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Continuous Electroencephalogram (cEEG) Findings and Neurodevelopmental Outcomes in Neonates with Congenital Heart Disease (CHD) at 12-24 Months of Age

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Title: Continuous Electroencephalogram (cEEG) Findings and Neurodevelopmental Outcomes in Neonates with Congenital Heart Disease (CHD) at 12-24 Months of Age
Language: English
Authors: Swetha Padiyar (ORCID 0000-0002-7193-4631), Neil Friedman, Elia Pestana-Knight, Linda Franic, Sarah Worley, Hany Aly
Source: Journal of Autism and Developmental Disorders. 2025 55(9):3245-3256.
Availability: Springer. Available from: Springer Nature. One New York Plaza, Suite 4600, New York, NY 10004. Tel: 800-777-4643; Tel: 212-460-1500; Fax: 212-460-1700; e-mail: customerservice@springernature.com; Web site: https://link.springer.com/
Peer Reviewed: Y
Page Count: 12
Publication Date: 2025
Document Type: Journal Articles
Reports - Research
Descriptors: Brain, Diagnostic Tests, Heart Disorders, Neurodevelopmental Disorders, Infants, Toddlers, Child Development, Language Skills, Cognitive Ability, Psychomotor Skills
Geographic Terms: Ohio (Cleveland)
Assessment and Survey Identifiers: Bayley Scales of Infant and Toddler Development
DOI: 10.1007/s10803-024-06418-y
ISSN: 0162-3257
1573-3432
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) in children with congenital heart disease (CHD) undergoing cardiac surgery and its correlation with abnormal neurodevelopmental outcomes at 12-24 months on Bayley Scales of Infant and Toddler Development (BSID-III). Methods: 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 significant 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.
Abstractor: As Provided
Entry Date: 2025
Accession Number: EJ1481064
Database: ERIC
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  Value: <anid>AN0187434593;aut01sep.25;2025Aug22.05:47;v2.2.500</anid> <title id="AN0187434593-1">Continuous Electroencephalogram (cEEG) Findings and Neurodevelopmental Outcomes in Neonates with Congenital Heart Disease (CHD) at 12–24 Months of Age </title> <p>Objective: This study aims to assess the role of continuous EEG (cEEG) background patterns and duration of cross-clamp time and cardiopulmonary bypass (CPB) in children with congenital heart disease (CHD) undergoing cardiac surgery and its correlation with abnormal neurodevelopmental outcomes at 12–24 months on Bayley Scales of Infant and Toddler Development (BSID-III). Methods: 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 significant 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.</p> <p>Keywords: Congenital Heart Disease (CHD); Electroencephalogram (EEG); Neurodevelopmental outcomes; Medical and Health Sciences Clinical Sciences</p> <hd id="AN0187434593-2">Introduction</hd> <p>Congenital heart disease (CHD) encompasses both structural and non-structural anomalies present at birth.(Hoffman & Kaplan, [<reflink idref="bib17" id="ref1">17</reflink>]; Reller et al., [<reflink idref="bib41" id="ref2">41</reflink>]) 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.(Razzaghi et al., [<reflink idref="bib40" id="ref3">40</reflink>]) Neonates with CHD have an increased risk of brain injury. (Shillingford et al., [<reflink idref="bib45" id="ref4">45</reflink>]; Wernovsky et al., [<reflink idref="bib46" id="ref5">46</reflink>])The etiology of brain injury in neonates who undergo corrective surgery for CHD is multifactorial.(Meyer et al., [<reflink idref="bib35" id="ref6">35</reflink>]) Hypothesized etiologies include disturbances in brain metabolic function, brain injury, and abnormal brain development in addition to genetic predisposition.(Ransom & Srivastava, [<reflink idref="bib38" id="ref7">38</reflink>]) Neurodevelopmental disability after congenital cardiac surgery is common and is the most consequential sequelae of congenital heart disease (CHD).(Shillingford et al., [<reflink idref="bib45" id="ref8">45</reflink>]; Wernovsky et al., [<reflink idref="bib46" id="ref9">46</reflink>]) Recent literature shows higher risk of neurodevelopmental impairment such as difficulties with language, attention, academic achievement, fine and gross motor skills and psychological factors in this population. (Bellinger et al., [<reflink idref="bib3" id="ref10">3</reflink>]; Hövels-Gürich et al., [<reflink idref="bib20" id="ref11">20</reflink>]; Kirshbam et al., [<reflink idref="bib22" id="ref12">22</reflink>]; Mahle et al., [<reflink idref="bib28" id="ref13">28</reflink>]) 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.