Neonatal Electroencephalography

Lena K. Hellström-Westas

Contents Abstract
The electroencephalogram (EEG) records
The Neonatal Electroencephalogram . . . . . . . . . . . . . . 2
Normal EEG Maturation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 electrocortical activity and is a sensitive
Abnormal EEG . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 method for assessing brain function. Neurolog-
Effects of Medications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 ical symptoms may be very vague or entirely
Seizures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 absent in infants requiring neonatal intensive
EEG-Monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 care. The EEG is an important tool for
Seizure Management with aEEG/EEG . . . . . . . . . . . . . . . 8 detecting abnormal brain activity in both term
Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 and preterm infants and can be used for diag-
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 nosing epileptic seizures and following effects
of antiepileptic treatment; the EEG can also
contribute with predictive information on
later neurodevelopmental prognosis.

• The EEG is sensitive for assessing brain

function and for detecting brain
dysfunction.
• The amplitude-integrated EEG trend
(aEEG) can be used for monitoring high
risk infants.
• The aEEG gives prolonged information on
trends in brain activity, while the EEG gives
detailed information and confirms findings
in the aEEG.
• The aEEG and EEG can be used for predic-
tion of outcome, diagnosis of seizures, and
evaluation of effects of antiepileptic
treatment

L.K. Hellström-Westas (*)

Department of Women’s and Children’s Health, University
Hospital, Uppsala University, Uppsala, Sweden
e-mail: lena.westas@kbh.uu.se

# Springer International Publishing AG 2016 1

G. Buonocore et al. (eds.), Neonatology,
DOI 10.1007/978-3-319-18159-2_268-1
2 L.K. Hellström-Westas
The Neonatal Electroencephalogram
The electroencephalogram (EEG) records electro-
cortical activity from the brain’s surface. The EEG
activity is also influenced by subcortical activity;
a dissociation of thalamocortical connection is
associated with the discontinuous burst-
suppression activity. Consequently, the EEG
reflects brain function and can be used for early
detection of both general and focal brain
dysfunction.
The EEG is usually recorded from electrodes
placed over the scalp according to the Interna-
tional 10–20 system which uses the nasion and
the inion as anatomical landmarks on the skull to
identify electrode positions (Jasper 1958). The
inter-electrode distance is usually 10% or 20%
of the total distance between these positions. The
electrode positions are defined by capital letters
followed by a number, for example, F for frontal,
C for central, T for temporal, O for occipital, with
even numbers indicating the right side and odd
numbers the left side (Fig. 1). Additionally, respi-
ration, electrocardiogram, eye movement, and
electromyogram are recorded, which together
with the EEG give supplementary information
such as sleep states, movements, seizures, and
possible artifacts. The EEG changes with the
infant’s maturation. The terms postconceptional
NASION
Fp1 Fp2
F7 F8
F3 Fz F4
A1
T3 C3 Cz C4 T4
P3 Pz P4
T5 T6
O1 O2
INION
Fig. 1 Electroencephalogram electrode positions
according to the International 10–20 system (Jasper
1958). The red circles mark electrode positions that are
age (PCA) and postmenstrual age (PMA) repre-
sent a summary of gestational age and postnatal
age and are used when assessing EEG maturation.
