Original Article
Predictive Value of Early Amplitude-Integrated Electroencephalography for Later Diagnosed Cerebral White Matter Damage in Preterm Infants Juan Song1
Changlian Zhu1
Falin Xu1
Jiajia Guo1
1 Department of Pediatrics, The Third Affiliated Hospital of Zhengzhou
University, Zhengzhou, China Neuropediatrics 2014;45:314–320.
Abstract
Keywords
► white matter damage ► preterm infants ► amplitude-integrated electroencephalogram
Address for correspondence Juan Song, MD, Department of Pediatrics, The Third Affiliated Hospital of Zhengzhou University, 7 Kangfu Front Street, Zhengzhou 450000, China (e-mail: [email protected]).
Purpose The aim of the article is to assess the predictive value of amplitude-integrated electroencephalogram (aEEG) for cerebral white matter damage (WMD) in preterm infants. Patients and Methods Preterms 32 weeks’ gestational age (GA) born between March 2012 and December 2012 were enrolled. The aEEG patterns within 72 hours were classified and recorded to predict their neurodevelopmental prognosis and the predictive results were used to compare with the results by cerebral ultrasound examination. Neurobehavioral disorder (neonatal behavioral neurological assessment score < 35, dyskinesia or dysgnosia) or death was thought as poor neurodevelopmental prognosis. Psychomotor development index (PDI) or mental development index (MDI) 79 was regarded as dyskinesia or dysgnosia, respectively. Results Of the 63 preterms, 3.2% were born < 27 weeks’ gestation and 96.8% at 27 to 32 weeks’ gestation. The median GA was 29.3 weeks and the median birth weight was 1,030 g. On the basis of the aEEG results, normal, mildly abnormal, and severely abnormal cases were 10, 24, and 29; whereas determined by cerebral ultrasound, normal, mild, and severe cases were 17, 20, and 26, respectively. The aEEG degree showed significantly positive correlations with both WMD and poor neurodevelopmental prognosis (p < 0.01). Conclusion Abnormal aEEG of preterm infants within 72 hours after birth may imply WMD occurrence and poor neurodevelopmental prognosis.
Introduction On the basis of the development in perinatal care and severe treatment technology, the survival rates of preterm infants (born < 37 weeks of gestation) have dramatically increased. However, the development also results in a high prevalence of brain damage, commonly cerebral white matter damage (WMD) especially in very preterm infants
received August 17, 2013 accepted after revision April 22, 2014 published online July 8, 2014
Yanhua Zhang1
(VPT, born < 32 weeks of gestation) and extremely preterm infants (EPT, born < 27 weeks of gestation).1,2 The WMD in premature infants is associated with adverse neurodevelopmental deficits such as cerebral palsy (CP) and mental retardation. 3 About 60 to 100% of premature infants with characteristics of WMD can develop CP.4 Therefore, an early, accurate, and noninvasive diagnosis is of great value for the treatment and prognosis of WMD.
© 2014 Georg Thieme Verlag KG Stuttgart · New York
DOI http://dx.doi.org/ 10.1055/s-0034-1382823. ISSN 0174-304X.
Downloaded by: Collections and Technical Services Department. Copyrighted material.
314
aEEG Predicts WMD in Preterm Infants
Patients and Methods
to 10 days; and (3) severe cerebral WMD, which showed significant enhancement of echo, and periventricular leukomalacia or the decrease of cerebral white matter volume occurred after 3 to 4 weeks.
Amplitude-Integrated Electroencephalogram Degree Two-channel aEEG traces were recorded within 72 hours after birth with the cerebral function monitor (Nicolet One; Nicolet Biomedical Inc., Madison, Wisconsin, United States) using hydrogel electrodes, with standard electrode placement at Fp1–Fp2 regions on the scalp. Each recording lasted at least 4 hours to continuously monitor the background patterns and epileptiform activity. The speed of recording was regulated at 6 cm/h and the quality of the aEEG trace was monitored by a simultaneous continuous impedance trace, which was maintained at less than 20 kΩ. The aEEG tracings were assessed using the criteria by al Naqeeb et al,16 briefly as follows: (1) normal aEEG, normal amplitude as upper band > 10 µV and lower band > 5 µV; (2) moderately abnormal, mildly abnormal amplitude as upper band > 10 µV and lower band 5 µV, or normal amplitude with epileptiform activity; and (3) severely abnormal: severely abnormal amplitude as upper band < 10 µV and lower band < 5 µV or mildly abnormal amplitude with epileptiform activity. Epileptiform activity (seizures) can be identified on aEEG as a rapid rise in both the lower and upper band of the amplitude tracing.17 As for the sleep–wake cycling, a narrow bandwidth characterized wakefulness and active sleep, whereas a wider bandwidth denoted quiet sleep.18
Patients
Assessment of Neurobehavioral Development
In total, 63 preterm infants with gestational age (GA) < 32 weeks, admitted to the Third Affiliated Hospital of Zhengzhou University in 2 hours after birth, from March 2012 to December 2012, were recruited for this prospective study. The infants with intraventricular hemorrhage, congenital brain abnormality, chromosomal disease, or hereditary metabolic diseases were excluded according to the experimental design. The study was approved by the local Ethics Committee, and the informed consents were obtained from all the parents. The following neonatal factors were included: birth weight (BW), GA at birth, sex, mode of delivery, cord blood pH, Apgar score at 1 and 5 minutes, mean blood pressure (BP), mechanical ventilation, and the use of sedative or analgetic or anticonvulsant medications. Treatment with medications was always at the discretion of the clinician.
The Neonatal Behavioral Neurological Assessment (NBNA) score was used to assess the neurobehavioral development of preterm infants at a corrected GA of 40 weeks. The NBNA score < 35 could be regarded as suspicious neurobehavioral dysplasia. The psychomotor development index (PDI) and mental development index (MDI) were performed to evaluate the current developmental functioning of preterm infants after 3 months’ birth using child development center of China (CDCC) scale which was a modified version of the Bayley Scale special for Chinese infants. PDI 79 was defined as dyskinesia and MDI 79 as dysgnosia. Besides, the NBNA score < 35 or dyskinesia or dysgnosia was considered neurobehavioral dysplasia and meanwhile neurobehavioral disorder and death were both thought as poor neurodevelopmental prognosis.
Cerebral B Ultrasound
To evaluate the predictive values of aEEG in screening WMD, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of aEEG in screening WMD were calculated, and compared with other articles19–24 involving the predictive values of aEEG. Sensitivity and specificity was calculated using receiver–operating characteristic curves, which were generated by plotting true positive ratio (sensitivity) against the false positive ratio (1-specificity).
The regimen for cerebral ultrasound scans was performed on the 3rd day after birth and then once a week for the first 4 weeks. On the basis of the study by de Vries15 and our experiences, the WMD was classified into the following three categories: (1) no cerebral WMD, which showed no enhancement of the echo of cerebral white matter; (2) mild cerebral WMD, which performed transient and slight enhancement of the echo at the beginning, but decreased/disappeared after 7
315
Comparison of Predictive Effect of aEEG with Findings of Other Articles
Neuropediatrics
Vol. 45
No. 5/2014
Downloaded by: Collections and Technical Services Department. Copyrighted material.