(Bellinger et al., [<reflink idref="bib3" id="ref14">3</reflink>]; Goldberg et al., [<reflink idref="bib11" id="ref15">11</reflink>]) 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.(Green, [<reflink idref="bib12" id="ref16">12</reflink>]) (Oster et al., [<reflink idref="bib37" id="ref17">37</reflink>]) 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 recommends long term EEG monitoring in neonates and infants with CHD that require early surgery.(Shellhaas et al., [<reflink idref="bib44" id="ref18">44</reflink>]) A previous study showed that only 55% of infants had normal pre-operative EEG. (C. et al., [<reflink idref="bib5" id="ref19">5</reflink>]) 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.(Chock et al., [<reflink idref="bib6" id="ref20">6</reflink>]; Clancy et al., [<reflink idref="bib7" id="ref21">7</reflink>], [<reflink idref="bib8" id="ref22">8</reflink>]; Gaynor et al., [<reflink idref="bib9" id="ref23">9</reflink>]; Gunn et al., [<reflink idref="bib14" id="ref24">14</reflink>]; Helmers et al., [<reflink idref="bib16" id="ref25">16</reflink>]; Newburger et al., [<reflink idref="bib36" id="ref26">36</reflink>]) 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 first 48 h in the post-operative period.(Rappaport et al., [<reflink idref="bib39" id="ref27">39</reflink>]) Also, increased mortality was significantly associated with occurrence of post-operative seizures and delay in recovery of the aEEG background pattern beyond 48 h.(Gunn et al., [<reflink idref="bib13" id="ref28">13</reflink>]) 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 various components of cEEG in the pre-operative and post-operative period and to correlate it with 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 cEEG findings after cardiac surgery and cognitive, language and motor scores on Bayley Scales of Infant and Toddler Development (BSID – III) at 12–24 months. We hypothesized that infants with CHD have abnormal pre-operative and post- operative cEEG findings and that these abnormalities were associated with poor outcomes in BSID- III scores at 12–24 months of age.</p> <hd id="AN0187434593-3">Methods</hd> <p></p> <hd id="AN0187434593-4">Study Population</hd> <p>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 identified. In our hospital, cEEG is a routine procedure for all infants with CHD prior to and after cardiac surgery. All infants with CHD undergoing surgical repair have a pre-operative and post-operative cranial US. In the past year, our institute had 141 live births with a cardiac diagnosis (42 infants with complex cardiac anomalies, 8 infants with fetal arrhythmia, 16 infants with cardiac function concerns and 75 infants with other cardiac anomalies including but not limited to VSDs, mild valvular stenosis, vascular rings, etc.). Our institute currently has three Pediatric cardiothoracic surgeons and over twenty pediatric cardiologists managing care for infants with CHD. 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, confirmed 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. All infants with CHD who underwent surgical correction were scheduled for outpatient follow up by pediatric neurologists to monitor neurodevelopmental outcomes in this high-risk population.</p> <hd id="AN0187434593-5">Continuous EEG (cEEG)</hd> <p>A 19-channel continuous cEEG recording was performed prior to and for at least 24 h after cardiac surgery. Pre-operatively, bedside EEG monitoring (BEM) recording was obtained for 24 h typically performed 1–2 days prior to 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 (modified for neonates) with collodion adhesive. 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.