Normal EEG Maturation
Waveforms and background activity in the EEG
can be described according to amplitude, fre-
quency, topographic distribution of activity, and
temporal (time) evolution. The normal EEG back-
ground in very preterm infants is mainly discon-
tinuous, a pattern that is called tracé discontinu
which is characterized by high-amplitude bursts
of activity alternating with periods of low-voltage
activity, interburst intervals (IBI). With increasing
maturation, the duration of the bursts increases,
while their amplitude decreases, and simulta-
neously the IBIs become shorter, resulting in an
increasingly continuous EEG background. The
mean IBI duration is around 18–26 s at
21–24 weeks PCA and decreases to 10–12 s at
25–30 weeks PCA and down to 6–8 s at
34–36 weeks (Fig. 2). The topographic organiza-
tion of the developing EEG occurs in an
occipitalfrontal direction. Interhemispheric syn-
chrony of electrocortical activity changes during
maturation: at extremely low PCA the EEG activ-
ity is usually synchronous, and between 26 and
NASION
Fp1 Fp2
F7 F8
F3 Fz F4
A2 A1 A2
T3 C3 Cz C4 T4
P3 Pz P4
T5 T6
O1 O2
INION
commonly used in newborn infants, on the left side for
neonatal EEG and on the right side long-term monitoring
of aEEG/EEG
Neonatal Electroencephalography 3

Fig. 2 Examples of aEEG trends (duration 6 h) with w stable infant. The aEEG/EEG activity dominated by
corresponding raw EEG (25 s). (a) Single-channel aEEG/ discontinuous activity although short periods of more con-
EEG (P3-P4) from the first day of life in a GA 23+6 tinuous activity can be seen (1). (b) Single-channel aEEG/
4 L.K. Hellström-Westas
30 weeks’ PCA there is increased
desynchronization, which again is followed by
increasing synchronization at PCAs above
30 weeks (André et al. 2010; Mizrahi et al. 2004).
Sleep wake cycling can be identified in the
EEG from around 30 weeks’ PCA, but immature
cycling can be seen already from around
24–25 weeks PCA although specific sleep states
cannot be distinguished. Active sleep, or rapid eye
movement (REM) sleep, can usually not be dis-
tinguished from wakefulness in the EEG without
other measures, that is, direct observation or eval-
uation of eye movements, respiration, and muscu-
lar activity. Quiet sleep, or non-REM, sleep is
characterized by increased discontinuity. The
EEG during quiet sleep in term infants is either
discontinuous (tracé alternant) or contains high
voltage slow activity (HVS) (Fig. 2).
The distribution of the main EEG frequencies,
that is, delta (< 4 Hz), theta (4–8 Hz), alpha
(8–12 Hz), beta (13–20 Hz), also change with
maturation, although there is usually a mix of
frequencies at all PCA. In preterm infants, high
voltage delta activity and, to some extent, theta
activity is predominant, while more theta and
alpha activity can be identified in term infants
(André et al. 2010; Mizrahi et al. 2004). Very
slow EEG activity (<0.5 Hz) has also been dem-
onstrated both in term and preterm infants. Exper-
imental data indicate that this activity may be
essential for the development of brain wiring pro-
cesses (Vanhatalo and Kaila 2006). The EEG sig-
nal is weak (measured in microvolts) and can
easily be disturbed by movements, electrical inter-
ferences in the neonatal intensive care unit
(NICU), and respiration. Especially when the
EEG activity is very depressed, the recording
may pick up the signal from the electrocardiogram
Fig. 2 (continued) EEG (P3-P4) from the first day of life
in a stable infant with GA 27+0 weeks demonstrating
alternating periods with continuous (1) and more discon-
tinuous (2) activity, which may represent crude sleep wake
cycling. (c) Two-day-old full-term infant with a suspected
(ECG), which is measured in millivolt and conse-
quently has a magnitude of 1000 times that of the
EEG. High frequency oscillation ventilation
(HFOV) in the NICU is often performed with
frequencies between 10 and 15 Hz, that is, fre-
quencies that are parts of the normal EEG activity.
Care has to be taken to avoid such interference by
avoiding contact between the electrodes and the
bedding and to evaluate the raw-EEG signal for
this artifact when using amplitude-integrated EEG
(aEEG) monitoring.
During normal EEG maturation, several dis-
tinctive waveforms and patterns are expected to
appear and disappear at certain PCA: these fea-
tures can be used for evaluation of the infant’s
brain maturation, but their functional and anatom-
ical correlates are not known (Vanhatalo and Kaila
2006). Delta brush pattern is characterized by runs
of fast activity (alpha-beta) superimposed on delta
waves; this pattern is typical of the very preterm
EEG. Temporal theta bursts (temporal saw-tooth)
are brief, rhythmic, 4–6 Hz transients that first
appear around 26 weeks’ PCA and reach a max-
imum at 30–32 weeks before they disappear. Tem-
poral sharp waves may appear during the first
weeks of life in infants born at 31–32 weeks’
gestation. However, if abundant, or persisting,
they are associated with brain injury. Frontal
sharp wave transients appear from 34 to
35 weeks’ PCA and disappear around 10 weeks
later (André et al. 2010; Mizrahi et al. 2004).