As for the diagnosis of brain damage in preterm infants, electroencephalography (EEG) monitoring is a sensitive method.5,6 However, the most dominant feature of conventional EEG is discontinuity, which makes a “grading” and “severity-scoring” difficult in the VPT or EPT infants.7 Moreover, it is difficult to perform long-term monitoring using multichannel EEG recordings, especially in the first few days of life because of the fragile nature, especially in the early days after birth when the infants are usually in the critically unwell conditions.8,9 Limited channel amplitude-integrated electroencephalogram (aEEG) monitoring provides a derived parameter of EEG monitoring that can be performed to identify neurological injuries10,11 and continuously records valuable information about the background of cortical activity and occurrence of seizures within 72 hours after birth.12 The existing articles are commonly dealing with the assessment of aEEG in preterm infants with intraventricular hemorrhage during the early neonatal period, while the significance of aEEG in preterm infants with WMD during the early neonatal period has hardly been determined.13,14 To investigate the occurrence and severity of WMD, we performed two-channel aEEG on newborn preterm infants to explore the relationship between aEEG recording features and WMD severity using visual and quantitative analyses. We speculate that the features of two-channel aEEG of the preterm infants in an early time may have a predictive value for the occurrence of WMD in the following years, or even the severity of WMD.
Song et al.
aEEG Predicts WMD in Preterm Infants
Song et al.
Table 1 Characteristic of enrolled preterms Indexes
Values
Gestational age (wk)
29.3 2.35
26–27 (wk), n (%)
2 (3.2%)
27–32 (wk), n (%)
61 (96.8%)
Birth weight (g), mean SD
1,030 358
Male/female
1.9:1
Natural labor/cesarean delivery
3:7
Apgar 1 min, mean SD
5.7 2.8
Apgar 5 min, mean SD
8.0 1.5
Cord pH, mean SD
7.2 0.19
BP at 24 h (mm Hg)
(42 3.5)/(25 2.7)
Mechanical ventilation at 24 h, n (%)
25 (39.7)
Oxygen therapy using nCPAP, n (%)
30 (47.6%)
Oxygen therapy using nasal catheter
8 (12.7%)
Phenobarbital sodium within 24 h
3
Abbreviations: BP, blood pressure; nCPAP, nasal continuous positive airway pressure; pH, potential of hydrogen; SD, standard deviation.
Statistical Analysis Data of GA and BW were defined as mean standard deviation. All data were analyzed by SPSS 17.0 software (SPSS Inc., Chicago, Illinois, United States). The correlation of bidirectional orderly data was analyzed using chi-square test, Spearman correlation analysis, and Kendall tau-b test.
were born at 26 to 27 weeks’ gestation and 61 infants (96.8%) at 27 to 32 weeks’ gestation. The BW was 1,030 358 g, mean BP was (42 3.5)/(25 2.7) mm Hg and cord blood pH was 7.2 0.2. The Apgar score for 1 minute and 5 minute were 5.7 2.8 and 8.0 1.5, respectively. There were 25 infants undergoing mechanical ventilation, 30 receiving nasal continuous positive airway pressure (nCPAP) oxygen therapy and eight using oxygen therapy by nasal catheter after birth. Three infants with severe asphyxia (Apgar score of 1 minute < 3) were given phenobarbital sodium of 20 mg/kg/d by intravenous injection on the first day after birth, and then 5mg/kg/d for the following 3 to 5 days. Other characteristics at birth are all shown in ►Table 1.
Results of Cerebral B Ultrasound According to the mentioned standard of diagnosis, of the 63 infants, 17 cases had not developed cerebral WMD, 20 cases developed mild cerebral WMD, and 26 cases were severe cerebral WMD.
Determination of Amplitude-Integrated Electroencephalogram Degree On visual analysis of the aEEG, 10 cases (15.9%) were normal (►Fig. 1), 24 cases (38.1%) were mildly abnormal (►Fig. 2), and 29 cases (46.0%) were severely abnormal (►Figs. 3 and 4; ►Table 2). Among 24 cases with mildly abnormal aEEG, 22 cases were of mildly abnormal amplitude and 2 cases were of normal amplitude with epileptiform activity. Among the 29 cases with severely abnormal aEEG, mildly abnormal amplitude with epileptiform activity was found in 24 cases and severely abnormal amplitude with epileptiform activity was found in 5 cases.
Correlation between aEEG Degree and Grades of Cerebral WMD
Results Patients In total, 63 infants born at 26 to 32 (29.3 2.4) weeks’ gestation were enrolled in this study, and of them, 2 (3.2%)
The WMD in premature infants showed a significant positive correlation with aEEG degree (χ2 ¼ 12.42, p < 0.05; Spearman coefficient ¼ 0.35, p < 0.01; Kendall tau b ¼ 0.317, p < 0.01) (►Table 2). Meanwhile, in preterm infants with
Fig. 1 Gestational age of 31 weeks: normal amplitude-integrated electroencephalogram (discontinuous normal voltage, normal sleep–wake cycling, no burst suppression). Neuropediatrics
Vol. 45
No. 5/2014
Downloaded by: Collections and Technical Services Department. Copyrighted material.
316
Song et al.
Fig. 2 Gestational age of 29 weeks: mildly abnormal amplitude-integrated electroencephalogram (discontinuous voltage, no significant sleep– wake cycling, no burst suppression).
Fig. 3 Gestational age of 30 weeks: severely abnormal amplitude-integrated electroencephalogram (discontinuous voltage, loss of sleep–wake cycling, burst suppression).
severe WMD, we observed obviously discontinuous aEEG background, low border voltage (< 5 µV) and loss of sleep– wake cycling.
Correlation between aEEG Degree and Poor Neurodevelopmental Prognosis Of the 53 infants with abnormal aEEG, 33 cases (62.3%) had poor neurodevelopmental prognosis (25 dyskinesia, 6 dysgnosia, and 2 deaths) at the assessment at 3 months of age. As shown in ►Table 3, a significant positive correlation was observed between aEEG degree and grades of cerebral WMD in premature infants (χ2 ¼ 20.08, p < 0.01; Spearman coefficient ¼ 0.564, p < 0.01; Kendall tau-b ¼ 0.538, p < 0.01).