</p> <p>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 classified as normal or abnormal based on background patterns. Normal EEG background was defined as normal continuity and discontinuity (IBI < 4 s 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 classification of neonatal EEGs by Shellhaas et al., [<reflink idref="bib43" id="ref29">43</reflink>], [<reflink idref="bib44" id="ref30">44</reflink>] 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. (Shellhaas et al., [<reflink idref="bib43" id="ref31">43</reflink>], [<reflink idref="bib44" id="ref32">44</reflink>]) Sleep wake cycle was graded as normal or absent. Epileptic activity was classified 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 min 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 findings were noted, final decisions were made by a pediatric epileptologist. cEEG findings were described for the entire length of available recording for each neonate.</p> <hd id="AN0187434593-6">Bayley Scales of Infant and Toddler Development – 3rd Edition (BSID-III)</hd> <p>The Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) 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 five 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 fine motor skills). A mean composite score of 100 was considered within normal limit, with a standard deviation of 15. A score between 70 and 85 was considered as mild delay, scores between 55 and 70 as moderate delay and scores below 55 was classified as profound delay.</p> <hd id="AN0187434593-7">Clinical Parameters</hd> <p>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 first chest closure, days till first 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 h post operatively were also noted. Neonates were classified 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 classification of CHD.</p> <hd id="AN0187434593-8">Data Collection</hd> <p>Data were collected and managed using Research Electronic Data Capture (REDCap), a web based electronic application through Cleveland Clinic Children's Hospital.</p> <hd id="AN0187434593-9">Statistical Analysis</hd> <p>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 significance level of 0.05. Data were described using medians and ranges for continuous variables and counts and percentages for categorical variables. Associations of cEEG findings were assessed using non-parametric Kruskal-Wallis tests for categorical variables and Spearman rank correlations for continuous and ordinal findings. P- values of < 0.05 were considered to indicate statistical significance.</p> <hd id="AN0187434593-10">Results</hd> <p>A total of 98 patients with CHD who underwent surgical correction with CPB were identified. 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 final cohort consisted of 34 infants as shown in Fig. 1.</p> <p>Graph: Fig. 1 Flow diagram of the study population</p> <p>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 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 (1 infant had stroke and 5 infants had other abnormalities on post-operative cranial US) (Table 1.). In this study, only 3 patients had clinical or sub clinical seizures, of which 2 patients received anti-seizure medications.</p> <p>Table 1 Descriptive statistics, neurological status and classification of cardiac defects and surgical procedures for infants with congenital heart disease (<emph>N</emph> = 34)</p> <p> <ephtml> <table frame="hsides" rules="groups"><thead><tr><th align="left" /><th align="left" colspan="2"><p>Total (<italic>N</italic> = 34)</p></th></tr><tr><th align="left"><p>Factor</p></th><th align="left"><p><italic>N</italic></p></th><th align="left"><p>Statistics</p></th></tr></thead><tbody><tr><td align="left"><p>Sex, n (%)</p></td><td char="." align="char"><p>34</p></td><td align="left" /></tr><tr><td align="left"><p>Male</p></td><td align="left" /><td align="left"><p>21 (62)</p></td></tr><tr><td align="left"><p>Female</p></td><td align="left" /><td align="left"><p>13 (38)</p></td></tr><tr><td align="left"><p>Age at surgery (days), median (min, max)</p></td><td char="." align="char"><p>34</p></td><td align="left"><p>7.0 (0, 44)</p></td></tr><tr><td align="left"><p>Ethnicity, n (%)</p></td><td char="." align="char"><p>34</p></td><td align="left" /></tr><tr><td align="left"><p>Hispanic</p></td><td align="left" /><td align="left"><p>2 (5.9)</p></td></tr><tr><td align="left"><p>Non-Hispanic</p></td><td align="left" /><td align="left"><p>32 (94)</p></td></tr><tr><td align="left"><p>Gestation (Weeks), median (min, max)</p></td><td char="." align="char"><p>34</p></td><td align="left"><p>39 (36, 42)</p></td></tr><tr><td align="left"><p>Head circumference percentile at birth, median (min, max)</p></td><td char="." align="char"><p>33</p></td><td align="left"><p>36 (0.010, 