impact on neonatal mortality and morbidity. Clin Perinatol 2006, 33:55–63, vi.

    Article  PubMed  Google Scholar 

  22. Kammersgaard LP, Jorgensen HS, Rungby JA, et al.: Admission body temperature predicts long-term mortality after acute stroke: the Copenhagen Stroke Study. Stroke 2002, 33:1759–1762.

    Article  PubMed  CAS  Google Scholar 

  23. Yager JY, Armstrong EA, Jaharus C, et al.: Preventing hyperthermia decreases brain damage following neonatal hypoxic-ischemic seizures. Brain Res 2004, 1011:48–57.

    Article  PubMed  CAS  Google Scholar 

  24. Salhab WA, Wyckoff MH, Laptook AR, et al.: Initial hypoglycemia and neonatal brain injury in term infants with severe fetal acidemia. Pediatrics 2004, 114:361–366.

    Article  PubMed  Google Scholar 

  25. Yager JY: Hypoglycemic injury to the immature brain. Clin Perinatol 2002, 29:651–674, vi.

    Article  PubMed  Google Scholar 

  26. Vannucci RC, Towfighi J, Heitjan DF, et al.: Carbon dioxide protects the perinatal brain from hypoxic-ischemic damage: an experimental study in the immature rat. Pediatrics 1995, 95:868–874.

    PubMed  CAS  Google Scholar 

  27. Tan A, Schulze A, O’Donnell CP, et al.: Air versus oxygen for resuscitation of infants at birth. Cochrane Database Syst Rev 2005, CD002273.

  28. Draycott T, Sibanda T, Owen L, et al.: Does training in obstetric emergencies improve neonatal outcome? BJOG 2006, 113:177–182.

    Article  PubMed  Google Scholar 

  29. Kecskes Z, Healy G, Jensen A: Fluid restriction for term infants with hypoxic-ischaemic encephalopathy following perinatal asphyxia. Cochrane Database Syst Rev 2005, CD004337.

  30. Eicher DJ, Wagner CL, Katikaneni LP, et al.: Moderate hypothermia in neonatal encephalopathy: efficacy outcomes. Pediatr Neurol 2005, 32:11–17.

    Article  PubMed  Google Scholar 

  31. Eicher DJ, Wagner CL, Katikaneni LP, et al.: Moderate hypothermia in neonatal encephalopathy: safety outcomes. Pediatr Neurol 2005, 32:18–24.

    Article  PubMed  Google Scholar 

  32. Gluckman PD, Wyatt JS, Azzopardi D, et al.: Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet 2005, 365:663–670.

    PubMed  Google Scholar 

  33. Shankaran S, Laptook AR, Ehrenkranz RA, et al.: Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 2005, 353:1574–1584.

    Article  PubMed  CAS  Google Scholar 

  34. O’Brien FE, Iwata O, Thornton JS, et al.: Delayed whole-body cooling to 33 or 35 degrees C and the development of impaired energy generation consequential to transient cerebral hypoxia-ischemia in the newborn piglet. Pediatrics 2006, 117:1549–1559.

    Article  PubMed  Google Scholar 

  35. Iwata O, Iwata S, Thornton JS, et al.: “Therapeutic time window” duration decreases with increasing severity of cerebral hypoxia-ischaemia under normothermia and delayed hypothermia in newborn piglets. Brain Res 2007, 1154:173–180.

    Article  PubMed  CAS  Google Scholar 

  36. Iwata O, Thornton JS, Sellwood MW, et al.: Depth of delayed cooling alters neuroprotection pattern after hypoxia-ischemia. Ann Neurol 2005, 58:75–87.

    Article  PubMed  Google Scholar 

  37. Clancy RR: Prolonged electroencephalogram monitoring for seizures and their treatment. Clin Perinatol 2006, 33:649–665, vi.

    Article  PubMed  Google Scholar 

  38. Painter MJ, Scher MS, Stein AD, et al.: Phenobarbital compared with phenytoin for the treatment of neonatal seizures. N Engl J Med 1999, 341:485–489.

    Article  PubMed  CAS  Google Scholar 

  39. Evans DJ, Levene MI: Anticonvulsants for preventing mortality and morbidity in full term newborns with perinatal asphyxia. Cochrane Database Syst Rev 2001, CD001240.

  40. Singh D, Kumar P, Narang A: A randomized controlled trial of phenobarbital in neonates with hypoxic ischemic encephalopathy. J Matern Fetal Neonatal Med 2005, 18:391–395.

    Article  PubMed  CAS  Google Scholar 

  41. Castro Conde JR, Hernandez Borges AA, Domenech Martinez E, et al.: Midazolam in neonatal seizures with no response to phenobarbital. Neurology 2005, 64:876–879.

    PubMed  CAS  Google Scholar 

  42. Gunes T, Ozturk MA, Koklu E, et al.: Effect of allopurinol supplementation on nitric oxide levels in asphyxiated newborns. Pediatr Neurol 2007, 36:17–24.

    Article  PubMed  Google Scholar 

  43. Benders MJ, Bos AF, Rademaker CM, et al.: Early postnatal allopurinol does not improve short term outcome after severe birth asphyxia. Arch Dis Child Fetal Neonatal Ed 2006, 91:F163–F165.

    Article  PubMed  CAS  Google Scholar 

  44. Hamrick SE, McQuillen PS, Jiang X, et al.: A role for hypoxia-inducible factor-1alpha in desferoxamine neuroprotection. Neurosci Lett 2005, 379:96–100.

    Article  PubMed  CAS  Google Scholar 

  45. Juul S: Erythropoietin in the central nervous system, and its use to prevent hypoxic-ischemic brain damage. Acta Paediatr Suppl 2002, 91:36–42.

    Article  PubMed  CAS  Google Scholar 

  46. Chang YS, Mu D, Wendland M, et al.: Erythropoietin improves functional and histological outcome in neonatal stroke. Pediatr Res 2005, 58:106–111.

    Article  PubMed  CAS  Google Scholar 

  47. Ichiba H, Tamai H, Negishi H, et al.: Randomized controlled trial of magnesium sulfate infusion for severe birth asphyxia. Pediatr Int 2002, 44:505–509.

    Article  PubMed  CAS  Google Scholar 

  48. Liu Y, Barks JD, Xu G, et al.: Topiramate extends the therapeutic window for hypothermia-mediated neuroprotection after stroke in neonatal rats. Stroke 2004, 35:1460–1465.

    Article  PubMed  CAS  Google Scholar 

  49. Koh S, Jensen FE: Topiramate blocks perinatal hypoxia-induced seizures in rat pups. Ann Neurol 2001, 50:366–372.

    Article  PubMed  CAS  Google Scholar 

  50. Preckel B, Weber NC, Sanders RD, et al.: Molecular mechanisms transducing the anesthetic, analgesic, and organ-protective actions of xenon. Anesthesiology 2006, 105:187–197.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Donna M. Ferriero.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Glass, H.C., Ferriero, D.M. Treatment of hypoxic-ischemic encephalopathy in newborns. Curr Treat Options Neurol 9, 414–423 (2007). https://doi.org/10.1007/s11940-007-0043-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11940-007-0043-0

Keywords

Navigation