Yu et al. BMC Pediatrics(2024) 24:590
https://doi.org/10.1186/s12887-024-05062-w

BMC Pediatrics

RESEARCH

Open AccessUsing cerebral regional oxygen
saturation and amplitude-integrated
electroencephalography in neonates
on extracorporeal membrane oxygenation:
preliminary experience from a single center
Ling-Shan Yu1, Xiu-Hua Chen1, Si-Jia Zhou1, Yi-Rong Zheng1, Zeng-Chun Wang1† and Qiang Chen1*†
Abstract
Objective This study aims to evaluate the application value in neurological outcome of cerebral regional
oxygen saturation (CrSO2) and amplitude-integrated electroencephalography (aEEG) monitoring during neonatal
extracorporeal membrane oxygenation (ECMO) courses.
Methods We retrospectively analyzed 18 neonates receiving veno-arterial ECMO (V-A ECMO) support at our hospitalfrom July 2021 to December 2022. Continuous monitoring of CrSO2 and brain electrical activity was conducted usingnear-infrared spectroscopy (NIRS) and aEEG throughout the ECMO treatment. We collected and analyzed related
clinical data.
Results Among the 11 survivors, 5 were categorized as the normal group (N group) and 6 as the abnormal group(AN group) based on post-ECMO brain MRI outcomes. The N group exhibited shorter time percentage of significant
CrSO2 reduction (> 25% from baseline or absolute value < 40%), better fractional tissue oxygen extraction (FTOE)
rates, and more stable mean percentage changes in CrSO2 compared to the AN group. Neonates in the N grouppredominantly showed mildly abnormal aEEG readings, with one patient displaying disrupted sleep-wake cycles. Thisparticular patient also had more significant CrSO2 reduction and poorer FTOE compared to others in the N group.
Additionally, the Test of Infant Motor Performance (TIMP) scores indicated hypoevolutism in this patient before
discharge, while others in the N group had normal TIMP scores. In the AN group, 4 exhibited moderate and 2 severeaEEG abnormalities; 5 had hypoevolutism TIMP scores, and 1 with moderate aEEG abnormalities maintained a normal
TIMP score, exhibiting lesser CrSO2 reduction and improved FTOE.

†

Zeng-Chun Wang and Qiang Chen shared the corresponding
authorship.
*Correspondence:
Qiang Chenchenqiang2228@163.com
Full list of author information is available at the end of the article© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0
International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you
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Yu et al. BMC Pediatrics(2024) 24:590

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Conclusion CrSO2 and aEEG monitoring show potential as routine assessments for neurological outcomes during
neonatal ECMO. In our cohort, a tendency was observed where neonates with greater reductions in CrSO2 and more
severe aEEG abnormalities experienced poorer neurological outcomes.
Keywords Neonates, ECMO, Cerebral regional oxygen saturation, Early results

