Anemia of Prematurity - Portal Neonatal

Hypoxic-Ischemic Encephalopathy
Last Updated: December 16, 2003
Synonyms and related keywords: HIE, perinatal asphyxia, birth asphyxia, neonatal asphyxia,
hypoxia, acidosis, ischemia
AUTHOR INFORMATION Section 1 of 10
Author: Tonse NK Raju, MD, DCH, Medical Officer, Pregnancy and Perinatology Branch, Center
for Developmental Biology and Perinatal Medicine, National Institutes of Child Health and Human
Development, National Institutes of Health
Tonse NK Raju, MD, DCH, is a member of the following medical societies: American Academy of
Pediatrics, American Association for the History of Medicine, American Medical Association,
American Pediatric Society, Society for Pediatric Research, and Society of Nuclear Medicine
Editor(s): Ted Rosenkrantz, MD, Head, Division of Neonatal Perinatal Medicine, Professor,
Department of Pediatrics, University of Connecticut Health Center; Robert Konop, PharmD,
Director, Clinical Account Management, Ancillary Care Management; Brian S Carter, MD,
Associate Director, Associate Professor, Department of Pediatrics, Division of Neonatology,
Vanderbilt University Medical Center and Gateway Medical Center; Carol L Wagner, MD,
Associate Professor, Department of Pediatrics, Division of Neonatology, Medical University of
South Carolina; and Neil N Finer, MD, Director, Division of Neonatology, Professor, Department
of Pediatrics, University of California at San Diego
INTRODUCTION Section 2 of 10
Background: In spite of major advances in monitoring technology and knowledge of fetal and
neonatal pathologies, perinatal asphyxia or, more appropriately, hypoxic-ischemic encephalopathy
(HIE), remains a serious condition, causing significant mortality and long-term morbidity.
HIE is an acquired syndrome characterized by clinical and laboratory evidence of acute brain injury
due to asphyxia (ie, hypoxia, acidosis). The American Academy of Pediatrics (AAP) and American
College of Obstetrics and Gynecology (ACOG) have published guidelines to assist in the diagnosis
of HIE (see History).
Pathophysiology: Brain hypoxia and ischemia from systemic hypoxemia and reduced cerebral
blood flow (CBF) are the primary triggering events for HIE. In this regard, HIE is similar to stroke
syndromes in adults, except that in neonates, the pathology is more generalized and the causes
are different. Initial compensatory adjustments, which include hypoxia (drop in partial pressure of
oxygen [PO2]) and hypercapnia (increased partial pressure of carbon dioxide [PCO2]), are
important and powerful stimuli, increasing CBF and thus oxygen delivery. During the early phase of
shock, the cardiac output is redistributed and the systemic BP increases (due to increased
epinephrine release) to maintain CBF.
Cerebral autoregulation of CBF maintains brain perfusion (for awhile) in spite of an initial drop in
the mean BP. In experimental animals, CBF autoregulation has been shown to be intact in
hypotension. However, the range of BP within which CBF is maintained is unknown for human
infants. This range is likely to be narrower and set at lower limits than the adult range (ie, 60-100
mm Hg).
With prolonged asphyxia, the early compensatory adjustments fail; CBF may become "pressurepassive,"
at which time brain perfusion is dependent on systemic BP. As BP falls, CBF falls below
critical levels and brain hypoxia occurs. This results in intracellular energy failure. During the early
phases of brain injury, brain temperature drops and local release of the neurotransmitter GABA
increases; these changes reduce cerebral oxygen demand, transiently minimizing the impact of
asphyxia.