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  • Updated 01.30.2024
  • Released 02.03.1994
  • Expires For CME 01.30.2027

Perinatal hypoxic-ischemic encephalopathy


Key points

• Neonatal encephalopathy occurs in about three out of every 1000 term infants and can be caused by asphyxia, infection, endocrine/metabolic and genetic disorders, and unknown causes.

• Case control studies indicate that approximately 20% of cases of neonatal encephalopathy are caused by hypoxia-ischemia around the time of delivery and are diagnosed with hypoxic-ischemic encephalopathy (HIE).

• Brain magnetic resonance imaging (MRI) is useful for distinguishing hypoxic-ischemic encephalopathy from other causes of encephalopathy, as well as for prognosis.

• Randomized controlled trials showed that hypoxic-ischemic encephalopathy in term babies is treatable with moderate total body hypothermia at 33.5oC for 3 days if begun within 6 hours of birth.

• Therapeutic hypothermia has proved its efficacy on survival and severe disability, but there is still a need for new neuroprotective strategies to improve neurologic outcome.

Historical note and terminology

In 1862, the surgeon Little recognized a relationship between perinatal complications and cerebral palsy, and his report influenced the attitudes of clinicians over the next century who linked cerebral palsy to intrapartum events (82). However, Sigmund Freud studied the origins of cerebral palsy before he took up neuropsychiatry and concluded that the cause of cerebral palsy was more likely to be prenatal, and he observed that abnormal fetuses often went onto have abnormal deliveries (47). In 2006, the definition of cerebral palsy was refined as being a group of permanent disorders of the development of movement and posture that can be attributed to nonprogressive disturbances in the developing fetal or infant brain (109). Modern epidemiologic studies such as the NIH Perinatal Collaborative Study established that most cases of cerebral palsy are not caused by hypoxic-ischemic encephalopathy (HIE) at birth, but when hypoxic-ischemic encephalopathy is causative, the baby displays a group of signs that comprise neonatal encephalopathy (46). Sarnat and Sarnat were the first to describe the clinical and EEG features of mild, moderate, and severe encephalopathy associated with perinatal hypoxia-ischemia in term infants (111). The Sarnat scale for severity of encephalopathy is widely used in neonatal nurseries (13), and Levene and colleagues reported that the presence of moderate or severe encephalopathy in the newborn period is associated with neurologic handicap including cerebral palsy or death, but infants with mild encephalopathy generally escape without cerebral palsy (80). The presence of moderate or severe hypoxic-ischemic encephalopathy in the term infant is an essential link between exposure to asphyxia during or before the birth process and later disabilities, including cerebral palsy (06). Infants who were exposed to asphyxia but who do not manifest encephalopathy within several hours of exposure most likely will not have any permanent injury.

The concept of neonatal encephalopathy was examined in the landmark papers by Badawi and colleagues, which reported the first case-control study of all types of newborn encephalopathy, including hypoxic-ischemic encephalopathy in the Western Australian case-control study (12). This study showed the causes of newborn encephalopathy are heterogeneous, and approximately 70% are associated with antepartum factors. The remaining 30% of infants with encephalopathy had risk factors such as maternal pyrexia, persistent occipito-posterior position, and acute intrapartum events as well as evidence of hypoxia, but only 4% had evidence of hypoxia alone in the intrapartum period. For reasons not understood, there was a strong correlation between maternal thyroid disease and neonatal encephalopathy in infants. These data indicate that neonatal encephalopathy is a sign of brain dysfunction that can arise from a variety of infectious and noninfectious disorders in the mother or infant and is caused by intrapartum hypoxia in a minority of cases. Because hypoxic-ischemic encephalopathy is now treatable and can cause cerebral palsy and associated brain-based disabilities, guidelines for diagnosing hypoxic-ischemic encephalopathy have been developed by professional organizations, most notably by the American College of Obstetricians and Gynecologists (06) and the American Academy of Pediatrics (AAP). These guidelines are based in part on the massive data set provided by the National Perinatal Collaborative Study (46; 95).

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