Introduction
Extracorporeal membrane oxygenation (ECMO) is theultimate treatment modality for neonates facing severe,
reversible respiratory or circulatory failure. The ECMO
procedure in neonates entails the ligation and cannulation of right cervical vessels, blood interfacing with artificial membranes, and anticoagulation therapy, all of which
can lead to significant cerebral hemodynamic alterations.
These procedural elements, combined with the potential
for bleeding and embolization, increase the risk of severe
brain injury and adverse neurodevelopmental outcomes[1]. Additionally, the inherent fragility and developmental
immaturity of neonatal vascular networks, along with thepossible impairment of cerebral autoregulation during
ECMO, place these patients at an increased risk for brain
injury [2]. Impaired cerebral autoregulation is associatedwith poor neurodevelopmental outcomes [3]. Cerebral
hemorrhage, the most frequent neurological complication, is linked with the highest mortality. Other serious
neurological complications, including ischemic stroke,
hypoxic-ischemic encephalopathy, and epileptic seizures, can also lead to death [4]. Despite improvements
in ECMO management techniques reducing deaths fromneurological complications, the incidence of near-termand long-term adverse neurological outcomes remains
high, particularly in neonates [4–6]. In neonates who
survive ECMO support, neurological complications suchas periventricular leukomalacia, cerebral palsy, sensorineural hearing loss, and intellectual impairment arecommon. Consequently, monitoring brain function during the ECMO period is crucial to identify and mitigate
these risks effectively. This vigilant approach is essential
for improving neurological outcomes and overall qualityof life for these vulnerable patients.
Cerebral regional oxygen saturation (CrSO2) monitoring, utilizing near-infrared spectroscopy (NIRS), is
instrumental in detecting levels of cerebral oxyhemoglobin (HbO2) and deoxygenated hemoglobin (HbR),
thereby measuring regional blood oxygen saturation [7].
This technique has become a vital tool for monitoring
neonatal tissue hypoxia and cerebral injuries [8]. Studies have shown that lower CrSO2 measurements correlate with poorer neurological outcomes and increased
perioperative mortality. Real-time monitoring of CrSO2
offers early detection of hypoxia, often before it is evident through routine invasive hemodynamic monitoring,enabling prompt intervention to mitigate organ damage[9]. Due to its non-invasive nature, continuous bedsidecapability, absence of ionizing radiation, and compatibility with other monitoring equipment, CrSO2 monitoringis increasingly recommended as a standard procedure
during ECMO support [10]. Alongside CrSO2, the amplitude-integrated electroencephalogram (aEEG) — a simplified, filtered, and compressed EEG trend — is gaining
prominence in neonatal intensive care units (NICU) for
assessing neurodevelopmental outcomes [11]. This dual
monitoring strategy enhances the ability to predict andmanage potential neurological issues in vulnerable neonatal populations.
The utility and empirical support for using CrSO2 andaEEG to assess cerebral hypoxia and neurological outcomes in neonates during ECMO are not fully established. This study was designed to explore the application
value and effectiveness of CrSO2 and aEEG monitoringin evaluating neurological outcomes during neonatal
ECMO treatment periods.

Materials and methods
We obtained written informed consent from the parentsof the patients involved. This retrospective observational
study collected data through our medical record system, focusing on 18 neonates who received venoarterial
ECMO (V-A ECMO) support from July 2021 to December 2022. We excluded seven neonates due to death or
pre-existing central nervous system conditions, including
cerebral hemorrhage, cerebral infarction, and epilepsy,
prior to ECMO support. Ultimately, 11 neonates were
included in the study, all of whom were intubated nasallyand managed with controlled ventilation settings before
ECMO initiation. Our protocol adhered to the ELSO
Neonatal Respiratory Support Guidelines [12]. ECMO
assistance was considered when a patient’s respiratoryor hemodynamic status was unstable and met one of thefollowing criteria: (1) reversible cardiopulmonary failure;(2) oxygenation index > 40 for over 4 h; (3) oxygenationindex > 20 after 24 h of conventional treatment; (4) severe
progressive respiratory failure or associated with circulatory failure, or prolonged use of high-dose cardiovascular
drugs.
Following the removal of ECMO, brain magnetic resonance imaging (MRI) was conducted to detect any radiographic central nervous system abnormalities. Using
the MAGNETOM Prisma 3.0T scanner, the MRIs werecategorized, and a unified team of imaging doctors
interpreted the results. The abnormal findings included
reduced white matter around the posterior horn of theYu et al. BMC Pediatrics(2024) 24:590