The accuracy of estimation of PCA from vari-
ous EEG measures is usually 2 weeks. An inter-
esting observation in a few publications is that the
EEG activity in very preterm infants seems to
exhibit a progressive increase during the first
days of life: whether this is due to postnatal adap-
stroke. Continuous aEEG/EEG background with sleep
wake cycling, including (1) tracé alternant sleep, (2) con-
tinuous activity representing wakefulness or rapid eye
movement (REM) sleep, and (3) a brief seizure
Neonatal Electroencephalography
tation or recovery after the delivery is not known
(Victor et al. 2005).
Abnormal EEG
When a hypoxic-ischemic, hemorrhagic, or meta-
bolic insult occurs, for example, perinatal
asphyxia, intracranial hemorrhage, or severe
hypoglycemia, the EEG activity is immediately
affected. The response, a transient depression, is
very similar in humans of all ages and animals.
The magnitude of the EEG depression and the
time to recovery of the EEG background activity
correlates with the severity of the insult. The
electrocortical activity usually recovers after a
time-period that may last from minutes to weeks.
Seizures of varying intensity often develop during
the recovery phase (Watanabe et al. 1999). Sleep-
wake cycling is usually depressed or entirely
absent during the acute stage. Chronic EEG
changes, such as abnormal waveforms or poor
synchronization of activity, may persist as
markers of permanent damage. The consistent
way by which the electrocortical activity behaves
after an insult, and the relation between the sever-
ity of the EEG activity and the brain damage,
makes EEG sensitive for diagnosis of brain dam-
age and for early prediction of outcome.
A severe insult may result in an entirely flat
(inactive, isoelectric) EEG, while milder insults
may only result in subtle slowing of the EEG or
increased discontinuity. Burst-suppression (BS)
and undifferentiated extremely low voltage pat-
terns may also be present after severe insults.
These EEG patterns are associated with increased
risk for adverse outcome in asphyxiated term
infants.
In the preterm infant, milder insults may cause
prolonged IBIs, and more severe insults may also
change the background activity to a BS pattern.
Burst suppression is characterized by bursts of
activity with a flat (inactive) or very
low-amplitude IBIs, as compared to the normal
discontinuous background of the preterm infant in
5
which the IBIs contain more activity. The BS pat-
tern is abnormal at all maturational stages; it is
associated with the presence of brain damage,
administration of sedative medications, and some
rare encephalopathies (mainly nonketotic hyper-
glycinemia and Ohtahara syndrome). In term
infants, a recording with predominant IBI duration
of more than 30 s is highly predictive of death or
poor neurological outcome (Menache et al. 2002).
Chronic stage EEG changes may appear within
a few weeks after an insult and are markers of
persisting brain injury. Chronic stage background
abnormalities can be categorized as being either
dysmature or disorganized. Dysmature EEG pat-
terns are characterized by delayed development
(> 2 weeks) and are associated with cognitive
impairment. Disorganized EEG patterns develop
after severe acute insults and are characterized by
deformity of delta waves and brushes, as well as
presence of abnormal sharp waves; they are
closely associated with white matter damage and
development of cerebral palsy (Okumura et al.
2002). Some waveforms, especially positive
rolandic sharp waves (PRSW), are markers of
white matter damage. PRSW are predictive of
later cerebral palsy when appearing with a fre-
quency of more than two per minute in the neo-
natal EEG (Marret et al. 1992).