Comparison of Predictive Effect of aEEG with Findings of Other Articles On the basis of the current results, the sensitivity, specificity, PPV, and NPV of aEEG in screening WMD were 93.5, 41.2, 81.1,
and 70%, respectively. As shown in ►Table 4, the PPV, NPV, and the sensitivity of our experiment were similar with the referred articles, except the specificity, which was lower than other studies.19–25
Discussion WMD is one of the most common forms of cerebral damage and is reported to be highly related with preterm birth.3 Neuroimaging technologies, including ultrasound, magnetic resonance imaging, computed tomography, are now the most common diagnosis tools of CP in preterm infants, and also the primary tools for the examination of early changes in white matter. However, the preterm infants are special groups of patients who are immature and vulnerable in many aspects, such as immunity. Therefore, it is not suitable for them to accept the detection conducted by the instruments in fixed position, especially in the early days after birth. Recently, aEEG has been successfully applied to monitor and treat Neuropediatrics
Vol. 45
No. 5/2014
317
Downloaded by: Collections and Technical Services Department. Copyrighted material.
aEEG Predicts WMD in Preterm Infants
aEEG Predicts WMD in Preterm Infants
Song et al.
Fig. 4 Gestational age of 29 weeks: severely abnormal amplitude-integrated electroencephalogram (discontinuous voltage, loss of sleep–wake cycling, burst suppression).
encephalopathic infants at risk for WMD because of its noninvasive property, easy operation, advantages of continuous monitoring, and visual interpretation.25–27 In this study, aEEG was employed to examine the WMD in 63 preterm infants born before GA of 32 weeks, and investigate the relationship of aEEG degree and WMD grade, further supporting evidence for the prognosis and intervention treatment value of aEEG. As expected, we found that aEEG degree of abnormality could indicate the severity of WMD compared with the diagnosis by ultrasound, and could also be used as predictive and prognostic tool in preterm infants. For more than three decades, aEEG has been widely used to clarify the normal or abnormal brain activity in both full-term and preterm infants.18,28 Meanwhile, aEEG has been reported having a predictive value for brain damage, especially in the setting of preterm brain damage and intraventricular hemorrhage.17 It has been proven that some types of background activity patterns, the loss of a sleep–wake cycle, and seizure activity are related to the onset of early complications of encephalopathy such as intraventricular hemorrhage with intraparenchymal hemorrhage and periventricular leukomalacia.29 However, there is no systemic evaluation for the predictive value of aEEG degree of abnormality in WMD. In our study, we found that the aEEG degree of abnormality was positively related with the severity of WMD in preterm infants born less than 32 weeks’ gestation. Besides, patients with the abnormal aEEG pattern accompanied by epileptiform activity might develop severe WMD, according to our
data, 93.5% patients with epileptiform activity developed severe WMD. Consistent with our results, many authors have demonstrated that aEEG pattern has high values in predicting the severity of brain damage.30,31 Therefore, it can be concluded that epileptiform activity in aEEG-pattern seems to be a strong predictor for the occurrence of severe WMD in the following days. In addition, recent studies have shown that an aEEG performed in the early hours or during the first days of life can predict the neurobehavioral development of preterm infants at 2 to 3 years.9 As reported, discontinuous background is associated with low GA, and the continuity < 80% at the 10 µV level was a sensitive and specific marker of poor short-term outcome, whereas continuous low voltage (< 4 µV) can predict adverse developmental outcome.32 Also, noticeable differences in sleep–wake cycling, such as a shorter time of onset and increased duration of active sleep, can all provide prognostic value of adverse developmental outcome.33 A recent study has also shown that electrographic epileptiform activity in the first week of life correlate with adverse outcomes.34 In our study, the abnormal aEEG pattern in premature infants showed significantly positive relationship with poor neurodevelopmental prognosis (25 dyskinesia, 6 dysgnosia, and 2 deaths) as a long-term outcome. The abnormal aEEG pattern occurred in our study included discontinuous background, lower border voltage (< 5 µV), loss of sleep–wake cycling, and even epileptiform activity. The coincident conclusion points out that the epileptiform
Table 2 The correlation between aEEG and grade of cerebral white matter damage Cases
No cerebral white matter damage
Mild cerebral white matter damage
Severe cerebral white matter damage
aEEG normal
10
7
2
1
aEEG mildly abnormal
24
6
8
10
aEEG severely abnormal
29
4
10
15
Abbreviation: aEEG, amplitude-integrated electroencephalogram. Neuropediatrics
Vol. 45
No. 5/2014
Downloaded by: Collections and Technical Services Department. Copyrighted material.
318
aEEG Predicts WMD in Preterm Infants
Song et al.
319
Table 3 The correlation between aEEG and poor neurodevelopmental prognosis Cases
Neuronal dysplasia
Normal neural development
aEEG normal
10
1
9
aEEG mildly abnormal
24
9
15
aEEG severely abnormal
29
24
5
Abbreviation: aEEG, amplitude-integrated electroencephalogram.
Study references
N
PPV (%)
NPV (%)
Sensitivity (%)
Specificity (%)
Shany et al19
39
69
100
100
87
Hellström-Westas et al20
47
86
96
95
89
34
84
92
94
79
56
77
90
93
70
68
86
91
91
86
15
73
91
79
89
160
88
91
93
85
63
81
70
93
41
Eken et al
21
al Naqeeb et al16 Toet et al
22
Shalak et al
23
van Rooij et al Our study
24
Abbreviations: NPV, negative predictive value; PPV, positive predictive value.
activity caught by aEEG in the first few days after birth might mean a poor neurobehavioral prognosis that needs consideration of special intervention. As a result, aEEG pattern of preterm infants in the first days after birth can supply some predictive information for the risk of developing brain damage in the following days and neurobehavioral development in a long period. ter Horst et al have demonstrated that low-voltage patterns within the first 48 hours after admission are predictive of a poor neurological outcome or death.12 Many studies devote their effort on explaining the predictive value of aEEG for neonatal encephalopathy.8,9,19 As shown in ►Table 4, the PPV and NPV of aEEG in our study were 81.1 and 70%, respectively, and the predictive values obtained by different groups are very similar.19–25 A recent study has shown that the combination of early aEEG and clinical examination within the first 12 hours of birth can increase the PPV and specificity compared with either method alone.23 An accurate predictive value can help the physicians to understand the progress of brain damage more easily, and make a quick determination of pharmacological intervention and personalized treatment programs. There are several limitations in this study, such as small sample size and short follow-up time. Besides, the selective bias for hospital from the parents may affect the strength of these conclusions, for example, mothers usually choose the most powerful hospital for such serious diseases. Thus, the patient distribution will be unbalanced among the hospital in Zhengzhou. Therefore, further studies focusing on the correlation between aEEG dynamic monitoring and WMD in large cohort of subjects are recommended, as well as a long-term follow-up time. Meanwhile, further research is in great need
to clarify the accurate relationship between aEEG and WMD, especially the precise predictive value of aEEG for WMD. In conclusion, abnormal aEEG of preterm infants within 72 hours after birth may imply damage in white matter and predict poor neurodevelopmental prognosis, including dyskinesia, dysgnosia, or even deaths. The epileptiform activity patter might indicate a severe neurodevelopmental prognosis. Further study can emphasize on the precise predictive value of aEEG on WMD in a large cohort of subjects with a long-time follow-up.
References 1 Wilson-Costello D, Friedman H, Minich N, Fanaroff AA, Hack M.