bilateral lateral ventricles, widened subarachnoid spaceat the left infratemporal pole, slightly deeper bilateralfrontotemporal sulci, right frontal softening focus withdeeper sulci, enlarged ventricles, and deeper frontotemporal sulci on both sides. Based on the imaging results, 5cases were classified as belonging to the N group (normalgroup) and 6 to the AN group (abnormal group), indicating variations in the severity and presence of neurologicalimpairments.
Throughout the ECMO course, Near-Infrared Spectroscopy (NIRS) was employed to continuously monitor
CrSO2 using the INVOS™5100 C (Kehui Medical Equipment International Trading Co., LTD). Data from thedevice was exported via USB flash drive. The INVOS
Monitoring Analytics TOOL software was used to analyze desaturation events and establish CrSO2 baselines. A
NIRS neonatal sensor was positioned at the median forehead of each patient, with a baseline reading recorded
after a 5-minute stabilization period pre-ECMO. (Fig. 1)
Desaturation was defined as a reduction in CrSO2 greaterthan 25% from baseline or an absolute value of CrSO2
less than 40% during ECMO, following criteria established in previous adult ECMO studies [13]. To minimize
confounders, data from cannulation and de-cannulation
phases were excluded from the analysis. Our approach
was proactive, aiming to maintain CrSO2 at normal baselines. Upon detecting desaturation, our first response
was to check the sensor’s position, patient’s head, andthe arterial and venous cannulas. If hypotension was suspected, cardiac output was optimized, and vasopressors
were administered to maintain a mean perfusion pressure of 40–45 mmHg in normothermia. When meanarterial pressure (MAP) was normal, abnormal systemic
oxygenation was corrected, a better acid-base balanceand partial pressure of carbon dioxide (PaCO2) levels
were obtained by adjusting the ventilation or modifying
the oxygenator. Red blood cell transfusions were considered to maintain hemoglobin levels above 100 g/L.
If these steps didn’t improve CrSO2, deeper anaesthesia

Fig. 1 CrSO2 graphical value of one neonate during the study

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and analgesia, temperature adjustments, and anticonvulsants were considered to decrease cerebral oxygen consumption. (14–15) These events and interventions were
all recorded in the INVOS monitor. Our management of
pH and arterial gases during ECMO aimed for specificranges: PH:7.35–7.45, SvO2:65–80%, SPO2 > 90%, PaO2:
60–80 mmHg, PaCO2: 40–45 mmHg, HCO3-: 22–27
mmol/L, BE: ±3 mmol/L, and Lac: < 1.6mmol/L. Scalp
electrodes and multichannel aEEG were implemented
for continuous EEG activity monitoring throughout the
ECMO treatment.
Our study conducted a detailed statistical analysis,
encompassing various aspects of the neonatal patientsand their ECMO treatment. Data were gathered andanalyzed, including: (1) general patient information likeage, body weight, gender, primary disease, and clinical symptoms; (2) average heart rate (HR), peripheral
blood oxygen saturation (SpO2), MAP, and ECMO support duration; (3) time percentage of CrSO2 reduction
greater than 25% or absolute value less than 40% during
ECMO (to calculate the time percentage of CrSO2 reductions during ECMO, we divided the cumulative time that
CrSO2 was lower than the established cutoffs (greaterthan 25% reduction from baseline or an absolute valueless than 40%) by the total duration of the ECMO course.
This method provided us with a proportion, expressed
as a percentage, indicating the extent of time the patient
spent under these critical CrSO2 thresholds while receiving ECMO support.); [16] (4) the mean percentagechange in CrSO2 (We recorded the CrSO2 value of eachhour during the ECMO support process, calculated thevalue of CrSO2 less than or greater than the baseline ateach time point, the positive value was above the baseline, the negative value was below the baseline, and thenthe sum of each time point was divided by the total monitoring time.); (5) fractional tissular oxygen extraction(FTOE) during ECMO; (6) aEEG monitoring results; and(7) post-ECMO brain MRI findings and Test of Infant
Motor Performance (TIMP) scores before discharge. This
comprehensive dataset aimed to provide a robust foundation for evaluating the efficacy of ECMO support andits impacts on neonatal patients, with a particular focus
on neurological outcomes.
Neonatal EEG activity is classified according to
amplitude and continuity using the aEEG with a widely
accepted five-classification method proposed by Hellström-Westas et al. [17] The classifications are: (1)Continuous Normal Voltage, characterized by lower
boundary amplitude fluctuations between 5 and 10 µV
and upper boundary fluctuations between 10 and 25 µV,
not exceeding 50 µV; (2) Discontinuous Normal Voltage, where background activity is discontinuous, lower
boundary amplitude does not exceed 5 µV, and the upperboundary is greater than 10 µV; (3) Burst Suppression,Yu et al. BMC Pediatrics(2024) 24:590