100)</p></td></tr><tr><td align="left"><p>Weight percentile at birth, median (min, max)</p></td><td char="." align="char"><p>34</p></td><td align="left"><p>37 (0.010, 94)</p></td></tr><tr><td align="left"><p>ICU length of stay, median (min, max)</p></td><td char="." align="char"><p>34</p></td><td align="left"><p>13 (2.0, 69)</p></td></tr><tr><td align="left"><p>Total length of stay, median (min, max)</p></td><td char="." align="char"><p>34</p></td><td align="left"><p>24 (8.0, 218)</p></td></tr><tr><td align="left"><p>Deceased, n (%)</p></td><td char="." align="char"><p>34</p></td><td align="left"><p>1 (2.9)</p></td></tr><tr><td align="left"><p>Neurological status, n (%)</p></td><td char="." align="char"><p>34</p></td><td align="left" /></tr><tr><td align="left"><p>Abnormal</p></td><td align="left" /><td align="left"><p>34(100)</p></td></tr><tr><td align="left"><p>Type of neurological abnormality n (%)</p></td><td char="." align="char"><p>34</p></td><td align="left" /></tr><tr><td align="left"><p>Developmental delay</p></td><td char="." align="char"><p>34</p></td><td align="left"><p>26 (76)</p></td></tr><tr><td align="left"><p>Microcephaly</p></td><td char="." align="char"><p>34</p></td><td align="left"><p>12 (35)</p></td></tr><tr><td align="left"><p>Macrocephaly</p></td><td char="." align="char"><p>34</p></td><td align="left"><p>2 (5.9)</p></td></tr><tr><td align="left"><p>Stroke</p></td><td char="." align="char"><p>34</p></td><td align="left"><p>7 (21)</p></td></tr><tr><td align="left"><p>Motor apraxia/Coordination</p></td><td char="." align="char"><p>34</p></td><td align="left"><p>1 (2.9)</p></td></tr><tr><td align="left"><p>Behavioral/Emotional</p></td><td char="." align="char"><p>34</p></td><td align="left"><p>2 (5.9)</p></td></tr><tr><td align="left"><p>Seizures</p></td><td char="." align="char"><p>34</p></td><td align="left"><p>8 (24)</p></td></tr><tr><td align="left"><p>ADHD</p></td><td char="." align="char"><p>34</p></td><td align="left"><p>2 (5.9)</p></td></tr><tr><td align="left"><p>Other</p></td><td char="." align="char"><p>34</p></td><td align="left"><p>26 (76)</p></td></tr><tr><td align="left"><p>Pre-operative brain MRI abnormality, n (%) (MRI obtained in 3 patients)</p></td><td char="." align="char"><p>3</p></td><td align="left" /></tr><tr><td align="left"><p>Stroke</p></td><td align="left" /><td align="left"><p>2 (67)</p></td></tr><tr><td align="left"><p>Other</p></td><td align="left" /><td align="left"><p>1 (33)</p></td></tr><tr><td align="left"><p>Post-operative brain MRI abnormality, n (%) (MRI obtained in 2 patients)</p></td><td char="." align="char"><p>1</p></td><td align="left" /></tr><tr><td align="left"><p>Other</p></td><td align="left" /><td align="left"><p>1 (100)</p></td></tr><tr><td align="left"><p>Pre-operative head US abnormality, n (%) (head US obtained in 34 patients)</p></td><td char="." align="char"><p>5</p></td><td align="left" /></tr><tr><td align="left"><p>Other</p></td><td align="left" /><td align="left"><p>5 (100)</p></td></tr><tr><td align="left"><p>Post-operative head US abnormality, n (%) (head US obtained in 18 patients)</p></td><td char="." align="char"><p>6</p></td><td align="left" /></tr><tr><td align="left"><p>Stroke</p></td><td align="left" /><td align="left"><p>1 (17)</p></td></tr><tr><td align="left"><p>Other</p></td><td align="left" /><td align="left"><p>5 (83)</p></td></tr><tr><td align="left"><p>Class, n (%)</p></td><td char="." align="char"><p>34</p></td><td align="left" /></tr><tr><td align="left"><p>Two ventricles with no aortic arch obstruction (Class 1)</p></td><td align="left" /><td align="left"><p>14 (41)</p></td></tr><tr><td align="left"><p>Two ventricles with aortic arch obstruction (Class 2)</p></td><td align="left" /><td align="left"><p>6 (18)</p></td></tr><tr><td align="left"><p>One ventricle without arch obstruction (Class 3)</p></td><td align="left" /><td align="left"><p>6 (18)</p></td></tr><tr><td align="left"><p>One ventricle with arch obstruction (Class 4)</p></td><td align="left" /><td align="left"><p>8 (24)</p></td></tr><tr><td align="left"><p>Type of cardiac lesion/s</p></td><td align="left" /><td align="left" /></tr><tr><td align="left"><p>Single ventricle physiology (HLHS, DORV, DOLV)<sup>a</sup>, n (%)</p></td><td char="." align="char"><p>34</p></td><td align="left"><p>14 (41)</p></td></tr><tr><td align="left"><p>Tetralogy