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Etiology and pathogenesis of neonatal encephalopathy

Sidhartha Tan, MD
Yvonne Wu, MD, MPH
Section Editors
Douglas R Nordli, Jr, MD
Leonard E Weisman, MD
Deputy Editor
John F Dashe, MD, PhD


Neonatal encephalopathy is a heterogeneous syndrome characterized by signs of central nervous system dysfunction in newborn infants. Clinical suspicion of neonatal encephalopathy should be considered in any infant exhibiting an abnormal level of consciousness, seizures, tone and reflex abnormalities, apnea, aspiration, feeding difficulties [1,2], and an abnormal hearing screen.

This topic will review the etiology and pathogenesis of neonatal encephalopathy. Other clinical aspects of this syndrome are discussed separately. (See "Clinical features, diagnosis, and treatment of neonatal encephalopathy".)


"Neonatal encephalopathy" has emerged as the preferred term to describe central nervous system dysfunction in the newborn period [2,3]. The American College of Obstetricians and Gynecologists (ACOG) describes neonatal encephalopathy as a clinically defined syndrome of disturbed neurologic function in the earliest days of life in an infant born at or beyond 35 weeks of gestation, manifested by a subnormal level of consciousness or seizures, and often accompanied by difficulty with initiating and maintaining respiration and depression of tone and reflexes [4].

The terminology does not imply a specific underlying pathophysiology, which is appropriate since the nature of brain injury causing neurologic impairment in a newborn is poorly understood. While neonatal encephalopathy was once automatically ascribed to hypoxia-ischemia [5], it is now known that hypoxia-ischemia is only one of many possible contributors to neonatal encephalopathy. Whether a particular newborn's encephalopathy can be attributed to hypoxic-ischemic brain injury is often unclear.

Some investigators require stringent criteria for using the term neonatal encephalopathy, such as two or more symptoms of encephalopathy lasting over 24 hours [6], while others require no more than a low five minute Apgar score [7]. However, the use of Apgar scores alone is problematic, as Apgar scores may be low due to maternal analgesia or prematurity, or can be normal in the presence of acute hypoxia-ischemic injury.

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Literature review current through: Nov 2017. | This topic last updated: Mar 10, 2016.
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