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featuring discontinuous background activity, lower
boundary amplitude between 0 and 2 µV, burst amplitude exceeding 25 µV, with burst density classified as
BS + if ≥ 100 bursts/h and BS- if < 100 bursts/h; (4) Continuous Low Voltage, with continuous background activity and significantly reduced amplitude, upper boundary
less than 10 µV and lower boundary less than 5 µV; (5)Inactive and Flat Trace, indicating very low voltage
close to electrical silence with amplitude less than 5 µV.
In this system, classification (1) is deemed normal, (2)mildly abnormal, (3) moderately abnormal, and (4) and(5) severely abnormal. This categorization aids in thedetailed assessment of neonatal brain activity and potential neurological conditions.
The TIMP is a scale designed to assess motor and postural control in infants, specifically tailored for those
aged from 34 gestational weeks to 4 months of correctedgestational age. It evaluates the infant’s motor control
and postural coordination, as well as their motor abilities
in relation to functional activities, serving as a predictor
for future motor development. The TIMP encompasses
42 items, with the first 13 being observational and theremaining 29 eliciting specific motor responses. Uponcompletion of the assessment, a total score is compiled,with scores above a certain cutoff considered “normal”
and those below the threshold regarded as indicative of“hypoevolutism”. Professional and trained rehabilitation
doctors typically conduct the TIMP scoring to ensure
accuracy and reliability in determining infants’ motor
developmental status [18].
Statistical analysis

All data were analyzed using IBM SPSS statistical software, version 20.0. Counts and percentages were used todescribe the categorical data. The continuous variables
were expressed as median and inter-quartile range (IQR).

Results
Patient characteristics and vital signs

This study included 11 surviving neonates who received
V-A ECMO support, with primary indications including persistent pulmonary hypertension of the neonate(PPHN), acute respiratory distress syndrome (ARDS),
meconium aspiration syndrome (MAS), postoperative
congenital diaphragmatic hernia (CDH), pertussis withpulmonary artery hypertension (PAH), and PPHN withfetal edema. The clinical characteristics shared among
these cases were progressively worsening respiratory andcirculatory failure. When comparing the normal group(N) and abnormal group (AN) based on the MRI findings, the median age was 2.0 (1.5, 3.0) days for group
N and 5.2 (1.0, 7.5) days for group AN, and the medianweight was 3.7 (3.2, 3.8) kg for group N versus 3.4 (3.0,
3.8) kg for group AN. The median values for MAP, SpO2,and HR during ECMO treatment were 47.0 (45.5, 48)
mmHg vs. 46.5 (42.8, 49.3) mmHg, 95.0 (94.5, 96.0)%
vs. 95.0 (93.8, 96.0)%, and 143.0 (142.5, 145.5) beats/min vs. 145.5 (141.8, 147.3) beats/min in groups N and
AN respectively. Additionally, the median duration of
ECMO support was 86.0 (78.0, 94.5) hours for group N
and 84.3 (78.5, 92.5) hours for group AN. These findings
and comparisons are further detailed in Tables 1 and 2 ofthe study.
CrSO2 changes during ECMO course

In our study, the median baseline CrSO2 prior to ECMO
initiation was 52.2 (52.0, 55.5) for the normal group (N)and 50.7 (51.0, 53.8) for the abnormal group (AN) as
detailed in Table 2. The group N showed a smaller percentage of time with CrSO2 reduction greater than 25%
from baseline or absolute CrSO2 less than 40%, indicating
better oxygenation status than group AN. Furthermore,
FTOE and the mean percentage change in CrSO2 weremore favorable in group N compared to group AN, suggesting more stable and effective oxygenation.

