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Continuous electroencephalogram (cEEG) ndings
and neurodevelopmental outcomes in neonates
with congenital heart disease (CHD) at 12-24
months of age
Swetha Padiyar ( swethapadiyar1@gmail.com )
Cleveland Clinic Children's Hospital
Neil Friedman
Barrow Neurological Institute at Phoenix Children's Hospital, Phoenix, AZ https://orcid.org/0000-0002-
7349-7981
Elia Pestana-Knight
Cleveland Clinic
Linda Franic
Cleveland Clinic
Sarah Worley
Cleveland Clinic https://orcid.org/0000-0002-3630-4175
Hany Aly
Cleveland Clinic Children's Hospital https://orcid.org/0000-0001-7395-6394
Article
Keywords:
Posted Date: April 7th, 2023
DOI: https://doi.org/10.21203/rs.3.rs-2734445/v1
License: This work is licensed under a Creative Commons Attribution 4.0 International License.
Read Full License
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Abstract
Objective
This study aims to assess the role of continuous EEG (cEEG) background patterns and duration of cross-
clamp time and cardiopulmonary bypass (CPB) to predict abnormal neurodevelopmental outcomes at
12–24 months on Bayley Scales of Infant and Toddler Development (BSID-III).
Study design: This retrospective cohort study included infants with CHD and cEEG monitoring, who
underwent surgery by 44 weeks gestational age.
Results: 34 patients were included, who were operated at median age − 7 days. Longer duration of cross-
camp time was associated with poor language composite scores (LCS) (p value = 0.036). A signicant
association existed between severity of encephalopathy in 24-hour post-operative period and poor LCS (p
value = 0.026).
Conclusion: Majority of neonates with CHD have below average cognitive, language and motor
composite scores on BSID-III. Longer duration of cross-clamp time and severity of encephalopathy during
24-hour post-operative EEG monitoring are associated with poor LCS.
Introduction
Congenital heart disease (CHD) encompasses both structural and non-structural anomalies present at
birth.1,2 Congenital heart defects or structural malformations of the heart are the most common type of
birth defects in the US with an incidence of 4–50/1000 live births reported by various studies.3 Neonates
with CHD have an increased risk of brain injury. The etiology of brain injury in neonates who undergo
corrective surgery for CHD is multifactorial.4 Hypothesized etiologies include disturbances in brain
metabolic function, brain injury, and abnormal brain development in addition to genetic predisposition.5
Neurodevelopmental disability after congenital cardiac surgery is common and is the most consequential
sequelae of congenital heart disease (CHD).6,7 Recent literature shows higher risk of neurodevelopmental
impairment such as diculties with language, attention, academic achievement, ne and gross motor
skills and psychological factors in this population. 8–11 Prospective studies in infants with CHD who had
undergone cardiopulmonary bypass (CPB) surgery reported cognitive outcomes within the low normal
range with motor outcomes > 1 standard deviation below population means.8,12 Mortality rate and
survival outcomes in neonates with CHD undergoing surgical repair have improved over time, with
advances in medical therapies, surgical techniques and critical care management. It is estimated that
more than 90% of these children survive into adulthood.13 14 Given the increased survival rate, focus has
now shifted from preventing mortality to preventing adverse neurodevelopmental outcomes. Methods to
identify brain injury and predict neurodevelopmental outcomes using non-invasive neuro-diagnostic tests
such as continuous electroencephalography (cEEG) could improve prognostication and long-term
monitoring in these children. The American Clinical Neurophysiology Society (ACNS) guidelines
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recommends long term EEG monitoring in neonates and infants with CHD that require early surgery.15 A
previous study showed that only 55% of infants had normal pre-operative EEG. 16 Clinical seizures during
post-operative period have been described in 5–20% of neonates whereas EEG only seizures are more
common occurring in 5–26% neonates.17–23 A strong predictive value of adverse neurological and
developmental outcomes at 1 year of age was found in neonates who had evidence of seizure activity
within rst 48 hours in the post-operative period.24 Also, increased mortality was signicantly associated
with occurrence of post-operative seizures and delay in recovery of the aEEG background pattern beyond
48 hours.25 The value of cEEG monitoring to assess abnormal cerebral activity in the pre and post-
operative period in larger groups of neonates with CHD undergoing palliative or corrective cardiac surgery
has not been previously reported. The aim of this retrospective cohort study was to assess the role of
cEEG background patterns, presence of sleep wake cycles and seizure activity in the pre-operative and
post-operative period to predict abnormal neurodevelopmental outcomes at 12–24 months in neonates
with congenital heart disease requiring cardiac surgery. We also investigated if there was an association
between cross clamp time, arrest time and CPB time with cognitive, language and motor scores on Bayley
Scales of Infant and Toddler Development (BSID – III) at 12–24 months. The secondary aim was to
evaluate intra-operative factors such as cross clamp time, arrest time and CPB time and its correlation
with cEEG ndings after cardiac surgery. We hypothesized that infants with CHD have abnormal pre-
operative and post- operative cEEG ndings and that these abnormalities were associated with poor
outcomes in BSID- III scores at 12–24 months of age.