Effects of Medications
Administration of antiepileptic or sedative medi-
cations such as benzodiazepines (diazepam, mid-
azolam), phenobarbital, opioids (morphine,
fentanyl), and lidocaine is associated with tran-
sient depression of the EEG background that may
last for minutes to hours. The most common
response to a loading dose of sedative or anticon-
vulsant medication in a term infant with normal
continuous EEG background is a change of the
background activity to a moderately discontinu-
ous pattern. Preterm infants and term infants with
already compromised brain function tend to
respond with more profound discontinuity,
6 L.K. Hellström-Westas
Fig. 3 Two-channel aEEG-recording showing 6 h of
aEEG and 25 s of EEG in a full-term asphyxiated infant
treated with hypothermia. The aEEG/EEG background
was continuous when the infant received diazepam due to
a suspected right-sided electroclinical seizure (seen as
rhythmic activity in F4-P4 and P3-P4). After diazepam,
including burst-suppression pattern. The EEG
background usually recovers within 2–2.5 h after
a single dose of sedative medications in term
infants, but in preterm infants the EEG depression
may last longer (Norman et al. 2013; Shany et al.
2008) (Fig. 3). Repeated doses and continuous
infusion of such medications may, of course, be
associated with prolonged and more marked dis-
continuity. In several studies, it has been demon-
strated that surfactant treatment is associated with a
profound aEEG depression that occurs immedi-
ately after administration and has a duration of up
to 10 min in some infants, the reason for this
response is not known (Hellström-Westas et al.
1992).
Seizures
The electrographic appearance of neonatal sei-
zures can be very variable as regards waveform
morphology, frequency, localization, and
the aEEG trend was moderately depressed for 6 h before
recovery (not shown). The traces are from top to bottom:
aEEG: left side (F3-P3), aEEG: right side (F4-P4), EEG:
left side (F3-P3), EEG: right side ( F4-P4), EEG: cross-
cerebral frontal (F3-F4), EEG: cross-cerebral parietal
(P3-P4)
temporal evolution. A seizure pattern in the EEG
is often defined as “a sudden, repetitive, evolving
and stereotyped ictal pattern with a clear begin-
ning middle and ending and a minimum duration
of 10 seconds” (Shellhaas and Clancy 2007).
However, also ictal patterns with shorter duration
than 10 s, and more prolonged epileptiform activ-
ity, for example, periodic lateralized epileptiform
discharges (PLED), are associated with adverse
outcomes (Oliveira et al. 2000).
Status epilepticus is usually defined as contin-
uously ongoing epileptic activity or repetitive sei-
zures with a duration of more than 30 min.
Seizures are most frequently seen in temporal
and central areas and are less commonly detected
in frontal and occipital EEG leads (Shellhaas and
Clancy 2007; Patrizi et al. 2003). Term infants
tend to have a focal onset of seizures, while sei-
zures in a preterm more often are regional (Patrizi
et al. 2003). Clinical seizure identification can be
difficult, since ill newborn infants may have
seizure-like movements without corresponding
Neonatal Electroencephalography
seizure activity in the EEG. However, several
studies have demonstrated that a majority of neo-
natal seizures actually are entirely subclinical and
these seizures can consequently only be diag-
nosed with EEG.
In babies with electroclinical seizures (clinical
and EEG seizures), administration of antiepileptic
drugs is associated with a phenomenon called
electroclinical dissociation, that is, the clinical
seizures stop while subclinical seizures in the
EEG persist or even increase in numbers (Boylan
et al. 2002).
EEG-Monitoring
Video-EEG monitoring is the gold standard of
EEG-monitoring. However, multiple channel
EEG and video is not available in all NICUs,
and it is often too complicated for the neonatal
staff to interpret the EEG bedside on a 24 h/7 day
basis unless continuous service is provided from
an EEG department. This limitation has, so far,
confined the use of video-EEG to complicated
cases and research studies. In contrast, continuous
EEG-monitoring with limited numbers of chan-
nels, usually one to three (cross-cerebral and
fronto-central or fronto-parietal leads), and
including compressed EEG trends such as the
amplitude integrated EEG (aEEG), is increasingly
used in many NICUs. These monitors are easy to
apply and to interpret by the neonatal staff and can
be used 24/7. The first analogue aEEG monitor
was created in the 1960s by Prior and Maynard
and was called Cerebral Function Monitor (CFM)
(Maynard et al. 1969). Modern digital monitors
display and store the raw EEG, which is also
necessary to assess – at least intermittently – for
correct evaluation of the activity in the aEEG/
EEG and for excluding potential artifacts.