Table 1 Patient’s characteristics
1
2
3
4
5
6
7
8
9
10
11

Age (days)
3
3
2
2
1
2
1
1
24
1
2

GenderMale
Male
FemaleFemaleFemaleMale
Female
Male
Male
Male
Male

Weight (kg)
3.9
3.8
3.7
2.99
3.5
3.15
3
2.8
4.2
3.65
3.6

Primary disease
PPHN, ARDS
PPHN, ARDS
MAS, PPHN
CDH, PPHN
MAS, PPHN
PPHN, ARDS
PPHN, ARDS
PPHN, ARDS
Pertussis, PAH
PPHN, fetal edema
CDH, PPHN,

Clinical symptoms
Respiratory, circulatory failure
Respiratory, circulatory failure
Respiratory, circulatory failure
Respiratory, circulatory failure
Respiratory, circulatory failure
Respiratory, circulatory failure
Respiratory, circulatory failure
Respiratory, circulatory failure
Respiratory, circulatory failure
Respiratory, circulatory failure
Respiratory, circulatory failure

PPHN, persistent pulmonary hypertension of the new-born; ARDS, acute respiratory distress syndrome; MAS, meconium aspiration syndrome; CDH, congenital
diaphragmatic hernia; PAH, pulmonary artery hypertension

Yu et al. BMC Pediatrics(2024) 24:590

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Table 2 MAP, SpO2, HR, and CrSO2, FTOE during ECMO course
The mean value of MAP (mmHg)
The mean value of SpO2(%)
The mean value of HR (beats/min)Duration of ECMO support (h)CrSO2 baseline prior to ECMO
Time percentage of CrSO2 decline > 25% from baseline (%)
Time percentage of CrScO2 < 40%(%)
The mean percentage change in
CrSO2 (%)
FTOE

Group N(n = 5)47.0 (45.5, 48)
95.0 (94.5, 96.0)

Group AN(n = 6)46.5 (42.8, 49.3)
95.0 (93.8, 96.0)

143.0 (142.5,
145.5)
86.0 (78.0, 94.5)
52.0 (49.0, 55.5)
24.6 (17.9, 27.1)

145.5 (141.8,
147.3)
84.0 (78.5, 92.5)
51.0 (47.3, 53.8)
43.3 (40.3, 46.9)

18.8 (8.4, 22.6)

34.8 (22.2, 46.4)

9.0 (7.5, 10.0)

1.0 (0.8, 4.0)

0.36 (0.35, 0.38)

0.43 (0.42, 0.56)

The continuous variables were expressed as median and inter-quartile range(IQR). MAP, mean arterial pressure; SpO2, peripheral blood oxygen saturation;
HR, heart rate; FTOE: fractional tissular oxygen extraction; CrSO2, cerebral
regional oxygen saturation

Notably, within group N, one patient was identified
with a TIMP score indicative of hypoevolutism; thispatient experienced more significant CrSO2 reduction
and worse FTOE compared to others in the same group.
Conversely, in group AN, one patient had a normal TIMP
score and demonstrated lesser CrSO2 reduction and better FTOE relative to peers in that group. The brain MRIof this particular patient revealed slightly deeper sulci but
no other significant changes in brain parenchyma.
aEEG during ECMO course

In the study, neonates in group N with normal brain MRI
results exhibited mildly abnormal aEEG results. Within
this group, one patient lacked a sleep-wake cycle and was
identified with a TIMP score indicative of hypoevolutism

prior to discharge. Conversely, the neonates categorized
in group AN due to abnormal brain MRI results displayed more significant aEEG abnormalities: four had
moderate abnormalities and two severe. The brain MRIof those with moderate aEEG abnormalities typicallyshowed reduced white matter around the bilateral lateral
ventricles’ posterior horns, widened subarachnoid spaceof the left infratemporal pole, and deeper frontotemporal sulci, right frontal softening focus, with one patient
showing a normal TIMP score but slightly deeper sulci
without other parenchymal changes. This patient also
had less CrSO2 reduction and better FTOE comparedto others in AN. The patients with severe aEEG abnormalities and electrical silence had MRI results indicating enlarged ventricles and deeper frontotemporal sulci.
These two patients experienced greater CrSO2 reduction
and worse FTOE compared to their peers in the samegroup and were all scored as hypoevolutism on the TIMP.
(Table 3)
These findings illustrate a correlation between theseverity of EEG abnormalities, structural brain changes,
and functional outcomes, underscoring the importanceof integrated neuro-monitoring in assessing and understanding the complex impacts of ECMO on neonatal
neurological health.

