Published online October 1, 2008
PEDIATRICS Vol. 122 No. 4 October 2008, pp. 863-865 (doi:10.1542/peds.2008-1000)

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COMMENTARY

Amplitude-Integrated Electroencephalography in the Newborn: A Valuable Tool

Divyen K. Shah, MB, ChB^a, Linda S. de Vries, MD, PhD^b, Lena Hellström-Westas, MD, PhD^c, Mona C. Toet, MD, PhD^b and Terrie E. Inder, MD^a

^a Department of Pediatrics, Washington University, St Louis, Missouri
^b Department of Neonatology, University Medical Centre/Wilhelmina Children's Hospital, Utrecht, Netherlands
^c Department of Women's and Children's Health, Uppsala University Hospital, Uppsala, Sweden

Abbreviations: EEG, electroencephalography • aEEG, amplitude-integrated electroencephalography • CFM, cerebral function monitor • EFM, electronic fetal heart rate monitoring

The use of amplitude-integrated electroencephalography (aEEG) for research and clinical use in the newborn infant has increased over the last 2 decades. However, with this increased use, concerns have been expressed about (1) the accuracy and reliability of the interpretation of aEEG by neonatal clinicians and (2) the lack of evidence of benefit from aEEG monitoring for the infant.¹ As early as 1994, Greisen² noted that lack of knowledge of whether and when to act on the information obtained with aEEG, rather than the technology itself, limited the usefulness of this technique in the newborn. The aims of this commentary are to address these concerns by first reviewing the historical context in which the aEEG was developed and then summarizing current evidence on the use of aEEG in the newborn.

	HISTORICAL PERSPECTIVE: THE CEREBRAL FUNCTION MONITOR AND EARLY USE IN THE ADULT POPULATION

TOP HISTORICAL PERSPECTIVE: THE... aEEG AND NEONATAL ENCEPHALOPATHY aEEG AND NEONATAL SEIZURES ANALOGIES WITH CONTINUOUS... CONCLUSIONS REFERENCES

 
aEEG is not a new technology. The cerebral function monitor (CFM) was devised by Dr Douglas Maynard and its clinical potential was explored by Dr Pamela Prior in the 1960s as a means of monitoring cerebral function in adults undergoing bypass surgery and after resuscitation.^3,4 With its time-compressed output, the CFM provided a simpler and cheaper means of following trends in cerebral function in the ICU and the operating room without the need for experienced technicians for application, voluminous recordings, and expertise in interpretation for the, then, analog conventional EEG systems.

The electrode placement over the parietal areas (P3–P4 in the 10–20 system) was designed so as to be in close proximity to the vulnerable "watershed" regions of the brain in the border zones of arterial blood supply from all 3 cerebral arteries. This position also minimized artifacts from sweating, muscle activity, and eyelid movements. The system was designed to provide a sensitive output in the lower amplitude signals of 1 to 10 µV to focus on depressed cerebral activity, in addition to capturing high-amplitude levels of cerebral activity such as that seen during seizures. Hence, the amplitude scale in the original CFM was linear from 0 to 6 µV, semilogarithmic from 8 to 20 µV, and logarithmic at >25 µV.

Prior and Maynard divided the clinical applications of such neurophysiologic monitoring into 3 categories: (1) where it had been shown conclusively to reduce the risk of iatrogenic harm to an at-risk patient during elective procedures; (2) where it had provided additional useful information not obtainable by other means; and (3) where monitoring could have been of potential value but its advantages in terms of reduced morbidity or mortality remained unproven.⁵

	aEEG AND NEONATAL ENCEPHALOPATHY

TOP HISTORICAL PERSPECTIVE: THE... aEEG AND NEONATAL ENCEPHALOPATHY aEEG AND NEONATAL SEIZURES ANALOGIES WITH CONTINUOUS... CONCLUSIONS REFERENCES

 
Over the last 25 years, a considerable amount of work investigating the application of this technology in the newborn infant has been carried out. The aEEG pattern in the first 6 hours of life from term newborns with neonatal encephalopathy caused by hypoxia-ischemia has been shown to be strongly predictive of outcome.^6,7 A recent meta-analysis has confirmed the sensitivity of aEEG in predicting outcome after perinatal asphyxia.⁸ Additional studies have shown that the speed of recovery, as well as the severity of the abnormality, in the aEEG trace is prognostically valuable.^9,10 The predictive value of aEEG has been shown to extend to infants who were monitored after 24 hours of age and to infants with encephalopathy caused by conditions other than hypoxia-ischemia.¹¹ Also, the aEEG trace provides a permanent record of the "cerebral well-being" of the newborn.