The aEEG trend is derived from the raw EEG;
first the EEG signal is passed through an asym-
metric filter which strongly attenuates low
(<2 Hz) and high (>15 Hz) EEG frequencies,
then the signal undergoes rectification, semi-
logarithmic display (to give better resolution
within very low voltage activity), and time-
compression. The resulting aEEG trend gives a
7
good overview of changes in minimum and max-
imum electrocortical activity over hours and days
(Fig. 2). Maturational aEEG changes parallels the
EEG development, which is expected since it is
derived from the EEG. A main developmental
feature in the aEEG trend is the progressive rise
of the lower border (during the more discontinu-
ous quiet sleep) reflecting the increasing EEG
continuity with increasing gestational age
(Zhang et al. 2011a).
The usefulness of the aEEG has been demon-
strated in a large number of studies in both term
and preterm infants. Several studies have shown
that the findings in aEEG recorded within the first
3–6 h after birth asphyxia are highly predictive of
neurodevelopmental outcome (Spitzmiller et al.
2007). Abnormal background patterns (BS,
extremely low voltage, flat) are predictive of
adverse outcome, while normal continuous or
slightly discontinuous patterns are associated
with normal outcome. Sleep wake cycling
appearing before 36 postnatal hours is associated
with better outcome in infants with moderate
hypoxic-ischemic encephalopathy (HIE). These
studies were all performed in asphyxiated infants
who did not receive treatment with therapeutic
hypothermia. However, postasphyctic interven-
tion with moderate hypothermia is associated
with an altered predictive value of the aEEG/
EEG (Thoresen et al. 2010). This is expected,
since hypothermia is an intervention that aims to
change and improve outcome. In hypothermia-
treated infants, an early normalization of the
aEEG/ EEG is associated with good outcome,
while a delayed recovery of an abnormal aEEG/
EEG background until 36–48 h may still be asso-
ciated with a healthy recovery. It is recommended
to monitor brain function during the whole hypo-
thermia treatment since seizures may appear dur-
ing the rewarming. A full EEG should always be
recorded in these infants.
Also in late preterm infants the aEEG/EEG is
predictive of outcome after perinatal asphyxia
(Jiang et al. 2015). Several studies have also
shown that the early electrocortical background
activity is predictive of outcome in very preterm
infants, including infants with intraventricular
hemorrhages (IVH) and white matter damage
8 L.K. Hellström-Westas
(West et al. 2011; Wikström et al. 2012; Song et al.
2015; Iyer et al. 2015). The highest number of
bursts for a specified time and the lowest
interburst intervals, that is, the best electrocortical
activity, are sensitive measures when the electro-
cortical background is discontinuous. Seizures,
mainly subclinical, may also be prevalent in
infants developing both IVH and periventricular
leukomalacia (PVL). As in more mature infants,
presence of sleep-wake cycling during the first
week of life is usually an indicator of good recov-
ery. However, also extra-cranial factors, such as
cardiac output and blood pressure, and carbon
dioxide levels seem to affect the aEEG/EEG back-
ground in preterm infants.
Seizure Management with aEEG/EEG
Continuous aEEG/EEG-monitoring can be very
useful for early detection of seizures in high-risk
infants. However, the reduced number of EEG
electrodes will record fewer seizures than a full
EEG. Nevertheless, it has been demonstrated that
a single-channel EEG from bilateral central leads,
or a two-channel aEEG/EEG, can record around
75–85% of all seizures in a full EEG (Shellhaas
and Clancy 2007; Zhang et al. 2011b). A reason
for this is that at least 60–70% of neonatal seizures
appear in the central, temporal, and parietal areas
(Patrizi et al. 2003). A high detection rate of
seizures in the aEEG/EEG requires that the full
raw EEG is inspected. If just the aEEG trend is
inspected, only 20–40% of seizures in the EEG
will be detected (Shellhaas et al. 2007). Seizure
identification in the aEEG trend requires the
electrographic features of the seizure to be clearly
distinguishable from the overall background
activity since this will produce a transient change
(often a rise, rarely a brief decrease) in the aEEG
pattern. Repeated seizures and status epilepticus
will result in a pattern similar to a saw-tooth, while
ongoing epileptic seizure activity may be difficult
to distinguish since there is no major change in the
aEEG trend (Figs. 1c and 4). Brief seizures
(< 30 s) may be very difficult to identify in the
compressed aEEG trend, and for this reason it is
also important to review the raw-EEG for seizure
activity. Some of the newer aEEG/EEG monitors
have seizure alerts which can be useful for identi-
fication of brief seizures, although no seizure
alarms have a 100% sensitivity.