of Fallot, n (%)</p></td><td char="." align="char"><p>34</p></td><td align="left"><p>1 (2.9)</p></td></tr><tr><td align="left"><p>Transposition of great arteries, n (%)</p></td><td char="." align="char"><p>34</p></td><td align="left"><p>13 (38)</p></td></tr><tr><td align="left"><p>AV canal, n (%)</p></td><td char="." align="char"><p>34</p></td><td align="left"><p>1 (2.9)</p></td></tr><tr><td align="left"><p>Heterotaxy, n (%)</p></td><td char="." align="char"><p>34</p></td><td align="left"><p>0 (0)</p></td></tr><tr><td align="left"><p>Atrial septal defect, n (%)</p></td><td char="." align="char"><p>34</p></td><td align="left"><p>8 (24)</p></td></tr><tr><td align="left"><p>Ventricular septal defect, n (%)</p></td><td char="." align="char"><p>34</p></td><td align="left"><p>6 (18)</p></td></tr><tr><td align="left"><p>Other, n (%)</p></td><td char="." align="char"><p>34</p></td><td align="left"><p>26 (76)</p></td></tr><tr><td align="left"><p>Type of surgery, n (%)</p></td><td char="." align="char"><p>34</p></td><td align="left" /></tr><tr><td align="left"><p>Single ventricular repair</p></td><td align="left" /><td align="left"><p>14 (41)</p></td></tr><tr><td align="left"><p>Biventricular repair</p></td><td align="left" /><td align="left"><p>20 (59)</p></td></tr><tr><td align="left"><p>STAT<sup>b</sup> Category, n (%)</p></td><td char="." align="char"><p>34</p></td><td align="left" /></tr><tr><td align="left"><p>1</p></td><td align="left" /><td align="left"><p>3 (8.8)</p></td></tr><tr><td align="left"><p>2</p></td><td align="left" /><td align="left"><p>2 (5.9)</p></td></tr><tr><td align="left"><p>3</p></td><td align="left" /><td align="left"><p>11 (32)</p></td></tr><tr><td align="left"><p>4</p></td><td align="left" /><td align="left"><p>8 (24)</p></td></tr><tr><td align="left"><p>5</p></td><td align="left" /><td align="left"><p>10 (29)</p></td></tr><tr><td align="left"><p>Cross clamp time (minutes), median (min, max)</p></td><td char="." align="char"><p>34</p></td><td align="left"><p>50 (0, 81)</p></td></tr><tr><td align="left"><p>Length of time on bypass (minutes), median (min, max)</p></td><td char="." align="char"><p>34</p></td><td align="left"><p>117 (0, 166)</p></td></tr><tr><td align="left"><p>Did patient require ECMO<sup>c</sup> within 7 days of surgery, n (%)</p></td><td char="." align="char"><p>34</p></td><td align="left" /></tr><tr><td align="left"><p>No</p></td><td align="left" /><td align="left"><p>32 (94)</p></td></tr><tr><td align="left"><p>Yes</p></td><td align="left" /><td align="left"><p>2 (5.9)</p></td></tr><tr><td align="left"><p>Days of ECMO, n (%)</p></td><td char="." align="char"><p>5</p></td><td align="left" /></tr><tr><td align="left"><p>2</p></td><td align="left" /><td align="left"><p>3 (60)</p></td></tr><tr><td align="left"><p>3</p></td><td align="left" /><td align="left"><p>1 (20)</p></td></tr><tr><td align="left"><p>4</p></td><td align="left" /><td align="left"><p>1 (20)</p></td></tr><tr><td align="left"><p>Sedation, n (%)</p></td><td char="." align="char"><p>34</p></td><td align="left" /></tr><tr><td align="left"><p>Yes</p></td><td align="left" /><td align="left"><p>32 (100)</p></td></tr><tr><td align="left"><p>Paralysis, n (%)</p></td><td char="." align="char"><p>34</p></td><td align="left" /></tr><tr><td align="left"><p>No</p></td><td align="left" /><td align="left"><p>30 (88)</p></td></tr><tr><td align="left"><p>Yes</p></td><td align="left" /><td align="left"><p>4 (12)</p></td></tr></tbody></table> </ephtml> </p> <p>Statistics presented as Median (min, max), N (column %). <sups>a</sups> HLHS- Hypoplastic left heart syndrome, DORV- Double outlet right ventricle, DOLV- Double outlet left ventricle <sups>b</sups> The Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery <sups>c</sups> ECMO- Extracorporeal membrane oxygenation</p> <p>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 1. The median duration of CPB was 117 min (IQR 0-166) and cross clamp time was 50 min (IQR 0–81). Two neonates (5.9%) were placed on ECMO with 20% requiring ECMO for 2 days and 20% neonates for 3 days. Both the neonates requiring ECMO had normal pre and post-operative cranial US findings, abnormal pre-operative EEG findings (mild encephalopathy) and post-operative EEG findings (moderate-severe encephalopathy). One of the infants who required ECMO with single ventricular physiology had seizures and developmental delay noted during BSID-III assessment (low cognitive, language and motor composite scores).