Methods
Study population:
This retrospective cohort study was performed at the neonatal and pediatric intensive care units (NICU
and PICU) of Cleveland Clinic Children’s Hospital, Cleveland, Ohio, USA. From the medical records
database, all infants that had been admitted with a diagnosis of CHD between January 2010 to
December 2018 and had been monitored with cEEG were identied. In our hospital, cEEG is a routine
procedure in all critically ill infants with CHD prior to and after cardiac surgery. The surgical management
of CHD did not change during this period. Infants with any type of CHD who underwent cardiac surgery
using CPB from birth until 44 weeks gestational age (GA) were included in the study. Neonates with
gestational age less than 36 weeks, conrmed genetic disorders, multiple congenital anomalies or known
underlying neurological abnormalities were excluded from the study. Infants that were transferred to
another facility prior to critical care service discontinuation and infants who underwent cardiac
transplantation within 30 months of cardiac surgery were also excluded. The study was approved by the
Institutional Review Board (IRB) and Pediatric Institute Research Committee at Cleveland Clinic
Foundation.
Continuous EEG (cEEG):
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A 19-channel continuous cEEG recording was performed prior to and for at least 24 hours after cardiac
surgery. Post-operative cEEG was started after the patient was transferred to the ICU and hemodynamic
stability was achieved. Only infants with pre-operative and post-operative cEEG recordings were included
in this study. Twenty electrodes were placed according to the international 10–20 montage system
(modied for neonates) with collodion adhesive. 9 The cEEG service includes acquisition and review
software, network infrastructure, trained and licensed EEG technologists and physicians. The Cleveland
Clinic EEG laboratory is accredited by ABRET. cEEG was performed using the Nihon-Koden digital video
EEG system with a portable EEG acquisition machine networked to the main server allowing EEG review
at the bedside and also, remotely in the central monitoring unit.
cEEG variables such as background patterns, inter-burst interval (IBI) – amplitude and duration,
symmetry, synchrony, presence of sleep wake cycles, grapho-elements and seizure activity were
assessed. The cEEGs were classied as normal or abnormal based on background patterns. Normal EEG
background was dened as normal continuity and discontinuity (IBI < 4 seconds in quiet sleep), IBI
Amplitude 25–50 µV in awake or active sleep, symmetry and synchrony, spontaneous cycling among
wake, active and quiet sleep and normal grapho-elements. Furthermore, severity of encephalopathy was
graded as mild, mild-moderate, moderate, moderate-severe, severe encephalopathy according to
classication of neonatal EEGs by Shellhaas et al based on EEG background features including presence
or lack of continuity or discontinuity, synchrony, symmetry, IBI amplitude and duration and grapho-
elements seen during most part of the EEG recording. 15,26 Sleep wake cycle was graded as normal or
absent. Epileptic activity was classied as single seizure, multiple seizures or status epilepticus. Ictal
discharges were characterized for timing, multifocality, lateralization and anti-seizure medication.