Conclusions
The EEG and the aEEG/EEG gives clinically
important information on brain function and can
be used for diagnosing seizures and for evaluation
of brain function through assessment of electro-
cortical background abnormalities. The back-
ground activity shortly after an insult is highly
predictive of neurological injury and outcome.
Metabolic diseases are frequently associated
with background abnormalities and seizures
(Olischar et al. 2012). For continuous monitoring
in the NICU, video-EEG is the gold standard, but
this method is not available for daily use in many
hospitals. Other EEG trends such as IBI or
frequency-based trends may also prove to be of
value for evaluation of brain function. When
aEEG/EEG is recorded with a reduced number
of electrodes, it is necessary to perform repeated
EEGs and perform the monitoring in close collab-
oration with clinical neurophysiologists or
neurologists.
Neonatal Electroencephalography
Fig. 4 Subclinical status epileptics in two full-term
infants treated with moderate hypothermia for perinatal
asphyxia. (a) This figure shows 6 h of aEEG and 25 s of
EEG and a clearly visible saw-tooth pattern indicating
repeated seizures. The seizure pattern disappears after
administration of effective antiepileptic treatment, chang-
ing the background pattern to discontinuous. The seizure
displayed in the EEG started 2 min earlier on the left side
(F3-P3), not shown in the EEG but can be seen in the aEEG
trace. The seizure activity in the EEG is right-sided and can
9
also be seen in frontal (F3-F4) and parietal (P3-P4) leads.
(b) A single-channel recording with aEEG duration 4 h,
and 38 s of EEG below. The seizures are continuously
on-going during the whole aEEG recording, and therefore,
there is no saw-tooth pattern in the aEEG. Inspection of the
raw EEG should identify the seizures, and a seizure detec-
tion alarm would probably also detect the seizures. The
aEEG background looks continuous without any variabil-
ity, but due to the seizures the background activity cannot
be assessed
10
References
André M, Lamblin MD, d’Allest AM et al (2010) Electro-
encephalography in premature and full-term infants.
Developmental features and glossary. Neurophysiol
Clin 40:59–124
Boylan GB, Rennie JM, Pressler RM, Wilson G,
Morton M, Binnie CD (2002) Phenobarbitone, neona-
tal seizures, and video-EEG. Arch Dis Child Fetal
Neonatal Ed 86:F165–F170
Hellström-Westas L, Bell AH, Skov L, Greisen G,
Svenningsen NW (1992) Cerebroelectrical depression
following surfactant treatment in preterm neonates.