</p> <hd id="AN0187434593-11">Neurodevelopmental Assessment Scores</hd> <p>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 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.</p> <p>Table 2 Descriptive statistics for neurodevelopmental outcomes at 12–24 months</p> <p> <ephtml> <table frame="hsides" rules="groups"><thead><tr><th align="left" /><th align="left" colspan="2"><p>Total (<italic>N</italic> = 34)</p></th></tr><tr><th align="left"><p>Factor</p></th><th align="left"><p><italic>N</italic></p></th><th align="left"><p>Statistics</p></th></tr></thead><tbody><tr><td align="left"><p>Age at BSID<sup>a</sup> (months), median (min, max)</p></td><td char="." align="char"><p>34</p></td><td align="left"><p>17 (12, 24)</p></td></tr><tr><td align="left"><p>BSID Cognitive Scaled, median (min, max)</p></td><td char="." align="char"><p>34</p></td><td align="left"><p>8.0 (1.0, 15)</p></td></tr><tr><td align="left"><p>BSID Cognitive Composite, median (min, max)</p></td><td char="." align="char"><p>34</p></td><td align="left"><p>90 (55, 125)</p></td></tr><tr><td align="left"><p>BSID Cognitive Percentile, median (min, max)</p></td><td char="." align="char"><p>34</p></td><td align="left"><p>25 (0.10, 95)</p></td></tr><tr><td align="left"><p>BSID Cognitive Category, n (%)</p></td><td char="." align="char"><p>34</p></td><td align="left" /></tr><tr><td align="left"><p>Extremely Low</p></td><td align="left" /><td align="left"><p>4 (12)</p></td></tr><tr><td align="left"><p>Borderline</p></td><td align="left" /><td align="left"><p>3 (8.8)</p></td></tr><tr><td align="left"><p>Low Average</p></td><td align="left" /><td align="left"><p>7 (21)</p></td></tr><tr><td align="left"><p>Average</p></td><td align="left" /><td align="left"><p>13 (38)</p></td></tr><tr><td align="left"><p>High Average</p></td><td align="left" /><td align="left"><p>4 (12)</p></td></tr><tr><td align="left"><p>Superior</p></td><td align="left" /><td align="left"><p>3 (8.8)</p></td></tr><tr><td align="left"><p>BSID Language Scaled, median (min, max)</p></td><td char="." align="char"><p>33</p></td><td align="left"><p>14 (2.0, 32)</p></td></tr><tr><td align="left"><p>BSID Language Composite, median (min, max)</p></td><td char="." align="char"><p>33</p></td><td align="left"><p>83 (47, 135)</p></td></tr><tr><td align="left"><p>BSID Language Percentile, median (min, max)</p></td><td char="." align="char"><p>33</p></td><td align="left"><p>13 (0.10, 99)</p></td></tr><tr><td align="left"><p>BSID Language Category, n (%)</p></td><td char="." align="char"><p>33</p></td><td align="left" /></tr><tr><td align="left"><p>Extremely Low</p></td><td align="left" /><td align="left"><p>8 (24)</p></td></tr><tr><td align="left"><p>Borderline</p></td><td align="left" /><td align="left"><p>7 (21)</p></td></tr><tr><td align="left"><p>Low Average</p></td><td align="left" /><td align="left"><p>7 (21)</p></td></tr><tr><td align="left"><p>Average</p></td><td align="left" /><td align="left"><p>9 (27)</p></td></tr><tr><td align="left"><p>High Average</p></td><td align="left" /><td align="left"><p>1 (3.0)</p></td></tr><tr><td align="left"><p>Very Superior</p></td><td align="left" /><td align="left"><p>1 (3.0)</p></td></tr><tr><td align="left"><p>BSID Motor Scaled, median (min, max)</p></td><td char="." align="char"><p>34</p></td><td align="left"><p>13 (2.0, 28)</p></td></tr><tr><td align="left"><p>BSID Motor Composite, median (min, max)</p></td><td char="." align="char"><p>34</p></td><td align="left"><p>78 (46, 124)</p></td></tr><tr><td align="left"><p>BSID Motor Percentile, median (min, max)</p></td><td char="." align="char"><p>34</p></td><td align="left"><p>6.5 (0.10, 95)</p></td></tr><tr><td align="left"><p>BSID Motor Category, n (%)</p></td><td char="." align="char"><p>34</p></td><td align="left" /></tr><tr><td align="left"><p>Extremely Low</p></td><td align="left" /><td align="left"><p>9 (26)</p></td></tr><tr><td align="left"><p>Borderline</p></td><td align="left" /><td align="left"><p>9 (26)</p></td></tr><tr><td align="left"><p>Low Average</p></td><td align="left" /><td align="left"><p>5 (15)</p></td></tr><tr><td align="left"><p>Average</p></td><td align="left" /><td align="left"><p>9 (26)</p></td></tr><tr><td align="left"><p>High Average</p></td><td align="left" /><td align="left"><p>1 (2.9)</p></td></tr><tr><td align="left"><p>Superior</p></td><td align="left" /><td align="left"><p>1 (2.9)</p></td></tr></tbody></table> </ephtml> </p> <p>Statistics presented as Median (min, max), N (column %). <sups>a</sups> BSID Bayley Scale of Infant Development</p> <hd id="AN0187434593-12">Correlation of cEEG Components with BSID-III Subtests</hd> <p>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.).