2
3
4
5
6
Improved survival rates with increased neurodevelopmental disability for extremely low birth weight infants in the 1990s. Pediatrics 2005;115(4):997–1003 Fellman V, Hellström-Westas L, Norman M, et al; EXPRESS Group. One-year survival of extremely preterm infants after active perinatal care in Sweden. JAMA 2009;301(21):2225–2233 Saliba E, Marret S. Cerebral white matter damage in the preterm infant: pathophysiology and risk factors. Semin Neonatol 2001; 6(2): 121–133 Leviton A, Paneth N. White matter damage in preterm newborns—an epidemiologic perspective. Early Hum Dev 1990; 24(1):1–22 Hellström-Westas L, Rosén I. Electroencephalography and brain damage in preterm infants. Early Hum Dev 2005; 81(3):255–261 Hayakawa M, Okumura A, Hayakawa F, et al. Background electroencephalographic (EEG) activities of very preterm infants born at less than 27 weeks gestation: a study on the degree of continuity. Arch Dis Child Fetal Neonatal Ed 2001;84(3):F163–F167 Neuropediatrics
Vol. 45
No. 5/2014
Downloaded by: Collections and Technical Services Department. Copyrighted material.
Table 4 Predictive values of background patterns in some studies
aEEG Predicts WMD in Preterm Infants
Song et al.
7 Klebermass K, Olischar M, Waldhoer T, Fuiko R, Pollak A, Weninger
8 9
10
11
12
13
14
15 16
17 18
19
20
21
M. Amplitude-integrated EEG pattern predicts further outcome in preterm infants. Pediatr Res 2011;70(1):102–108 Toet MC, Lemmers PM. Brain monitoring in neonates. Early Hum Dev 2009;85(2):77–84 Wikström S, Pupp IH, Rosén I, et al. Early single-channel aEEG/EEG predicts outcome in very preterm infants. Acta Paediatr 2012; 101(7):719–726 Bowen JR, Paradisis M, Shah D. Decreased aEEG continuity and baseline variability in the first 48 hours of life associated with poor short-term outcome in neonates born before 29 weeks gestation. Pediatr Res 2010;67(5):538–544 Toet MC, van Rooij LG, de Vries LS. The use of amplitude integrated electroencephalography for assessing neonatal neurologic injury. Clin Perinatol 2008;35(4):665–678, v ter Horst HJ, van Olffen M, Remmelts HJ, de Vries H, Bos AF. The prognostic value of amplitude integrated EEG in neonatal sepsis and/or meningitis. Acta Paediatr 2010;99(2):194–200 Wikström S. Background aEEG/EEG measures in very preterm infants: Relation to physiology and outcome. Uppsala, Sweden: Acta Universitatis Upsaliensis; 2011 Wikström S, Ley D, Hansen-Pupp I, Rosén I, Hellström-Westas L. Early amplitude-integrated EEG correlates with cord TNF-α and brain injury in very preterm infants. Acta Paediatr 2008;97(7): 915–919 de Vries LS. Neurological assessment of the preterm infant. Acta Paediatr 1996;85(7):765–771 al Naqeeb N, Edwards AD, Cowan FM, Azzopardi D. Assessment of neonatal encephalopathy by amplitude-integrated electroencephalography. Pediatrics 1999;103(6 Pt 1):1263–1271 Tao JD, Mathur AM. Using amplitude-integrated EEG in neonatal intensive care. J Perinatol 2010;30(Suppl):S73–S81 Thornberg E, Thiringer K. Normal pattern of the cerebral function monitor trace in term and preterm neonates. Acta Paediatr Scand 1990;79(1):20–25 Shany E, Goldstein E, Khvatskin S, et al. Predictive value of amplitude-integrated electroencephalography pattern and voltage in asphyxiated term infants. Pediatr Neurol 2006;35(5): 335–342 Hellström-Westas L, Rosén I, Svenningsen NW. Predictive value of early continuous amplitude integrated EEG recordings on outcome after severe birth asphyxia in full term infants. Arch Dis Child Fetal Neonatal Ed 1995;72(1):F34–F38 Eken P, Toet MC, Groenendaal F, de Vries LS. Predictive value of early neuroimaging, pulsed Doppler and neurophysiology in full
Neuropediatrics
Vol. 45
No. 5/2014
22
23
24
25
26
27
28 29
30 31
32
33
34
term infants with hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed 1995;73(2):F75–F80 Toet MC, Hellström-Westas L, Groenendaal F, Eken P, de Vries LS. Amplitude integrated EEG 3 and 6 hours after birth in full term neonates with hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed 1999;81(1):F19–F23 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(2):351–357 van Rooij LG, Toet MC, Osredkar D, van Huffelen AC, Groenendaal F, de Vries LS. Recovery of amplitude integrated electroencephalographic background patterns within 24 hours of perinatal asphyxia. Arch Dis Child Fetal Neonatal Ed 2005;90(3):F245–F251 Chalak LF, Sikes NC, Mason MJ, Kaiser JR. Low-voltage aEEG as predictor of intracranial hemorrhage in preterm infants. Pediatr Neurol 2011;44(5):364–369 Hallberg B, Grossmann K, Bartocci M, Blennow M. The prognostic value of early aEEG in asphyxiated infants undergoing systemic hypothermia treatment. Acta Paediatr 2010;99(4):531–536 Csekő AJ, Bangó M, Lakatos P, Kárdási J, Pusztai L, Szabó M. Accuracy of amplitude-integrated electroencephalography in the prediction of neurodevelopmental outcome in asphyxiated infants receiving hypothermia treatment. Acta Paediatr 2013;102(7):707–711 Viniker DA, Maynard DE, Scott DF. Cerebral function monitor studies in neonates. Clin Electroencephalogr 1984;15(4):185–192 El-Dib M, Chang T, Tsuchida TN, Clancy RR. Amplitude-integrated electroencephalography in neonates. Pediatr Neurol 2009;41(5): 315–326 Scoppa A, Casani A, Cocca F, et al. aEEG in preterm infants. J Matern Fetal Neonatal Med 2012;25(Suppl 4):139–140 Shah DK, Lavery S, Doyle LW, Wong C, McDougall P, Inder TE. Use of 2-channel bedside electroencephalogram monitoring in termborn encephalopathic infants related to cerebral injury defined by magnetic resonance imaging. Pediatrics 2006;118(1):47–55 Lamblin M-D, Walls Esquivel E, André M. The electroencephalogram of the full-term newborn: Review of normal features and hypoxic-ischemic encephalopathy patterns. Neurophysiol Clin 2013;43(5–6):267–287 Scher MS, Steppe DA, Beggarly ME, Salerno DG, Banks DL. Neonatal EEG-sleep disruption mimicking hypoxic-ischemic encephalopathy after intrapartum asphyxia. Sleep Med 2002;3(5):411–415 Shah DK, Zempel J, Barton T, Lukas K, Inder TE. Electrographic seizures in preterm infants during the first week of life are associated with cerebral injury. Pediatr Res 2010;67(1):102–106
Downloaded by: Collections and Technical Services Department. Copyrighted material.