Pediatrics 89:643–647
Iyer KK, Roberts JA, Hellström-Westas L et al (2015)
Cortical burst dynamics predict clinical outcome early
in extremely preterm infants. Brain 138:2206–2218
Jasper HH (1958) The ten-twenty electrode system of the
International Federation. Electroencephalogr Clin
Neurophysiol 10:371–373
Jiang CM, Yang YH, Chen LQ et al (2015) Early
amplitude-integrated EEG monitoring 6 h after birth
predicts long-term neurodevelopment of asphyxiated
late preterm infants. Eur J Pediatr 174:1043–1052
Marret S, Parain D, Jeannot E et al (1992) Positive rolandic
sharp waves in the EEG of the premature newborn: a
five year prospective study. Arch Dis Child
67:948–951
Maynard D, Prior PF, Scott DF (1969) Device for contin-
uous monitoring of cerebral activity in resuscitated
patients. Br Med J 29:545–546
Menache CC, Bourgeois BF, Volpe JJ (2002) Prognostic
value of neonatal discontinuous EEG. Pediatr Neurol
27:93–101
Mizrahi EM, Hrachovy RA, Kellaway P (2004) Atlas of
neonatal encephalography, 3rd edn. Lippincott Wil-
liams & Wilkins, Philadelphia
Norman E, Wikström S, Rosén I, Fellman V, Hellström-
Westas L (2013) Premedication for intubation with
morphine causes prolonged depression of electro-
cortical background activity in preterm infants. Pediatr
Res 73:87–94
Okumura A, Hayakawa F, Kato T et al (2002) Develop-
mental outcome and types of chronic-stage EEG abnor-
malities in preterm infants. Dev Med Child Neurol
44:729–734
Olischar M, Shany E, Aygün C et al (2012) Amplitude-
integrated electroencephalography in newborns with
inborn errors of metabolism. Neoplasma 102:203–211
Oliveira AJ, Nunes ML, Haertel LM, Reis FM, da Costa JC
(2000) Duration of rhythmic EEG patterns in neonates:
L.K. Hellström-Westas
new evidence for clinical and prognostic significance of
brief rhythmic discharges. Clin Neurophysiol
111:1646–1653
Patrizi S, Holmes GL, Orzalesi M, Allemand F (2003)
Neonatal seizures: characteristics of EEG ictal activity
in preterm and fullterm infants. Brain Dev 25:427–437
Shany E, Benzaquen O, Friger M et al (2008) Influence of
antiepileptic drugs on amplitude-integrated electroen-
cephalography. Pediatr Neurol 39:387–391
Shellhaas RA, Clancy RR (2007) Characterization of neo-
natal seizures by conventional EEG and single-channel
EEG. Clin Neurophysiol 118:2156–2161
Shellhaas RA, Soaita AI, Clancy RR (2007) Sensitivity of
amplitude-integrated electroencephalography for neo-
natal seizure detection. Pediatrics 120:770–777
Song J, Xu F, Wang L et al (2015) Early amplitude-
integrated electroencephalography predicts brain injury
and neurological outcome in very preterm infants. Sci
Rep 5:13810
Spitzmiller RE, Phillips T, Meinzen-Derr J, Hoath SB
(2007) Amplitude- integrated EEG is useful in pre-
dicting neurodevelopmental outcome in full-term
infants with hypoxic-ischemic encephalopathy: a
meta-analysis. J Child Neurol 22:1069–1078
Thoresen M, Hellström-Westas L, Liu X, de Vries LS
(2010) Effect of hypothermia on amplitude-integrated
electroencephalogram in infants with asphyxia. Pediat-
rics 126:e131–e139
Vanhatalo S, Kaila K (2006) Development of neonatal
EEG activity: from phenomenology to physiology.
Semin Fetal Neonatal Med 11:471–478
Victor S, Appleton RE, Beirne M et al (2005) Spectral
analysis of electroencephalography in premature new-
born infants: normal ranges. Pediatr Res 57:336–341
Watanabe K, Hayakawa F, Okumura A (1999) Neonatal
EEG: a powerful tool in the assessment of brain dam-
age in preterm infants. Brain Dev 21:361–372
West CR, Harding JE, Williams CE, Nolan M, Battin MR
(2011) Cot-side electroencephalography for outcome
prediction in preterm infants: observational study.
Arch Dis Child Fetal Neonatal Ed 96:F108–F113
Wikström S, Pupp IH, Rosén I et al (2012) Early single-
channel aEEG/EEG predicts outcome in very preterm
infants. Acta Paediatr 101:719–726
Zhang D, Liu Y, Hou X et al (2011a) Reference values for
amplitude-integrated EEGs in infants from preterm to
3.5 months of age. Pediatrics 127:e1280–e1287
Zhang L, Zhou YX, Chang LW, Luo XP (2011b) Diagnos-
tic value of amplitude-integrated electroencephalogram
in neonatal seizures. Neurosci Bull 27:251–257