Pattern-recognition as well as amplitude criteria have been used for the evaluation of aEEG after hypoxia-ischemia, and both methods seem valid for prediction, although pattern recognition may be more reliable.^12,13

	aEEG AND NEONATAL SEIZURES

TOP HISTORICAL PERSPECTIVE: THE... aEEG AND NEONATAL ENCEPHALOPATHY aEEG AND NEONATAL SEIZURES ANALOGIES WITH CONTINUOUS... CONCLUSIONS REFERENCES

 
Early work demonstrated that electrical seizure activity in at-risk infants could be identified by using the aEEG tracing.¹⁴ However, any system that uses a time-compressed output and a limited number of channels will not be able to detect all electrical seizure activity.¹⁵ The ideal system for monitoring electrical seizure activity should be sensitive in identifying the majority of electrical seizures. Although when using aEEG alone the sensitivity for detecting seizures offline may be low,¹⁶ particularly when used by inexperienced users with a short period of training,¹⁷ preliminary data suggest that the new digital bedside monitors using aEEG with the unprocessed EEG signal may be more sensitive and accurate when used by experienced users off-line for seizure detection in the term newborn.¹⁶ It appears that the regions conventionally used for aEEG electrode placement yield a high sensitivity (81%) for electrical seizure detection.¹⁸

Care of the newborn infant with seizures is challenging, with both underrecognition of "true" electroencephalographic seizures and overtreatment of abnormal movements thought to represent seizures.¹⁹ Few centers have the resources required for continuous video-EEG, the gold standard for monitoring electrical seizure activity. In the absence of continuous monitoring, a substantial "subclinical" seizure load as well as electrical-clinical uncoupling after pharmacologic treatment may go unrecognized.²⁰

Larger studies with bedside aEEG monitoring used "on-line" by less experienced neonatal clinicians around-the-clock are underway to determine the feasibility and impact of aEEG monitoring for electroencephalographic seizures in the NICU. Studies are also underway to test the accuracy of automated aEEG seizure-detection algorithms in the newborn.²¹ Clearly these studies will also lead to some interesting and important, albeit difficult, questions regarding the management of electroencephalographic seizures in the newborn infant.

	ANALOGIES WITH CONTINUOUS ELECTRONIC FETAL HEART RATE MONITORING

TOP HISTORICAL PERSPECTIVE: THE... aEEG AND NEONATAL ENCEPHALOPATHY aEEG AND NEONATAL SEIZURES ANALOGIES WITH CONTINUOUS... CONCLUSIONS REFERENCES

 
It is interesting to note that the earliest published use of the aEEG in the perinatal setting was a feasibility study on the use of aEEG to monitor fetal well-being.²² Analogies have been made recently between continuous electronic fetal heart rate monitoring (EFM) and the aEEG.¹ However, there are significant differences between the use of the aEEG in the newborn infant and intrapartum continuous EFM. The EEG signal that produces the aEEG pattern directly reflects electrocortical activity, a culmination of complex signals resulting in postsynaptic potentials. In contrast, the EFM, often representing the fetal heart rate in relation to uterine contraction activity, is a surrogate of fetal well-being and risk of cerebral injury. EFM abnormalities such as multiple decelerations or decreased heart rate variability have a low sensitivity (35%) for predicting cerebral palsy in a group at high risk.²³ In addition, EFM had a 99% false-positive rate for predicting cerebral palsy, even in high-risk patients. The use of EFM has not been shown to improve outcomes of perinatal mortality or cerebral palsy in term infants.²⁴ In contrast to this low sensitivity and high false-positive rate with EFM, the early use of aEEG has shown a sensitivity of 85% to 91% for predicting neurodevelopmental outcome in term newborn infants with neonatal encephalopathy⁷ and has been used in recruiting patients for study of therapeutic hypothermia.²⁵ The aEEG is intended to be used clinically to complement the neurologic examination, conventional EEG, and neuroimaging in evaluating the newborn, and not in isolation. Thus, emotionally charged comparisons between these 2 technologies regarding medicolegal implications have little or no substance.

	CONCLUSIONS

TOP HISTORICAL PERSPECTIVE: THE... aEEG AND NEONATAL ENCEPHALOPATHY aEEG AND NEONATAL SEIZURES ANALOGIES WITH CONTINUOUS... CONCLUSIONS REFERENCES

 
The aEEG was created to fulfill a need that existed for continuous cerebral function monitoring in vulnerable adults. This technique was subsequently adapted to the newborn requiring intensive care, for whom continuous monitoring of heart rate, respiration, oxygen saturation, and blood pressure were routine but continuous monitoring of brain function was not yet possible. The volume of research being conducted on application of aEEG in the newborn has increased exponentially over the last 2 decades and continues to be conducted in a systematic series of studies on the reliability, accuracy, and impact of aEEG monitoring. Modern digital monitors provide the unprocessed EEG signal as well as the aEEG from 1 or 2 channels. Obtaining separate-channel aEEG from each hemisphere may potentially give more information about unilateral cerebral injury,²⁶ and the unprocessed EEG signals used together with aEEG may improve electrical seizure detection.¹⁶

As physicians, our highest tenet is to first do no harm; hence we should be cautious of the unintended consequences when introducing any new technology into the nursery. However, inappropriate fears should not deter our desire to learn and progress in an attempt to identify the at-risk newborn infant and improve outcomes by reliable and appropriate monitoring of brain function to guide therapy.

	FOOTNOTES

 
Accepted Jun 18, 2008.

Address correspondence to Divyen K. Shah, MB, ChB, Washington University, Department of Pediatrics, 8th Floor, NW Tower, 1 Children's Place, St Louis, MO 63110. E-mail: shah_d{at}kids.wustl.edu

The authors have indicated they have no financial relationships relevant to this article to disclose.

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

	REFERENCES

TOP HISTORICAL PERSPECTIVE: THE... aEEG AND NEONATAL ENCEPHALOPATHY aEEG AND NEONATAL SEIZURES ANALOGIES WITH CONTINUOUS... CONCLUSIONS REFERENCES

 

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