Discussion
We performed a descriptive analysis and found the tendency that the neonates with lower CrSO2 and worseaEEG during ECMO might have the worse TIMP scoreand abnormal MRI results. In this study, group N demonstrated a lower percentage of time with significant CrSO2
reduction and exhibited better FTOE and mean percentage change in CrSO2 compared to group AN. Theseobservations align with those reported by Wong et al.,Table 3 aEEG during ECMO course and TIMP score, brain MRI results after ECMO support
aEEG during ECMO
1
2
3
4
5
6
7
8
9
10
11

Mild abnormality (no sleep
and wake cycle)
Mild abnormality
Mild abnormality
Mild abnormality
Mild abnormality
Moderate abnormality
Moderate abnormality
Severe abnormality, electricalsilence
Severe abnormality, electricalsilence,Moderate abnormality
Moderate abnormality

The TIMP score before brain MRI
discharge
results
Hypoevolutism
NormalNnormalNnormalNnormalNnormalHypoevolutism
Hypoevolutism
Hypoevolutism
Hypoevolutism
Hypoevolutism
NnormalNormalNormalNormalNormalThe white matter around the posterior horn of bilateral lateral ventricles was less.
The subarachnoid space of the left infratemporal pole was widened, and thefrontotemporal sulcus on both sides was slightly deeper.
The ventricles on both sides were larger and the frontotemporal sulcus on bothsides was deeper.
The ventricles of both sides were larger and the frontotemporal sulcus of bothsides was deepened.
Right frontal softening focus
The sulcus was slightly deeper.

MRI, magnetic resonance imaging; aEEG, amplitude-integrated electroencephalography; TIMP, Test of Motor Infant PerformanceYu et al. BMC Pediatrics(2024) 24:590

who utilized NIRS for monitoring during ECMO support[13]. Their study identified brain desaturation in all 20
patients undergoing ECMO. Following interventions tocorrect potential mechanical issues and enhance oxygenand blood delivery (like adjusting head position, ECMO
cannulae and sensor placement, increasing ECMO flow
and oxygen supply, and ensuring adequate arterial pressure and hemoglobin levels), 16 patients showed recovery. However, two patients continued to exhibit bilateralpersistent low CrSO2, subsequently diagnosed with diffuse ischemic brain injury. The remaining two patients
had unilateral persistent low CrSO2, which was later
confirmed as unilateral cerebral infarction through imaging. These findings highlight the criticality of continuous
monitoring and timely intervention in managing cerebral
oxygenation and mitigating potential adverse neurological outcomes during ECMO support.
In the realm of ECMO-supported patient care, prospective studies have linked acute brain injury to the frequency, duration, and intensity of desaturation episodes
as detected by CrSO2 monitoring [19]. A notable increasein acute brain injury rates has been observed correlatingwith decreased CrSO2 levels. Another study confirmed
the utility of CrSO2 monitoring during ECMO in early
detection of potential brain damage [20]. In recent years,
CrSO2 monitoring has become a prevalent method forassessing brain function during ECMO, particularly due
to its ability to provide continuous, non-invasive insights
into cerebral oxygenation trends. However, while it’s
widely used, the evidence and advantages of CrSO2 inevaluating the extent of cerebral hypoxia and predicting neurological outcomes in neonates are not as robust.
Given that cerebral perfusion and oxygenation disorders significantly contribute to neonatal brain injury andincrease the risk of adverse neurodevelopmental outcomes, understanding and monitoring these parameters
are crucial [21]. In our study, we defined desaturation
based on a set reduction in CrSO2 (> 25% from baselineor an absolute value < 40%) during ECMO, aligning withestablished criteria [13]. Additionally, we incorporated
FTOE as an indicator of the balance between oxygen
delivery and consumption, combining it with measurements like SpO2, HR, MAP, and CrSO2 to analyze cerebral metabolic demand [22]. Our findings revealed thatpatients with lesser CrSO2 reduction and better mean
percentage change in CrSO2 typically had improved
FTOE, mirroring the beneficial application of CrSO2 inother neonatal care areas [9]. In our patient cohort, one
individual in group N was noted to have hypoevolutism
according to the TIMP score before discharge, with thispatient also showing greater CrSO2 reduction and worse
FTOE compared to others in the group. Conversely, ingroup AN, one patient had a normal TIMP score before
discharge, coupled with lesser CrSO2 reduction andPage 6 of 8

