Published online March 1, 2007
PEDIATRICS Vol. 119 No. 3 March 2007, pp. 615-617 (doi:10.1542/peds.2006-3650)
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COMMENTARY

The Use of Amplitude-Integrated Electroencephalography: Beware of Its Unintended Consequences

John M. Freeman, MD

John M. Freeman Pediatric Epilepsy Center, Department of Neurology, Johns Hopkins Medical Institutions and the Johns Hopkins Berman Bioethics Institute, Baltimore, Maryland

Abbreviations: EFM, electronic fetal monitoring • EEG, electroencephalography • aEEG, amplitude-integrated electroencephalography • ENS, electroencephalographically detected neonatal seizure

In the preface to the 2006 issue on brain monitoring in the neonate, White and Spitzer1 stated that continuous electroencephalogram monitoring "will substantially enhance our understanding of neonatal neurologic injury and markedly improve outcomes for all hospitalized newborn infants." However, they caution that "access to information often precedes the ability to use it wisely." In light of the experience of the obstetrical community with electronic fetal monitoring (EFM),2 widespread use of the new amplitude-integrated electroencephalography (aEEG) to diagnose and manage neonatal seizures should be implemented cautiously.


   ELECTRONIC FETAL HEART RATE MONITORING
TOP
 ELECTRONIC FETAL HEART RATE...
NEONATAL SEIZURES AND CONTINUOUS...
 CONCLUSIONS
 REFERENCES
 
EFM was introduced into widespread clinical practice in the early 1960s in an effort to identify a fetus undergoing stress or distress who might develop hypoxic-ischemic encephalopathy and subsequent cerebral palsy.3,4 At the time of its introduction, there were no controlled studies to show that it was preferable to auscultation. Subsequent studies and meta-analyses have shown that although the cesarean-section rate has increased by 40% since the introduction of EFM, the perinatal morbidity and mortality rates have not changed, nor has the incidence of subsequent cerebral palsy.5–7 However, EFM has resulted in a marked increase in maternal morbidity associated with the cesarean sections. Nelson7 noted that three fourths of children who developed cerebral palsy showed no abnormalities on fetal monitoring, and monitoring had a false-positive rate of 99.8%. There has also been a dramatic increase in the incidence of malpractice suits against obstetricians, often based on a retrospective interpretation of the monitoring strips. Knowing of the adverse outcome, lawyers and experts review the child's records and claim: "If only the delivery had been implemented earlier... ."

Despite many recent articles analyzing these effects,2 despite knowledge of fetal oxygen saturation,8 and despite the widespread conclusion that "[o]perative intervention based on fetal monitoring may do more harm than good,"9 EFM remains the standard of care.

Implementation of aEEG monitoring in nurseries to detect and manage neonatal seizures, without clear evidence of either benefit or effective therapy of the encephalopathy detected, may lead to similar adverse medical and legal outcomes.


   NEONATAL SEIZURES AND CONTINUOUS EEG MONITORING
TOP
 ELECTRONIC FETAL HEART RATE...
 NEONATAL SEIZURES AND CONTINUOUS...
CONCLUSIONS
 REFERENCES
 
"Seizures in the newborn are the most common and important sign of acute neonatal encephalopathy; are a major risk for death or subsequent neurologic disability; and of themselves may contribute to adverse neurodevelopmental outcome."10 Because clinical seizures may be missed or misinterpreted by the staff, and the interpretation of neonatal EEGs is labor intensive and requires considerable training, the equipment for the automated detection of spikes (aEEG) is increasingly used. The arguments for its use are similar to the arguments originally used for the implementation of EFM.

Although studies in infants have not disentangled the consequences of the underlying etiology of the seizures from the additional consequences of the seizures themselves, studies in animals11,12 and neonates13,14 have suggested that clinical seizures may (but only may) have adverse effects. The consequences of subclinical seizures and electroencephalographically detected neonatal seizures (ENSs) have not been studied, and their importance has not been established.

There is consensus that if treatment of clinical seizures is to be effective, early detection is imperative—and already possible using standard crib-side observations.14 aEEG only slightly enhances the identification of infants at risk for subclinical seizures.15 However, the occurrence of 2 recent international conferences on brain monitoring in the neonate and the presence of 3 companies that were selling aEEG machines at the recent Child Neurology Society meeting (October 2006) testify to the growing interest in this technology.

Recognizing the need to establish a safe and effective treatment for neonatal seizures, Clancy,10 writing for the Neurology Group on Neonatal Seizures, proposed a multicenter study of the efficacy of phenobarbital in the treatment of subclinical neonatal seizures and focused on newborns "at high risk for developing early subclinical electroencephalographically detected neonatal seizures (ENS)." It is acknowledged, however, that there are no data on intraobserver reliability in reading these studies; little evidence that the detected EEG abnormalities cause problems; and minimal evidence that treatment with phenobarbital or any other anticonvulsant is of more benefit than harm.15

As a study of the efficacy of phenobarbital on ENS, this multicenter project may be justifiable. However, the more widespread, routine use of this new, unproven, and unstandardized technology to detect and potentially treat clinical or subclinical neonatal seizures is fraught with hazard.