</p> <p>Table 3 Correlation of cEEG with cognitive, language and motor composite score (CS) at 12–24 months</p> <p> <ephtml> <table frame="hsides" rules="groups"><thead><tr><th align="left" /><th align="left" colspan="4"><p>Cognitive composite score</p></th><th align="left" colspan="3"><p>Language composite score</p></th><th align="left" colspan="3"><p>Motor composite score</p></th></tr><tr><th align="left"><p>Factor</p></th><th align="left"><p><italic>N</italic></p></th><th align="left" colspan="2"><p>Statistics</p></th><th align="left"><p><italic>P</italic> value</p></th><th align="left"><p><italic>N</italic></p></th><th align="left"><p>Statistics</p></th><th align="left"><p><italic>P</italic> value</p></th><th align="left"><p><italic>N</italic></p></th><th align="left"><p>Statistics</p></th><th align="left"><p><italic>P</italic> value</p></th></tr></thead><tbody><tr><td align="left"><p>Pre-op EEG Interburst Interval - Amplitude</p></td><td align="left"><p>32</p></td><td align="left" colspan="2"><p>0.09 (-0.27, 0.43)</p></td><td align="left"><p>0.62</p></td><td align="left"><p>32</p></td><td align="left"><p>-0.06 (-0.40, 0.30)</p></td><td align="left"><p>0.76</p></td><td align="left"><p>32</p></td><td align="left"><p>0.04 (-0.32, 0.38)</p></td><td align="left"><p>0.84</p></td></tr><tr><td align="left"><p>Pre-op EEG Interburst Interval – Duration</p></td><td align="left"><p>32</p></td><td align="left" colspan="2"><p>-0.08 (-0.42, 0.28)</p></td><td align="left"><p>0.67</p></td><td align="left"><p>32</p></td><td align="left"><p>-0.04 (-0.39, 0.32)</p></td><td align="left"><p>0.85</p></td><td align="left"><p>32</p></td><td align="left"><p>-0.13 (-0.46, 0.23)</p></td><td align="left"><p>0.48</p></td></tr><tr><td align="left"><p>Post-op EEG Continuous</p></td><td align="left"><p>32</p></td><td align="left" colspan="2" /><td align="left"><p>0.26</p></td><td align="left"><p>32</p></td><td align="left" /><td align="left"><p>0.066</p></td><td align="left" /><td align="left" /><td align="left"><p>0.45</p></td></tr><tr><td align="left"><p>No</p></td><td align="left"><p>17</p></td><td align="left" colspan="2"><p>95 [80, 110]</p></td><td align="left" /><td align="left"><p>17</p></td><td align="left"><p>89 [77, 103]</p></td><td align="left" /><td align="left"><p>17</p></td><td align="left"><p>82 [67, 97]</p></td><td align="left" /></tr><tr><td align="left"><p>Yes</p></td><td align="left"><p>15</p></td><td align="left" colspan="2"><p>90 [75, 95]</p></td><td align="left" /><td align="left"><p>15</p></td><td align="left"><p>77 [62, 94]</p></td><td align="left" /><td align="left"><p>15</p></td><td align="left"><p>73 [70, 91]</p></td><td align="left" /></tr><tr><td align="left"><p>Post-op EEG Discontinuous</p></td><td align="left"><p>32</p></td><td align="left" colspan="2" /><td align="left"><p>0.21</p></td><td align="left"><p>32</p></td><td align="left" /><td align="left"><p>0.065</p></td><td align="left" /><td align="left" /><td align="left"><p>0.54</p></td></tr><tr><td align="left"><p>No</p></td><td align="left"><p>14</p></td><td align="left" colspan="2"><p>90 [75, 95]</p></td><td align="left" /><td align="left"><p>14</p></td><td align="left"><p>76 [62, 94]</p></td><td align="left" /><td align="left"><p>14</p></td><td align="left"><p>76 [70, 91]</p></td><td align="left" /></tr><tr><td align="left"><p>Yes</p></td><td align="left"><p>18</p></td><td align="left" colspan="2"><p>95 [80, 110]</p></td><td align="left" /><td align="left"><p>18</p></td><td align="left"><p>88 [77, 103]</p></td><td align="left" /><td align="left"><p>18</p></td><td align="left"><p>82 [67, 97]</p></td><td align="left" /></tr><tr><td align="left"><p>Post-op EEG Synchronous</p></td><td align="left"><p>32</p></td><td align="left" colspan="2" /><td align="left"><p>0.37</p></td><td align="left" /><td align="left" /><td align="left"><p>0.27</p></td><td align="left" /><td align="left" /><td