better FTOE, demonstrating the variable impacts andpotential benefits of meticulous CrSO2 and FTOE monitoring. These nuanced differences underscore the variability of outcomes and indicators within each group,emphasizing the importance of individualized monitoring and assessment in ECMO treatment.
Polito et al. reported that approximately 20% of neonates receiving ECMO support experienced neurological sequelae [23], a finding echoed by Madderom et al.
[24] Additionally, of those children who suffered brain
injury post-ECMO, 36–38% survived until 20 days postdischarge, with 9–26% exhibiting mild motor or cognitive
impairments at longitudinal follow-up [25, 26]. These statistics underline the significant risk of neurological damage and neurodevelopmental delays among neonates andchildren recovering from critical illnesses treated with
ECMO. Such individuals are also more susceptible toworsening of pre-existing medical conditions and development of new medical comorbidities [27]. These factors make the continuous monitoring of brain function
an essential component of neonatal ECMO care, aiming
to promptly identify and mitigate potential neurologicalcomplications.
NIRS, while effective in reaching the grey matter of thebrain, has limitations in penetrating deeper into the brain
parenchyma [8]. This limitation restricts NIRS’s ability tomonitor the entire brain parenchyma comprehensively.
Additionally, NIRS has a lower spatial resolution compared to MRI and a lower temporal resolution than aEEG
[7]. Therefore, utilizing various examination modalities
is critical to objectively evaluate neonatal brain function,encompassing aspects of brain structure, electrophysiology, and oxygenation metabolism to identify potential brain injuries [8]. In our study, we employed a dual
approach by combining aEEG and CrSO2 monitoring toprovide a comprehensive evaluation of brain function
in neonates undergoing ECMO support. Additionally,
post-ECMO support, MRI findings combined with TIMP
scores were utilized as outcome indicators to assess theextent of any brain injury and the developmental prospects of the neonates.
Electroencephalography serves as a fundamental clinical neurophysiology tool, widely recognized for its effectiveness in diagnosing, monitoring, and prognosticatinga variety of brain disorders in critically ill patients [28].
aEEG is particularly noted for its sensitivity in early outcome prediction, especially in term asphyxiated infants[29]. In our study, we observed a correlation where theseverity of a patient’s aEEG abnormalities was directly
associated with more profound CrSO2 reduction, deteriorated FTOE, poorer TIMP scores, and more adverse
findings in brain MRI results. This pattern emphasizes
the interconnectedness of these variables and highlights
the utility of comprehensive monitoring for a holistic

Yu et al. BMC Pediatrics(2024) 24:590

understanding of the neonate’s neurological status during
ECMO support.
MRI is highly favored for neuroimaging in children,
especially after ECMO support, due to its high sensitivity, specificity, and lack of radiation exposure [27]. In
our center, all neonates receiving ECMO support underwent brain MRI before discharge. For the purposes ofthis retrospective study, patients were categorized basedon their post-ECMO support brain MRI results. The
abnormal brain MRI findings in 6 neonates from the AN(abnormal) group post-ECMO indicated various central
nervous system abnormalities, including reduced whitematter, deeper bilateral frontotemporal sulci, enlarged
ventricles, and right frontal softening focus among others. These patients also exhibited more significant CrSO2
reduction, worse mean percentage change in CrSO2, andpoorer FTOE, along with moderate to severe abnormalities in aEEG. The findings of our study align with those of
Wintermark P et al., reinforcing the correlation between
CrSO2, aEEG, and MRI in assessing brain injury in neonates both during and post-ECMO support [30].
The TIMP scores were conducted on neonates posttracheal intubation removal, serving as a prevalentmethod for assessing motor functions in neonates andpreterm infants [31]. In our study, one neonate in group
N displayed mildly abnormal aEEG patterns along with
an absent sleep-wake cycle; this individual’s TIMP score
was recorded as hypoevolutism before discharge, while
the remaining four in the group were scored as normal.
Conversely, in group AN, one patient with moderate
abnormal aEEG had a normal TIMP score, whereas theother five were classified as hypoevolutism. The variability in TIMP scores suggests a degree of subjectivity in theassessment. Despite this, within our limited sample size,a correlation still emerged: greater reductions in CrSO2
and more pronounced abnormalities in aEEG were generally associated with poorer TIMP scores and more
adverse brain MRI findings.
Limitation