Immediate post-operative EEG was obtained as bedside cEEG monitoring for initial 60 minutes post-
surgery. All neonatal EEGS were interpreted by the pediatric epileptologist team for clinical purposes. For
the study, cEEG recordings were assessed independently by two investigators, one a neonatologist with
experience in cEEG interpretation and second, a senior EEG technician. If any discrepancies in ndings
were noted, nal decisions were made by a pediatric epileptologist. cEEG ndings were described for the
entire length of available recording for each neonate.
Bayley Scales of Infant and Toddler Development – 3rd edition (BSID-III):
The Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III; Bayley, 1993, 2006) is an
individually administered instrument designed to assess the developmental functioning of infants,
toddlers, and young children aged between 1 and 42 months. The Bayley-III provides coverage of the
following ve domains: cognitive, language, motor, adaptive, and social-emotional development. For this
study, we used the three main domains – cognitive scale, language scale (includes receptive and
expressive communication) and motor scale (includes gross and ne motor skills). A mean composite
score of 100 was considered within normal limit, with a standard deviation of 15. A score between 70–85
was considered as mild delay, scores between 55–70 as moderate delay and scores below 55 was
classied as profound delay.
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Clinical Parameters:
Baseline characteristics that were recorded included demographics, birth history (gestational age, birth
weight, Apgar scores, cord pH, mode of delivery), type of CHD and details pertaining to the surgery
including age at surgery, pre-operative and discharge oxygen saturation, The Society of Thoracic
Surgeons-European Association for Cardio-Thoracic Surgery (STAT) score, type of surgical repair, time to
rst chest closure, days till rst extubation, extra-corporeal support days, CPB time, cross clamp time,
regional cerebral perfusion time, cardiac arrest requiring cardiopulmonary resuscitation, acute kidney
injury, intensive care length of stay, total length of stay, use of steroids and sedatives started in 24–48
hours post operatively were also noted. Neonates were classied as Class 1 (Two ventricles with no aortic
arch obstruction), Class 2 (Two ventricles with aortic arch obstruction), Class 3 (One ventricle without
arch obstruction), and Class 4 (One ventricle with arch obstruction) based on the American Heart
Association (AHA) anatomic classication of CHD.
Data Collection:
Data were collected and managed using Research Electronic Data Capture (REDCap), a web based
electronic application through Cleveland Clinic Children’s Hospital.
Statistical Analysis:
All statistical analyses were performed using SAS 9.4 software (SAS Institute, Cary, NC). All analyses
were performed on a complete-case basis and all tests were two-tailed and performed at a signicance
level of 0.05. Data were described using medians and ranges for continuous variables and counts and
percentages for categorical variables. Associations of cEEG ndings were assessed using non-parametric
Kruskal-Wallis tests for categorical variables and Spearman rank correlations for continuous and ordinal
ndings. P- values of < 0.05 were considered to indicate statistical signicance.
Results
A total of 98 patients with CHD who underwent surgical correction with CPB were identied. Of these 98
patients, 87 patients underwent surgery by chronological age of 44 weeks. 21 patients were excluded
from the study. The reasons for not undergoing cEEG monitoring included patients transferred from
outside facilities for surgical correction and critical clinical condition in the immediate post-operative
period requiring repeat surgical intervention. 32 infants had no EEG recordings or BSID follow up. The
nal cohort consisted of 34 infants as shown in Fig. 1.
Patient demographic characteristics and neurological assessments are shown in Table 1. Of the 34
patients included in the study, 21 (62%) were males and 32 (94%) belonged to non-Hispanic ethnic group.
The median gestational age was 39 weeks (IQR 36–42). Surgery in these infants took place at median
age of 7 days (IQR 0–44), with median length of ICU stay of 13 days (IQR 2.0–69) and total length of
stay 24 days (IQR 8.0–218). 1 out of 34 patients died in the post-operative period, with an overall
Page 6/20
mortality rate of 2.9%. All 34 neonates had neurological abnormalities during long term follow-up. Most
common neurological abnormality observed was developmental delay (76%) and microcephaly (35%).
