Asphyxia refers to impairment in the exchange
of respiratory gases, oxygen, and carbon dioxide
coupled with hypercapnia and consequent
acidosis and changes in cerebral blood flow.
The clinical correlates of this pathophysiological
definition of asphyxia have been the topic
of numerous studies but, as yet, there is no
The degree of asphyxia is best ascertained by measuring the amount of fetal acidosis determined by umbilical arterial blood. An umbilical arterial pH of less than 7.0 is seen in about 0.3% of deliveries.1 It indicates a severity of acidosis that places the fetus at risk for permanent neurological damage because of asphyxia. However, the outcome of infants with umbilical cord pH of less than 7.0 who required neonatal intensive care is relatively good. Eighty-one percent can be expected have a normal examination at discharge.1
This relative resistance of the brain to asphyxia is probably the consequence of a variety of fetal mechanisms that adapt to lack of oxygen and reduced cerebral blood flow. Also note that umbilical artery acidemia at birth is not invariably present in infants born with acute birth asphyxia.2
A number of other clinical and laboratory signs and symptoms suggest the presence of asphyxia. Alterations in fetal heart rate pattern have been studied as a diagnostic marker. Valentin and colleagues3 demonstrated that the most abnormal cord arterial pHs were associated with a pattern of reduced variability, reduced variability with late decelerations, or bradycardia with late decelerations. The passage of meconium and the presence of meconium-stained amniotic fluid also have been shown to indicate fetal distress and have been associated with fetal hypoxia, acidosis, and asphyxia.3 In the past, it was thought that a low Apgar score suggested asphyxia, but this has been debunked. Numerous studies have found low Apgar scores in infants with normal cord arterial pH and normal Apgar scores in asphyxiated infants.1,4,5
Umbilical cord lactate and serum concentrations of neuron-specific enolase have been suggested as markers for perinatal asphyxia and as an indication of the severity of hypoxic ischemic encephalopathy. These tests have not yet been found to have widespread clinical applicability.6,7
An abnormal neonatal course that includes features such as delayed or impaired respiration requiring resuscitative measures, a prolonged depressed Apgar score, seizures, hypotonia, and a bulging fontanel is the most important clue to the presence of perinatal asphyxia of sufficient severity to cause neurological deficits. Less obvious abnormalities are irritability, feeding difficulties, excessive jitters, or an abnormal cry.
In addition, clinical or laboratory evidence for asphyxial damage to organs other than the brain may be present. The multiple-organ dysfunction phenomenon is related to the diving reflex. This reflex, activated by asphyxia, consists in shunting blood from the skin and splanchnic area to the heart, adrenals, and brain, ostensibly to protect these vital organs from hypoxic-ischemic injury. In the series by Shah and colleagues,8 infants who had asphyxia injury to the brain showed evidence of dysfunction in at least 1 other organ.
The infant whose birth was complicated but whose neonatal period was uneventful is not at increased risk for neurological damage.9 The absence of the noted signs and symptoms in a youngster who subsequently presents with cerebral palsy points to a cause other than perinatal asphyxia.
Increased amounts of nucleated red blood cells (nRBCs) are frequently recorded in the infant with acute, subacute, or chronic asphyxia. There is a large overlap between nRBC values after acute and chronic asphyxia, however. Asphyxia of any duration does not invariably cause an increased nRBC count, and extreme increases can be found in the absence of asphyxia.10
Because cerebrospinal fluid (CSF) protein may be elevated after perinatal asphyxia, examination of CSF can provide some diagnostic evidence. In the term neonate, the mean CSF protein concentration is 90 mg/dL; values of more than 150 mg/dL are considered abnormal. In the premature neonate, the mean CSF protein concentration is 115 mg/dL.11 The presence of blood from any source raises the total protein by 1.5 mg/dL of fluid for every 1000 fresh red blood cells/µL.12 An elevation in the ratio of CSF lactate to pyruvate as well as a striking elevation of blood creatine kinase-BB isoenzyme persists in asphyxiated infants for several hours after normal oxygenation has been reestablished. However, a normal CSF does not exclude the possibility of perinatal asphyxia.
Neuroimaging studies are the best way to define the extent of asphyxial injury and to differentiate asphyxial injury from developmental or other acquired abnormalities. Ultrasonography, although easily performed, is of somewhat limited value in the evaluation of the asphyxiated infant. Although CT is useful for the detection of hemorrhage, difficulties are encountered in the CT analysis of parenchymal changes, and MRI is therefore the preferred imaging tool for delineating the extent and nature of asphyxial damage in the clinically stable term infant.
MRI performed on asphyxiated infants within the first 10 days of life demonstrates 3 patterns of damage.13,14 In one pattern seen in term infants, abnormalities are most commonly confined to the thalamus and basal ganglia. In one study,14 almost all infants with these lesions suffered an acute profound asphyxial insult. Mercuri and colleagues15 noted a stronger association between Apgar scores and basal ganglia lesions than with cord pH.
In another pattern, abnormalities are predominantly in the cerebral cortex and subcortical white matter. Periventricular white matter abnormalities are generally seen in preterm infants or in infants believed to have sustained in utero asphyxial damage before 34 to 35 weeks' gestation. Brainstem and cerebellar abnormalities are less common. In the series by Sie and coworkers,14 26% of infants who demonstrated periventricular leukomalacia (PVL) on MRI were born at term.
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