320
Predictive Value of Early Amplitude-Integrated Electroencephalography for Later Diagnosed Cerebral White Matter Damage in Preterm Infants Juan Song1
Changlian Zhu1
Falin Xu1
Jiajia Guo1
1 Department of Pediatrics, The Third Affiliated Hospital of Zhengzhou
University, Zhengzhou, China Neuropediatrics 2014;45:314–320.
Abstract
Keywords
► white matter damage ► preterm infants ► amplitude-integrated electroencephalogram
Address for correspondence Juan Song, MD, Department of Pediatrics, The Third Affiliated Hospital of Zhengzhou University, 7 Kangfu Front Street, Zhengzhou 450000, China (e-mail: [email protected]).
Purpose The aim of the article is to assess the predictive value of amplitude-integrated electroencephalogram (aEEG) for cerebral white matter damage (WMD) in preterm infants. Patients and Methods Preterms 32 weeks’ gestational age (GA) born between March 2012 and December 2012 were enrolled. The aEEG patterns within 72 hours were classified and recorded to predict their neurodevelopmental prognosis and the predictive results were used to compare with the results by cerebral ultrasound examination. Neurobehavioral disorder (neonatal behavioral neurological assessment score < 35, dyskinesia or dysgnosia) or death was thought as poor neurodevelopmental prognosis. Psychomotor development index (PDI) or mental development index (MDI) 79 was regarded as dyskinesia or dysgnosia, respectively. Results Of the 63 preterms, 3.2% were born < 27 weeks’ gestation and 96.8% at 27 to 32 weeks’ gestation. The median GA was 29.3 weeks and the median birth weight was 1,030 g. On the basis of the aEEG results, normal, mildly abnormal, and severely abnormal cases were 10, 24, and 29; whereas determined by cerebral ultrasound, normal, mild, and severe cases were 17, 20, and 26, respectively. The aEEG degree showed significantly positive correlations with both WMD and poor neurodevelopmental prognosis (p < 0.01). Conclusion Abnormal aEEG of preterm infants within 72 hours after birth may imply WMD occurrence and poor neurodevelopmental prognosis.
Introduction On the basis of the development in perinatal care and severe treatment technology, the survival rates of preterm infants (born < 37 weeks of gestation) have dramatically increased. However, the development also results in a high prevalence of brain damage, commonly cerebral white matter damage (WMD) especially in very preterm infants
received August 17, 2013 accepted after revision April 22, 2014 published online July 8, 2014
Yanhua Zhang1
(VPT, born < 32 weeks of gestation) and extremely preterm infants (EPT, born < 27 weeks of gestation).1,2 The WMD in premature infants is associated with adverse neurodevelopmental deficits such as cerebral palsy (CP) and mental retardation. 3 About 60 to 100% of premature infants with characteristics of WMD can develop CP.4 Therefore, an early, accurate, and noninvasive diagnosis is of great value for the treatment and prognosis of WMD.
© 2014 Georg Thieme Verlag KG Stuttgart · New York
DOI http://dx.doi.org/ 10.1055/s-0034-1382823. ISSN 0174-304X.
Downloaded by: Collections and Technical Services Department. Copyrighted material.
314
aEEG Predicts WMD in Preterm Infants
Patients and Methods
to 10 days; and (3) severe cerebral WMD, which showed significant enhancement of echo, and periventricular leukomalacia or the decrease of cerebral white matter volume occurred after 3 to 4 weeks.
Amplitude-Integrated Electroencephalogram Degree Two-channel aEEG traces were recorded within 72 hours after birth with the cerebral function monitor (Nicolet One; Nicolet Biomedical Inc., Madison, Wisconsin, United States) using hydrogel electrodes, with standard electrode placement at Fp1–Fp2 regions on the scalp. Each recording lasted at least 4 hours to continuously monitor the background patterns and epileptiform activity. The speed of recording was regulated at 6 cm/h and the quality of the aEEG trace was monitored by a simultaneous continuous impedance trace, which was maintained at less than 20 kΩ. The aEEG tracings were assessed using the criteria by al Naqeeb et al,16 briefly as follows: (1) normal aEEG, normal amplitude as upper band > 10 µV and lower band > 5 µV; (2) moderately abnormal, mildly abnormal amplitude as upper band > 10 µV and lower band 5 µV, or normal amplitude with epileptiform activity; and (3) severely abnormal: severely abnormal amplitude as upper band < 10 µV and lower band < 5 µV or mildly abnormal amplitude with epileptiform activity. Epileptiform activity (seizures) can be identified on aEEG as a rapid rise in both the lower and upper band of the amplitude tracing.17 As for the sleep–wake cycling, a narrow bandwidth characterized wakefulness and active sleep, whereas a wider bandwidth denoted quiet sleep.18
Patients
Assessment of Neurobehavioral Development
In total, 63 preterm infants with gestational age (GA) < 32 weeks, admitted to the Third Affiliated Hospital of Zhengzhou University in 2 hours after birth, from March 2012 to December 2012, were recruited for this prospective study. The infants with intraventricular hemorrhage, congenital brain abnormality, chromosomal disease, or hereditary metabolic diseases were excluded according to the experimental design. The study was approved by the local Ethics Committee, and the informed consents were obtained from all the parents. The following neonatal factors were included: birth weight (BW), GA at birth, sex, mode of delivery, cord blood pH, Apgar score at 1 and 5 minutes, mean blood pressure (BP), mechanical ventilation, and the use of sedative or analgetic or anticonvulsant medications. Treatment with medications was always at the discretion of the clinician.
The Neonatal Behavioral Neurological Assessment (NBNA) score was used to assess the neurobehavioral development of preterm infants at a corrected GA of 40 weeks. The NBNA score < 35 could be regarded as suspicious neurobehavioral dysplasia. The psychomotor development index (PDI) and mental development index (MDI) were performed to evaluate the current developmental functioning of preterm infants after 3 months’ birth using child development center of China (CDCC) scale which was a modified version of the Bayley Scale special for Chinese infants. PDI 79 was defined as dyskinesia and MDI 79 as dysgnosia. Besides, the NBNA score < 35 or dyskinesia or dysgnosia was considered neurobehavioral dysplasia and meanwhile neurobehavioral disorder and death were both thought as poor neurodevelopmental prognosis.
Cerebral B Ultrasound
To evaluate the predictive values of aEEG in screening WMD, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of aEEG in screening WMD were calculated, and compared with other articles19–24 involving the predictive values of aEEG. Sensitivity and specificity was calculated using receiver–operating characteristic curves, which were generated by plotting true positive ratio (sensitivity) against the false positive ratio (1-specificity).
The regimen for cerebral ultrasound scans was performed on the 3rd day after birth and then once a week for the first 4 weeks. On the basis of the study by de Vries15 and our experiences, the WMD was classified into the following three categories: (1) no cerebral WMD, which showed no enhancement of the echo of cerebral white matter; (2) mild cerebral WMD, which performed transient and slight enhancement of the echo at the beginning, but decreased/disappeared after 7
315
Comparison of Predictive Effect of aEEG with Findings of Other Articles
Neuropediatrics
Vol. 45
No. 5/2014
Downloaded by: Collections and Technical Services Department. Copyrighted material.