Only 3 neonates had pre-operative MRI done, all of which were abnormal showing a stroke in 2 out of 3
neonates. 34 neonates had pre- and 18 neonates had post-operative head US obtained showing
abnormal results in 33% of neonates after surgery.
The cardiac defects were Class 1 in 14 neonates (41%), Class 2 in 6 neonates (18%), Class 3 in 6
neonates (18%) and Class 4 in 8 neonates (24%) as shown in Table 2. The median duration of CPB was
117 minutes (IQR 0-166) and cross clamp time was 50 minutes (IQR 0–81). Two neonates (5.9%) were
placed on ECMO with 20% requiring ECMO for 2 days and 20% neonates for 3 days.
Table 1. Descriptive statistics, neurological status and classication of cardiac defects and surgical
procedures for infants with congenital heart disease (N=34)
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Page 8/20
Table 2. Descriptive statistics for neurocognitive outcomes at 12-24 months
Page 9/20
Total
(N=34)
Factor N Statistics
Age at BSIDa (months), median (min, max) 34 17 (12, 24)
BSID Cognitive Scaled, median (min, max) 34 8.0 (1.0, 15)
BSID Cognitive Composite, median (min, max) 34 90 (55, 125)
BSID Cognitive Percentile, median (min, max) 34 25 (0.10, 95)
BSID Cognitive Category, n (%) 34
Extremely Low 4 (12)
Borderline 3 (8.8)
Low Average 7 (21)
Average 13 (38)
High Average 4 (12)
Superior 3 (8.8)
BSID Language Scaled, median (min, max) 33 14 (2.0, 32)
BSID Language Composite, median (min, max) 33 83 (47, 135)
BSID Language Percentile, median (min, max) 33 13 (0.10, 99)
BSID Language Category, n (%) 33
Extremely Low 8 (24)
Borderline 7 (21)
Low Average 7 (21)
Average 9 (27)
High Average 1 (3.0)
Very Superior 1 (3.0)
BSID Motor Scaled, median (min, max) 34 13 (2.0, 28)
BSID Motor Composite, median (min, max) 34 78 (46, 124)
BSID Motor Percentile, median (min, max) 34 6.5 (0.10, 95)
BSID Motor Category, n (%) 34
Extremely Low 9 (26)
Page 10/20
Total
(N=34)
Factor N Statistics
Borderline 9 (26)
Low Average 5 (15)
Average 9 (26)
High Average 1 (2.9)
Superior 1 (2.9)
StatisticspresentedasMedian(min,max),N(column%).
aBSID Bayley Scale of Infant Development
Table 3. Predictors of cognitive, language and motor composite score (CCS) at 12-24 months
Page 11/20
Cognitive composite
score Language composite
score Motor composite score
Factor N Statistics P
value N Statistics P
value N Statistics P
value
Pre-op EEG
Interburst Interval
- Amplitude
32 0.09
(-0.27,
0.43)
0.62 32 -0.06
(-0.40,
0.30)
0.76 32 0.04
(-0.32,
0.38)
0.84
Pre-op EEG
Interburst Interval
- Duration
32 -0.08
(-0.42,
0.28)
0.67 32 -0.04
(-0.39,
0.32)
0.85 32 -0.13
(-0.46,
0.23)
0.48
Post-op EEG
Continuous
. No
. Yes
32 0.26 32 0.066 0.45
17 95 [80,
110] 17 89 [77,
103] 17 82 [67,
97]
15 90 [75,
95] 15 77 [62,
94] 15 73 [70,
91]
Post-op EEG
Discontinuous
. No
. Yes
32 0.21 32 0.065 0.54
14 90 [75,
95] 14 76 [62,
94] 14 76 [70,
91]
18 95 [80,
110] 18 88 [77,
103] 18 82 [67,
97]
Post-op EEG
Synchronous
. No
. Yes
32 0.37 0.27 0.60
11 90 [80,
95]
11 83 [59,
94]
11 73 [64,
97]
21 95 [80,
110]
21 83 [74,
103]
21 82 [73,
97]
Post-op EEG
Interburst Interval
- Amplitude
32 0.11
(-0.25,
0.44)
0.56 32 0.01
(-0.34,
0.36)
0.95 32 0.01
(-0.34,
0.36)
0.96
Post-op EEG
Interburst Interval