Neonatal seizures are virtually always the result of an existing or preexisting encephalopathy. The encephalopathy may be the result of clinical or subclinical infections in the mother or the infant or acute insults (such as trauma, bleeds, or strokes) and may, occasionally, be caused by fetal hypoxia or ischemia. Whatever the etiology, there is no clear evidence that subclinical seizures requiring aEEG detection cause damage above that caused by the underlying encephalopathic agent(s).14 There is also no clear evidence that anticonvulsant medications can effectively control the seizures and no evidence that such treatment decreases the subsequent sequelae such as cerebral palsy or retardation.15–17 However, there is evidence that the treatments themselves could have adverse effects on the central nervous system of the newborn.18

aEEG should not enjoy widespread use for the detection and treatment of neonatal seizures until it is:

  1. proven useful in reliably detecting abnormalities such as subtle (subclinical) seizures;
  2. shown that the test can be interpreted reliably and reproducibly by those who will use it;
  3. demonstrated that the seizures identified solely by aEEG lead to neurologic dysfunction; and
  4. shown that treatment prevents or ameliorates the dysfunction.


   CONCLUSIONS
TOP
 ELECTRONIC FETAL HEART RATE...
 NEONATAL SEIZURES AND CONTINUOUS...
 CONCLUSIONS
REFERENCES
 
aEEGs are increasingly used in nurseries to detect both seizures and subclinical seizures. It has been claimed that "every child admitted to a NICU with NE [neonatal encephalopathy] or seizures should be placed on continuous monitoring"19 despite the lack of evidence for the deleterious effects of subclinical seizures detected by ENS. Greisen20 pointed out that although subtle seizures and spikes are not normal, the benefits of intervention are unclear, and the additional benefits of monitoring are also unclear. Indeed, even the importance of interictal spikes remains in doubt.21–23

In light of the experience with the introduction of fetal monitoring and its medical-legal consequences, aEEG should be introduced into routine use with caution until evidence of its usefulness in seizure detection and the usefulness of seizure treatment is forthcoming.


   FOOTNOTES
 
Accepted Dec 21, 2006.

Address correspondence to John M. Freeman, MD, 1026 Rolandvue Rd, Towson, MD 21204. E-mail: jfreeman{at}jhmi.edu

The author has indicated he has no financial relationships relevant to this article to disclose.

Opinions expressed in these commentaries are those of the authors and not necessarily those of the American Academy of Pediatrics or its Committees.


   REFERENCES
TOP
 ELECTRONIC FETAL HEART RATE...
 NEONATAL SEIZURES AND CONTINUOUS...
 CONCLUSIONS
 REFERENCES
 

  1. Spitzer AR, White RD. Preface. Clin Perinatol. 2006;33 :3
  2. Green MF. Obstetricians still await a deus ex machina. N Engl J Med. 2006;355 :2247 –2248[Free Full Text]
  3. Hon EH. The electronic evaluation of the fetal heart rate: preliminary report. Am J Obstet Gynecol. 1958;75 :1215 –1230[Web of Science][Medline]
  4. Graham EM, Peterson SM, Christo DK, Fox HE. Intrapartum electronic fetal heart rate monitoring and the prevention of perinatal brain injury. Obstet Gynecol. 2006;108 :656 –666[CrossRef][Medline]
  5. Royal College of Obstetricians and Gynecologists. The Use of Electronic Fetal Monitoring: The Use and Interpretation of Cardiotocography in Intrapartum Fetal Surveillance. London, United Kingdom: RCOG Press; 2001
  6. Alfirevic Z, Devane D, Gyte GM. Continuous cardiotocography (CTG) as a form of electronic fetal monitoring (EFM) for fetal assessment during labour. Cochrane Database Syst Rev.2006;19 :CD006066
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  8. Bloom SL, Spong CY, Tham E, et al. Fetal pulse oximetry and cesarean delivery. N Engl J Med. 2006;355 :2195 –2202[Abstract/Free Full Text]
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  13. Perlman JM, Risser R. Can asphyxiated infants at risk for neonatal seizures be rapidly identified by current high-risk markers? Pediatrics. 1997;97 :456 –462[Web of Science]
  14. Shalak LF, Laptook AR, Velaphi SC, Perlman JM. Amplitude-integrated electroencephalography coupled with an early neurologic examination enhances prediction of term infants at risk for persistent encephalopathy? Pediatrics. 2003;111 :351 –357[Abstract/Free Full Text]
  15. Booth D, Evans DJ. Anticonvulsants for neonates with seizures. Cochrane Database Syst Rev. 2004;(4) :CD004218
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  17. Painter MJ, Scher MS, Stein AD, et al. Phenobarbital compared to phenytoin for treatment of neonatal seizures. N Engl J Med. 1999;341 :485 –489[Abstract/Free Full Text]
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  19. deVries LS, Toet MC. Amplitude integrated electroencephalography in the full-term newborn. Clin Perinatol. 2006;33 :619 –632[CrossRef][Web of Science][Medline]
  20. Greisen G. Brain monitoring in the neonate: the rationale. Clin Perinatol. 2006;33 :613 –618[CrossRef][Web of Science][Medline]
  21. Rogawski MA. Point-counterpoint: do interictal spikes trigger seizures or protect against them? Epilepsy Curr. 2006;6 :197 –198[CrossRef][Medline]
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PEDIATRICS (ISSN 1098-4275). ©2007 by the American Academy of Pediatrics

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