As for the diagnosis of brain damage in preterm infants, electroencephalography (EEG) monitoring is a sensitive method.5,6 However, the most dominant feature of conventional EEG is discontinuity, which makes a “grading” and “severity-scoring” difficult in the VPT or EPT infants.7 Moreover, it is difficult to perform long-term monitoring using multichannel EEG recordings, especially in the first few days of life because of the fragile nature, especially in the early days after birth when the infants are usually in the critically unwell conditions.8,9 Limited channel amplitude-integrated electroencephalogram (aEEG) monitoring provides a derived parameter of EEG monitoring that can be performed to identify neurological injuries10,11 and continuously records valuable information about the background of cortical activity and occurrence of seizures within 72 hours after birth.12 The existing articles are commonly dealing with the assessment of aEEG in preterm infants with intraventricular hemorrhage during the early neonatal period, while the significance of aEEG in preterm infants with WMD during the early neonatal period has hardly been determined.13,14 To investigate the occurrence and severity of WMD, we performed two-channel aEEG on newborn preterm infants to explore the relationship between aEEG recording features and WMD severity using visual and quantitative analyses. We speculate that the features of two-channel aEEG of the preterm infants in an early time may have a predictive value for the occurrence of WMD in the following years, or even the severity of WMD.
Song et al.
aEEG Predicts WMD in Preterm Infants
Song et al.
Table 1 Characteristic of enrolled preterms Indexes
Values
Gestational age (wk)
29.3 2.35
26–27 (wk), n (%)
2 (3.2%)
27–32 (wk), n (%)
61 (96.8%)
Birth weight (g), mean SD
1,030 358
Male/female
1.9:1
Natural labor/cesarean delivery
3:7
Apgar 1 min, mean SD
5.7 2.8
Apgar 5 min, mean SD
8.0 1.5
Cord pH, mean SD
7.2 0.19
BP at 24 h (mm Hg)
(42 3.5)/(25 2.7)
Mechanical ventilation at 24 h, n (%)
25 (39.7)
Oxygen therapy using nCPAP, n (%)
30 (47.6%)
Oxygen therapy using nasal catheter
8 (12.7%)
Phenobarbital sodium within 24 h
3
Abbreviations: BP, blood pressure; nCPAP, nasal continuous positive airway pressure; pH, potential of hydrogen; SD, standard deviation.
Statistical Analysis Data of GA and BW were defined as mean standard deviation. All data were analyzed by SPSS 17.0 software (SPSS Inc., Chicago, Illinois, United States). The correlation of bidirectional orderly data was analyzed using chi-square test, Spearman correlation analysis, and Kendall tau-b test.
were born at 26 to 27 weeks’ gestation and 61 infants (96.8%) at 27 to 32 weeks’ gestation. The BW was 1,030 358 g, mean BP was (42 3.5)/(25 2.7) mm Hg and cord blood pH was 7.2 0.2. The Apgar score for 1 minute and 5 minute were 5.7 2.8 and 8.0 1.5, respectively. There were 25 infants undergoing mechanical ventilation, 30 receiving nasal continuous positive airway pressure (nCPAP) oxygen therapy and eight using oxygen therapy by nasal catheter after birth. Three infants with severe asphyxia (Apgar score of 1 minute < 3) were given phenobarbital sodium of 20 mg/kg/d by intravenous injection on the first day after birth, and then 5mg/kg/d for the following 3 to 5 days. Other characteristics at birth are all shown in ►Table 1.
Results of Cerebral B Ultrasound According to the mentioned standard of diagnosis, of the 63 infants, 17 cases had not developed cerebral WMD, 20 cases developed mild cerebral WMD, and 26 cases were severe cerebral WMD.
Determination of Amplitude-Integrated Electroencephalogram Degree On visual analysis of the aEEG, 10 cases (15.9%) were normal (►Fig. 1), 24 cases (38.1%) were mildly abnormal (►Fig. 2), and 29 cases (46.0%) were severely abnormal (►Figs. 3 and 4; ►Table 2). Among 24 cases with mildly abnormal aEEG, 22 cases were of mildly abnormal amplitude and 2 cases were of normal amplitude with epileptiform activity. Among the 29 cases with severely abnormal aEEG, mildly abnormal amplitude with epileptiform activity was found in 24 cases and severely abnormal amplitude with epileptiform activity was found in 5 cases.
Correlation between aEEG Degree and Grades of Cerebral WMD
Results Patients In total, 63 infants born at 26 to 32 (29.3 2.4) weeks’ gestation were enrolled in this study, and of them, 2 (3.2%)
The WMD in premature infants showed a significant positive correlation with aEEG degree (χ2 ¼ 12.42, p < 0.05; Spearman coefficient ¼ 0.35, p < 0.01; Kendall tau b ¼ 0.317, p < 0.01) (►Table 2). Meanwhile, in preterm infants with
Fig. 1 Gestational age of 31 weeks: normal amplitude-integrated electroencephalogram (discontinuous normal voltage, normal sleep–wake cycling, no burst suppression). Neuropediatrics
Vol. 45
No. 5/2014
Downloaded by: Collections and Technical Services Department. Copyrighted material.
316
Song et al.
Fig. 2 Gestational age of 29 weeks: mildly abnormal amplitude-integrated electroencephalogram (discontinuous voltage, no significant sleep– wake cycling, no burst suppression).
Fig. 3 Gestational age of 30 weeks: severely abnormal amplitude-integrated electroencephalogram (discontinuous voltage, loss of sleep–wake cycling, burst suppression).
severe WMD, we observed obviously discontinuous aEEG background, low border voltage (< 5 µV) and loss of sleep– wake cycling.
Correlation between aEEG Degree and Poor Neurodevelopmental Prognosis Of the 53 infants with abnormal aEEG, 33 cases (62.3%) had poor neurodevelopmental prognosis (25 dyskinesia, 6 dysgnosia, and 2 deaths) at the assessment at 3 months of age. As shown in ►Table 3, a significant positive correlation was observed between aEEG degree and grades of cerebral WMD in premature infants (χ2 ¼ 20.08, p < 0.01; Spearman coefficient ¼ 0.564, p < 0.01; Kendall tau-b ¼ 0.538, p < 0.01).