- Duration
32 0.28
(-0.07,
0.58)
0.12 32 0.34
(-0.00,
0.62)
0.053 32 0.22
(-0.14,
0.53)
0.22
Post-op 24H EEG
Continuous
. No
. Yes
29 0.45 29 0.096 0.59
17 95 [80,
110]
17 97 [65,
103]
17 85 [64,
97]
12 90 [83,
95]
12 78 [74,
83]
12 75 [70,
85]
Post-op 24H EEG
Discontinuous
. No
29 0.45 29 0.096 0.59
12 90 [83,
95]
12 78 [74,
83]
12 75 [70,
85]
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. Yes 17 95 [80,
110]
17 97 [65,
103]
17 85 [64,
97]
Post-op 24H EEG
Sleep-wake cycle
. No
. Yes
29 0.079 29 0.11 0.36
19 95 [80,
110]
19 89 [74,
103]
19 82 [67,
100]
10 90 [65,
95]
10 76 [65,
83]
10 76 [64,
88]
Post-op 24H EEG
Interburst Interval
- Amplitude
29 -0.14
(-0.48,
0.24)
0.48 29 -0.34
(-0.63,
0.03)
0.070 29 -0.17
(-0.51,
0.21)
0.37
Post-op 24H EEG
Interburst Interval
- Duration
29 0.20
(-0.18,
0.53)
0.31 29 0.33
(-0.04,
0.62)
0.082 29 0.10
(-0.27,
0.45)
0.60
Severity of pre-op
EEG 32 0.01
(-0.34,
0.36)
0.95 32 0.12
(-0.24,
0.46)
0.51 32 0.00
(-0.35,
0.35)
0.99
Severity of post-
op EEG 32 0.09
(-0.27,
0.42)
0.64 32 0.12
(-0.24,
0.45)
0.51 32 0.02
(-0.33,
0.37)
0.90
Factor N Statistics P
value N Statistics P
value N Statistics P
value
Severity of post-
op 24H EEG 29 0.19 (-0.19,
0.52) 0.32 29 0.41
(0.05,
0.68)
0.026
29 0.16
(-0.22,
0.50)
0.41
Cross- clamp
time 32 0.04 (-0.25,
0.33) 0.78 32 0.32
(0.02,
0.56)
0.036
32 0.08
(-0.22,
0.36)
0.62
Arrest time 32 -0.00
(-0.30,
0.30)
0.99 32 0.13
(-0.19,
0.42)
0.43 32 -0.21
(-0.48,
0.10)
0.18
Bypass time 32 -0.05
(-0.33,
0.24)
0.75 32 0.24
(-0.06,
0.50)
0.12 32 -0.05
(-0.33,
0.24)
0.75
Statistics presented as Median [25th, 75th percentiles] with Kruskal-Wallis test or Spearman's correlation
(95% CI).
Overall neurocognitive outcomes for the cohort assessed by BSID -III are described in Table 2. Bayley
Scales of Infant and Toddler Development, Version 3 was administered at a median age of 17 months
(IQR 12–24). For the cognitive subtest, median scaled score was 8 (IQR 1.0–15). Median cognitive
Page 13/20
composite score was 90 (IQR 55–125). 13 neonates (38%) had an average cognitive score, where as 21%
had a low average score and 12% had extremely low composite score. Median language composite score
was 83 (IQR 47–135) with 9 neonates (27%) scoring an average score and 24% with an extremely low
score. On the motor subtest, median composite score was 78 (IQR 46–124), 26% of these neonates had
an average, borderline and extremely low scores respectively. We examined the association of various
components of EEG background activity with subtests of BSID-III – cognitive, language and motor (Table
3.). Pre-operative inter-burst interval amplitude and duration, immediate and 24-hour post-operative cEEG
background activity including continuity, excessive discontinuity, synchrony, inter-burst interval amplitude
and duration and presence or absence of sleep wake cycles were not associated with poor outcomes in
the cognitive and motor subtests of BSID- III (Table 3.). Pre-operative and immediate and 24 hour post-
operative severity of EEG ndings and encephalopathy as well as duration of cross- clamp time, bypass
time and arrest time were not associated poor cognitive or motor BSID-III scores at 12–24 months of age.