This study, while insightful, has several limitations to
consider. Firstly, as a single-center retrospective study
with a small sample size, it lacks the robustness needed
for comprehensive statistical comparative analysis anddefinitive conclusions. Therefore, the results might nothave statistical significance. Secondly, our study only
included neonates receiving V-A ECMO support, limiting the generalizability of our findings to all ECMO-supported children. Thirdly, the CrSO2 monitoring employedin this study has its own limitations. It primarily reflects
the oxygenation status of the brain tissue in the foreheadarea, potentially overlooking variations in other parts ofthe brain. Despite these limitations, our study observeda trend where greater reductions in CrSO2 and more

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pronounced abnormalities in aEEG correlated with worse
neurological outcomes. Although these findings provide
some directional insight for clinical practice, they underscore the necessity for future, larger-scale, multicenterstudies to validate and expand upon these preliminary
conclusions.

Conclusion
CrSO2 and aEEG monitoring show potential as routine
assessments during neonatal ECMO to predict neurological outcomes. In our cohort, a tendency was observed
where neonates with greater reductions in CrSO2 andmore severe aEEG abnormalities experienced poorer
neurological outcomes.
Abbreviations
CrSO2	Cerebral regional Oxygen SaturationaEEG	Amplitude-Integrated Electroencephalography
ECMO	Neonatal Extracorporeal Membrane Oxygenation
NIRS	Near-Infrared Spectroscopy
NICU	Neonatal Intensive Care UnitsFTOE	Fractional Tissue Oxygen Extraction
TIMP	Test of Infant Motor Performance
HbO2	Oxyhemoglobin
HbR	Deoxygenated Hemoglobin
MRI	Brain Magnetic Resonance Imaging
MAP	Mean Arterial Pressure
PaCO2	Partial Pressure of Carbon Dioxide
FTOE	Fractional Tissular Oxygen Extraction
PPHN	Persistent Pulmonary Hypertension of the Neonate
ARDS	Acute Respiratory Distress SyndromeMAS	Meconium Aspiration Syndrome
CDH	Congenital Diaphragmatic Hernia
PAH	Pulmonary Artery Hypertension
Acknowledgements
We highly acknowledge the following researchers’ contributions: Xiu-Xuan
Ruan, Ze-Wei Lin, Wang-Sheng Dai, Li-Wen Wang, and Hong-Lin Wu. Special
thanks to Qi-Liang Zhang for his assistance and guidance in the design andimplementation of this study.
Author contributions
Ling-Shan Yu and Qiang Chen designed the study, performed the statisticalanalysis, participated in the operation, and drafted the manuscript. Xiu-Hua
Chen and Si-Jia Zhou collected the clinical data. Yi-Rong Zheng and ZengChun Wang supervised the study. All authors read and approved the final
manuscript.
Funding
There is no funding.
Data availability
The datasets used and analyzed during the current study are available fromthe corresponding author at the reasonable request.

Declarations
Ethics approval and consent to participate
The ethics committee of Fujian Children’s Hospital granted approval for thisstudy (2022ETKLR12052). We obtained written informed consent from theparents of the patients involved.
Consent for publication
Not applicable.

Yu et al. BMC Pediatrics(2024) 24:590

Competing interests
The authors declare no competing interests.
Author details
1
Department of Cardiac Surgery, Fujian Children’s Hospital (Fujian Branchof Shanghai Children’s Medical Center), College of Clinical Medicine
for Obstetrics & Gynecology and Pediatrics, Fujian Medical University,
Fuzhou, China
Received: 15 August 2023 / Accepted: 5 September 2024

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