Comparison of Predictive Effect of aEEG with Findings of Other Articles On the basis of the current results, the sensitivity, specificity, PPV, and NPV of aEEG in screening WMD were 93.5, 41.2, 81.1,
and 70%, respectively. As shown in ►Table 4, the PPV, NPV, and the sensitivity of our experiment were similar with the referred articles, except the specificity, which was lower than other studies.19–25
Discussion WMD is one of the most common forms of cerebral damage and is reported to be highly related with preterm birth.3 Neuroimaging technologies, including ultrasound, magnetic resonance imaging, computed tomography, are now the most common diagnosis tools of CP in preterm infants, and also the primary tools for the examination of early changes in white matter. However, the preterm infants are special groups of patients who are immature and vulnerable in many aspects, such as immunity. Therefore, it is not suitable for them to accept the detection conducted by the instruments in fixed position, especially in the early days after birth. Recently, aEEG has been successfully applied to monitor and treat Neuropediatrics
Vol. 45
No. 5/2014
317
Downloaded by: Collections and Technical Services Department. Copyrighted material.
aEEG Predicts WMD in Preterm Infants
aEEG Predicts WMD in Preterm Infants
Song et al.
Fig. 4 Gestational age of 29 weeks: severely abnormal amplitude-integrated electroencephalogram (discontinuous voltage, loss of sleep–wake cycling, burst suppression).
encephalopathic infants at risk for WMD because of its noninvasive property, easy operation, advantages of continuous monitoring, and visual interpretation.25–27 In this study, aEEG was employed to examine the WMD in 63 preterm infants born before GA of 32 weeks, and investigate the relationship of aEEG degree and WMD grade, further supporting evidence for the prognosis and intervention treatment value of aEEG. As expected, we found that aEEG degree of abnormality could indicate the severity of WMD compared with the diagnosis by ultrasound, and could also be used as predictive and prognostic tool in preterm infants. For more than three decades, aEEG has been widely used to clarify the normal or abnormal brain activity in both full-term and preterm infants.18,28 Meanwhile, aEEG has been reported having a predictive value for brain damage, especially in the setting of preterm brain damage and intraventricular hemorrhage.17 It has been proven that some types of background activity patterns, the loss of a sleep–wake cycle, and seizure activity are related to the onset of early complications of encephalopathy such as intraventricular hemorrhage with intraparenchymal hemorrhage and periventricular leukomalacia.29 However, there is no systemic evaluation for the predictive value of aEEG degree of abnormality in WMD. In our study, we found that the aEEG degree of abnormality was positively related with the severity of WMD in preterm infants born less than 32 weeks’ gestation. Besides, patients with the abnormal aEEG pattern accompanied by epileptiform activity might develop severe WMD, according to our
data, 93.5% patients with epileptiform activity developed severe WMD. Consistent with our results, many authors have demonstrated that aEEG pattern has high values in predicting the severity of brain damage.30,31 Therefore, it can be concluded that epileptiform activity in aEEG-pattern seems to be a strong predictor for the occurrence of severe WMD in the following days. In addition, recent studies have shown that an aEEG performed in the early hours or during the first days of life can predict the neurobehavioral development of preterm infants at 2 to 3 years.9 As reported, discontinuous background is associated with low GA, and the continuity < 80% at the 10 µV level was a sensitive and specific marker of poor short-term outcome, whereas continuous low voltage (< 4 µV) can predict adverse developmental outcome.32 Also, noticeable differences in sleep–wake cycling, such as a shorter time of onset and increased duration of active sleep, can all provide prognostic value of adverse developmental outcome.33 A recent study has also shown that electrographic epileptiform activity in the first week of life correlate with adverse outcomes.34 In our study, the abnormal aEEG pattern in premature infants showed significantly positive relationship with poor neurodevelopmental prognosis (25 dyskinesia, 6 dysgnosia, and 2 deaths) as a long-term outcome. The abnormal aEEG pattern occurred in our study included discontinuous background, lower border voltage (< 5 µV), loss of sleep–wake cycling, and even epileptiform activity. The coincident conclusion points out that the epileptiform
Table 2 The correlation between aEEG and grade of cerebral white matter damage Cases
No cerebral white matter damage
Mild cerebral white matter damage
Severe cerebral white matter damage
aEEG normal
10
7
2
1
aEEG mildly abnormal
24
6
8
10
aEEG severely abnormal
29
4
10
15
Abbreviation: aEEG, amplitude-integrated electroencephalogram. Neuropediatrics
Vol. 45
No. 5/2014
Downloaded by: Collections and Technical Services Department. Copyrighted material.
318
aEEG Predicts WMD in Preterm Infants
Song et al.
319
Table 3 The correlation between aEEG and poor neurodevelopmental prognosis Cases
Neuronal dysplasia
Normal neural development
aEEG normal
10
1
9
aEEG mildly abnormal
24
9
15
aEEG severely abnormal
29
24
5
Abbreviation: aEEG, amplitude-integrated electroencephalogram.
Study references
N
PPV (%)
NPV (%)
Sensitivity (%)
Specificity (%)
Shany et al19
39
69
100
100
87
Hellström-Westas et al20
47
86
96
95
89
34
84
92
94
79
56
77
90
93
70
68
86
91
91
86
15
73
91
79
89
160
88
91
93
85
63
81
70
93
41
Eken et al
21
al Naqeeb et al16 Toet et al
22
Shalak et al
23
van Rooij et al Our study
24
Abbreviations: NPV, negative predictive value; PPV, positive predictive value.
activity caught by aEEG in the first few days after birth might mean a poor neurobehavioral prognosis that needs consideration of special intervention. As a result, aEEG pattern of preterm infants in the first days after birth can supply some predictive information for the risk of developing brain damage in the following days and neurobehavioral development in a long period. ter Horst et al have demonstrated that low-voltage patterns within the first 48 hours after admission are predictive of a poor neurological outcome or death.12 Many studies devote their effort on explaining the predictive value of aEEG for neonatal encephalopathy.8,9,19 As shown in ►Table 4, the PPV and NPV of aEEG in our study were 81.1 and 70%, respectively, and the predictive values obtained by different groups are very similar.19–25 A recent study has shown that the combination of early aEEG and clinical examination within the first 12 hours of birth can increase the PPV and specificity compared with either method alone.23 An accurate predictive value can help the physicians to understand the progress of brain damage more easily, and make a quick determination of pharmacological intervention and personalized treatment programs. There are several limitations in this study, such as small sample size and short follow-up time. Besides, the selective bias for hospital from the parents may affect the strength of these conclusions, for example, mothers usually choose the most powerful hospital for such serious diseases. Thus, the patient distribution will be unbalanced among the hospital in Zhengzhou. Therefore, further studies focusing on the correlation between aEEG dynamic monitoring and WMD in large cohort of subjects are recommended, as well as a long-term follow-up time. Meanwhile, further research is in great need
to clarify the accurate relationship between aEEG and WMD, especially the precise predictive value of aEEG for WMD. In conclusion, abnormal aEEG of preterm infants within 72 hours after birth may imply damage in white matter and predict poor neurodevelopmental prognosis, including dyskinesia, dysgnosia, or even deaths. The epileptiform activity patter might indicate a severe neurodevelopmental prognosis. Further study can emphasize on the precise predictive value of aEEG on WMD in a large cohort of subjects with a long-time follow-up.
References 1 Wilson-Costello D, Friedman H, Minich N, Fanaroff AA, Hack M.