As shown in Table 3. Pre-operative inter-burst interval amplitude and background, immediate and 24 hour
post-operative background activity components on cEEG were not predictive of poor outcomes in the
language subtest. Severity of EEG classication and encephalopathy for the 24 hour post-operative EEG
was associated with a lower language composite score and was predictive of poor performance in the
language subtest of BSID-III (p = 0.026). Also, longer duration of cross clamp time was associated with
below average language composite scores during BSID-III testing at 12–24 months (p = 0.036).
Discussion
This study evaluated the role of cEEG background patterns, presence of sleep wake cycles and seizure
activity in the pre-operative and post-operative period to predict abnormal neurodevelopmental outcomes
at 12–24 months in neonates with CHD requiring cardiac surgery. In this retrospective study, we report
that 1) majority of infants with CHD that underwent surgical repair by 44 weeks GA had below average
scores in all three subtests (cognitive, language and motor) of BSID-III at 12–24 months of age 2)
Severity of encephalopathy classication for 24-hour postoperative EEG was predictive of poor language
composite scores during BSID-III) Longer duration of cross-clamp time was associated with below
average language composite score.
Our results demonstrated a higher rate (100%) of neurological abnormalities observed among the thirty-
four neonates that were included in the study and subsequently followed-up in the outpatient clinic. Most
common neurological abnormality in this study population was abnormal tone and developmental delay
(76%) followed by microcephaly (35%). Previous studies have demonstrated that more than 50% of
newborns with complex heart defects have clinical evidence of neurological impairments on exam before
surgery and these are subsequently risk factors for long term neurodevelopmental abnormalities. 27–29
Another study looking at 2 different forms of CPB for correction of TGA showed neurological impairment
in up to 37% of enrolled patients. 8 In our study, 67% of neonates with abnormal pre-operative MRI
demonstrated a nding of stroke. These ndings are similar to results demonstrated in previous studies.
30–34
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In this study population, median cross clamp time and CPB time was 50 minutes and 118 minutes
respectively (Table1.) Prolonged circulatory arrest time is a major risk factor for neurodevelopmental
impairments. 8,35 Follow-up studies in children who had undergone open heart surgery with periods of
arrest longer than 60 minutes and as short as 45 minutes showed associated neurodevelopmental
impairments. 50,51 In our cohort, longer duration cross-clamp time was associated with poor language
composite score on BSID-III assessment at 12–24 months of age (p = 0.036) (Table3.) Some previous
studies including the Boston circulatory Arrest Trial have provided evidence for the deleterious effects of
deep hypothermic circulatory arrest vs low ow CPB. 36–38
Factors contributing to neurologic and developmental impairment in infants with CHD are multifactorial
and comprises a complex interaction between preoperative, intraoperative and postoperative factors. 39
Also, neurodevelopmental dysfunction rates vary by disease complexity. 40 In our cohort, BSID-III was
administered at a median age of 17 months. The median cognitive composite score was 90 and 21%
neonates had below average cognitive scores. The median motor composite score was 78 and 67% of
these neonates had below average scores. Median language composite score was 83 with 66% of
neonates demonstrating below average scores (Table3.) Previous studies have demonstrated that mean
composite scores for Bayley III were slightly higher compared with composite scores for Bayley II. 41
Mean cognitive scores ranged from 91.0 to 104.8, mean language scores ranged from 87.8 to 97.0 and
mean motor scores ranged from 86.0 to 97.0.22, 25,42−43 Masoller et al in a case-control stud
demonstrated lower cognitive (91 vs 103), language (97 vs 108) and motor (86 vs 100). 45 Andropoulos
et al demonstrated composite scores for cognition (102 13.3), motor (89.6 14.1) and language (87.8
12.5) and no association between preoperative brain injury and neurodevelopmental outcomes. 46
EEG background activity has been shown to be an important measure of functional brain maturation and
impairment. 47 This study demonstrated that various components of cEEG background activity during
pre, immediate and 24-hour postoperative period was not associated with poor median cognitive
composite, language and motor composite scores. Severity of encephalopathy during pre, immediate and
24-hour postoperative EEG tracing was not predictive of lower cognitive and motor composite scores.