2
3
4
5
6
Improved survival rates with increased neurodevelopmental disability for extremely low birth weight infants in the 1990s. Pediatrics 2005;115(4):997–1003 Fellman V, Hellström-Westas L, Norman M, et al; EXPRESS Group. One-year survival of extremely preterm infants after active perinatal care in Sweden. JAMA 2009;301(21):2225–2233 Saliba E, Marret S. Cerebral white matter damage in the preterm infant: pathophysiology and risk factors. Semin Neonatol 2001; 6(2): 121–133 Leviton A, Paneth N. White matter damage in preterm newborns—an epidemiologic perspective. Early Hum Dev 1990; 24(1):1–22 Hellström-Westas L, Rosén I. Electroencephalography and brain damage in preterm infants. Early Hum Dev 2005; 81(3):255–261 Hayakawa M, Okumura A, Hayakawa F, et al. Background electroencephalographic (EEG) activities of very preterm infants born at less than 27 weeks gestation: a study on the degree of continuity. Arch Dis Child Fetal Neonatal Ed 2001;84(3):F163–F167 Neuropediatrics
Vol. 45
No. 5/2014
Downloaded by: Collections and Technical Services Department. Copyrighted material.
Table 4 Predictive values of background patterns in some studies
aEEG Predicts WMD in Preterm Infants
Song et al.
7 Klebermass K, Olischar M, Waldhoer T, Fuiko R, Pollak A, Weninger
8 9
10
11
12
13
14
15 16
17 18
19
20
21
M. Amplitude-integrated EEG pattern predicts further outcome in preterm infants. Pediatr Res 2011;70(1):102–108 Toet MC, Lemmers PM. Brain monitoring in neonates. Early Hum Dev 2009;85(2):77–84 Wikström S, Pupp IH, Rosén I, et al. Early single-channel aEEG/EEG predicts outcome in very preterm infants. Acta Paediatr 2012; 101(7):719–726 Bowen JR, Paradisis M, Shah D. Decreased aEEG continuity and baseline variability in the first 48 hours of life associated with poor short-term outcome in neonates born before 29 weeks gestation. Pediatr Res 2010;67(5):538–544 Toet MC, van Rooij LG, de Vries LS. The use of amplitude integrated electroencephalography for assessing neonatal neurologic injury. Clin Perinatol 2008;35(4):665–678, v ter Horst HJ, van Olffen M, Remmelts HJ, de Vries H, Bos AF. The prognostic value of amplitude integrated EEG in neonatal sepsis and/or meningitis. Acta Paediatr 2010;99(2):194–200 Wikström S. Background aEEG/EEG measures in very preterm infants: Relation to physiology and outcome. Uppsala, Sweden: Acta Universitatis Upsaliensis; 2011 Wikström S, Ley D, Hansen-Pupp I, Rosén I, Hellström-Westas L. Early amplitude-integrated EEG correlates with cord TNF-α and brain injury in very preterm infants. Acta Paediatr 2008;97(7): 915–919 de Vries LS. Neurological assessment of the preterm infant. Acta Paediatr 1996;85(7):765–771 al Naqeeb N, Edwards AD, Cowan FM, Azzopardi D. Assessment of neonatal encephalopathy by amplitude-integrated electroencephalography. Pediatrics 1999;103(6 Pt 1):1263–1271 Tao JD, Mathur AM. Using amplitude-integrated EEG in neonatal intensive care. J Perinatol 2010;30(Suppl):S73–S81 Thornberg E, Thiringer K. Normal pattern of the cerebral function monitor trace in term and preterm neonates. Acta Paediatr Scand 1990;79(1):20–25 Shany E, Goldstein E, Khvatskin S, et al. Predictive value of amplitude-integrated electroencephalography pattern and voltage in asphyxiated term infants. Pediatr Neurol 2006;35(5): 335–342 Hellström-Westas L, Rosén I, Svenningsen NW. Predictive value of early continuous amplitude integrated EEG recordings on outcome after severe birth asphyxia in full term infants. Arch Dis Child Fetal Neonatal Ed 1995;72(1):F34–F38 Eken P, Toet MC, Groenendaal F, de Vries LS. Predictive value of early neuroimaging, pulsed Doppler and neurophysiology in full
Neuropediatrics
Vol. 45
No. 5/2014
22
23
24
25
26
27
28 29
30 31
32
33
34
term infants with hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed 1995;73(2):F75–F80 Toet MC, Hellström-Westas L, Groenendaal F, Eken P, de Vries LS. Amplitude integrated EEG 3 and 6 hours after birth in full term neonates with hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed 1999;81(1):F19–F23 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(2):351–357 van Rooij LG, Toet MC, Osredkar D, van Huffelen AC, Groenendaal F, de Vries LS. Recovery of amplitude integrated electroencephalographic background patterns within 24 hours of perinatal asphyxia. Arch Dis Child Fetal Neonatal Ed 2005;90(3):F245–F251 Chalak LF, Sikes NC, Mason MJ, Kaiser JR. Low-voltage aEEG as predictor of intracranial hemorrhage in preterm infants. Pediatr Neurol 2011;44(5):364–369 Hallberg B, Grossmann K, Bartocci M, Blennow M. The prognostic value of early aEEG in asphyxiated infants undergoing systemic hypothermia treatment. Acta Paediatr 2010;99(4):531–536 Csekő AJ, Bangó M, Lakatos P, Kárdási J, Pusztai L, Szabó M. Accuracy of amplitude-integrated electroencephalography in the prediction of neurodevelopmental outcome in asphyxiated infants receiving hypothermia treatment. Acta Paediatr 2013;102(7):707–711 Viniker DA, Maynard DE, Scott DF. Cerebral function monitor studies in neonates. Clin Electroencephalogr 1984;15(4):185–192 El-Dib M, Chang T, Tsuchida TN, Clancy RR. Amplitude-integrated electroencephalography in neonates. Pediatr Neurol 2009;41(5): 315–326 Scoppa A, Casani A, Cocca F, et al. aEEG in preterm infants. J Matern Fetal Neonatal Med 2012;25(Suppl 4):139–140 Shah DK, Lavery S, Doyle LW, Wong C, McDougall P, Inder TE. Use of 2-channel bedside electroencephalogram monitoring in termborn encephalopathic infants related to cerebral injury defined by magnetic resonance imaging. Pediatrics 2006;118(1):47–55 Lamblin M-D, Walls Esquivel E, André M. The electroencephalogram of the full-term newborn: Review of normal features and hypoxic-ischemic encephalopathy patterns. Neurophysiol Clin 2013;43(5–6):267–287 Scher MS, Steppe DA, Beggarly ME, Salerno DG, Banks DL. Neonatal EEG-sleep disruption mimicking hypoxic-ischemic encephalopathy after intrapartum asphyxia. Sleep Med 2002;3(5):411–415 Shah DK, Zempel J, Barton T, Lukas K, Inder TE. Electrographic seizures in preterm infants during the first week of life are associated with cerebral injury. Pediatr Res 2010;67(1):102–106
Downloaded by: Collections and Technical Services Department. Copyrighted material.
320