This is consistent with ndings of Gunn et al demonstrating no association between preoperative aEEG
background pattern and neurodevelopmental outcomes. 25 Similarly, Robertson et al showed no
association between EEG abnormalities, reduced cerebral blood ow and neurodevelopmental outcomes.
48 Severity of encephalopathy during the 24 hour postoperative period was associated with poor
language composite score on BSID-III (p = 0.026) (Table3.). Andropoulos et al reported lower language
scores associated with preoperative brain injury on MRI in infants with TGA who underwent cardiac
surgery. 44 Another study by William et al demonstrated a positive correlation between preoperative left
frontal polar and left frontal ß power and cognitive scores. 49 Hence, neonates with higher grades of
encephalopathy and severity on EEG in the immediate 24 hour postoperative period are at a higher risk of
poor language scores on BSID-III.
± ±
±
Page 15/20
This study has strengths and limitations. This study used continuous conventional 10-20system EEG for
neuromonitoring of neonates with CHD. Secondly, the study assessed various components of EEG
ndings and used this data to classify EEG background based on severity of encephalopathy. However,
this study has limitations too. Approximately 50% of neonates with CHD who underwent cardiac surgery
were lost to follow up and did not have Bayley assessment at 12–24 months of age. Although Bayley
Scales of Infant and Toddler Development-III provides an accurate assessment of a child’s developmental
status at 12–24 months, it has limited predictive value for later outcomes like intelligence quotient (IQ) or
behavioral issues in adolescence. This cohort study included a wide spectrum of CHD types having
different cEEG abnormalities further preventing subgroup analysis.
Conclusion
In this heterogeneous group of neonates with CHD who underwent repair by 44 weeks GA, majority of
neonates had below average cognitive, language and motor composite scores on BSID-III at 12–24
months of age. Longer duration of cross-clamp time was specically associated with poor language
composite scores. It is interesting to report a signicant association between severity of encephalopathy
during 24 hour postoperative EEG monitoring with poorer language composite scores on BSID-III
assessment. Early identication of high- risk infants is essential so that these infants would benet from
targeted early interventions to minimize neuromotor and behavioral decits in the future. Further studies
are needed to assess relationship between EEG background ndings and neurodevelopmental outcomes
in pre-school and school aged children with CHD.
Declarations
Additional information:
Conict of Interest:The authors declare no competing nancial interests.
Patient consent:No patient consent was required for this retrospective cohort study
Data availability statement:The datasets generated during and/or analyzed during the current study are
available from the corresponding author on reasonable request.
Funding:No nancial assistance was received in support of this study.
AuthorContributions Statement Page
Dr. Padiyar helped design the study, designed data collection instruments, collected data, drafted the
initial manuscript, reviewed and revised the manuscript.
Dr. Friedman conceptualized and designed the study and reviewed the manuscript.
Page 16/20
Dr. Pestana-Knight helped design the study, reviewed and revised the manuscript for important
intellectual content.
Linda Franic helped design data collection instruments and collected data.
Sarah Worley helped with data stratication and statistical analysis.
Dr. Aly, coordinated and supervised data collection, and critically reviewed the manuscript for important
intellectual content.
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Figures
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Figure 1
See image above for gure legend