align="left"><p>0.60</p></td></tr><tr><td align="left"><p>No</p></td><td align="left"><p>11</p></td><td align="left" colspan="2"><p>90 [80, 95]</p></td><td align="left" /><td align="left"><p>11</p></td><td align="left"><p>83 [59, 94]</p></td><td align="left" /><td align="left"><p>11</p></td><td align="left"><p>73 [64, 97]</p></td><td align="left" /></tr><tr><td align="left"><p>Yes</p></td><td align="left"><p>21</p></td><td align="left" colspan="2"><p>95 [80, 110]</p></td><td align="left" /><td align="left"><p>21</p></td><td align="left"><p>83 [74, 103]</p></td><td align="left" /><td align="left"><p>21</p></td><td align="left"><p>82 [73, 97]</p></td><td align="left" /></tr><tr><td align="left"><p>Post-op EEG Interburst Interval - Amplitude</p></td><td align="left"><p>32</p></td><td align="left" colspan="2"><p>0.11 (-0.25, 0.44)</p></td><td align="left"><p>0.56</p></td><td align="left"><p>32</p></td><td align="left"><p>0.01 (-0.34, 0.36)</p></td><td align="left"><p>0.95</p></td><td align="left"><p>32</p></td><td align="left"><p>0.01 (-0.34, 0.36)</p></td><td align="left"><p>0.96</p></td></tr><tr><td align="left"><p>Post-op EEG Interburst Interval - Duration</p></td><td align="left"><p>32</p></td><td align="left" colspan="2"><p>0.28 (-0.07, 0.58)</p></td><td align="left"><p>0.12</p></td><td align="left"><p>32</p></td><td align="left"><p>0.34 (-0.00, 0.62)</p></td><td align="left"><p>0.053</p></td><td align="left"><p>32</p></td><td align="left"><p>0.22 (-0.14, 0.53)</p></td><td align="left"><p>0.22</p></td></tr><tr><td align="left"><p>Post-op 24 H EEG Continuous</p></td><td align="left"><p>29</p></td><td align="left" colspan="2" /><td align="left"><p>0.45</p></td><td align="left"><p>29</p></td><td align="left" /><td align="left"><p>0.096</p></td><td align="left" /><td align="left" /><td align="left"><p>0.59</p></td></tr><tr><td align="left"><p>No</p></td><td align="left"><p>17</p></td><td align="left" colspan="2"><p>95 [80, 110]</p></td><td align="left" /><td align="left"><p>17</p></td><td align="left"><p>97 [65, 103]</p></td><td align="left" /><td align="left"><p>17</p></td><td align="left"><p>85 [64, 97]</p></td><td align="left" /></tr><tr><td align="left"><p>Yes</p></td><td align="left"><p>12</p></td><td align="left" colspan="2"><p>90 [83, 95]</p></td><td align="left" /><td align="left"><p>12</p></td><td align="left"><p>78 [74, 83]</p></td><td align="left" /><td align="left"><p>12</p></td><td align="left"><p>75 [70, 85]</p></td><td align="left" /></tr><tr><td align="left"><p>Post-op 24 H EEG Discontinuous</p></td><td align="left"><p>29</p></td><td align="left" colspan="2" /><td align="left"><p>0.45</p></td><td align="left"><p>29</p></td><td align="left" /><td align="left"><p>0.096</p></td><td align="left" /><td align="left" /><td align="left"><p>0.59</p></td></tr><tr><td align="left"><p>No</p></td><td align="left"><p>12</p></td><td align="left" colspan="2"><p>90 [83, 95]</p></td><td align="left" /><td align="left"><p>12</p></td><td align="left"><p>78 [74, 83]</p></td><td align="left" /><td align="left"><p>12</p></td><td align="left"><p>75 [70, 85]</p></td><td align="left" /></tr><tr><td align="left"><p>Yes</p></td><td align="left"><p>17</p></td><td align="left" colspan="2"><p>95 [80, 110]</p></td><td align="left" /><td align="left"><p>17</p></td><td align="left"><p>97 [65, 103]</p></td><td align="left" /><td align="left"><p>17</p></td><td align="left"><p>85 [64, 97]</p></td><td align="left" /></tr><tr><td align="left"><p>Post-op 24 H EEG Sleep-wake cycle</p></td><td align="left"><p>29</p></td><td align="left" colspan="2" /><td align="left"><p>0.079</p></td><td align="left"><p>29</p></td><td align="left" /><td align="left"><p>0.11</p></td><td align="left" /><td align="left" /><td align="left"><p>0.36</p></td></tr><tr><td align="left"><p>No</p></td><td align="left"><p>19</p></td><td align="left" colspan="2"><p>95 [80, 110]</p></td><td align="left" /><td align="left"><p>19</p></td><td align="left"><p>89 [74, 103]</p></td><td align="left" /><td align="left"><p>19</p></td><td align="left"><p>82 [67, 100]</p></td><td align="left" /></tr><tr><td align="left"><p>Yes</p></td><td align="left"><p>10</p></td><td align="left" colspan="2"><p>90 [65, 95]</p></td><td align="left" /><td align="left"><p>10</p></td><td align="left"><p>76 [65, 83]</p></td><td align="left" /><td align="left"><p>10</p></td><td align="left"><p>76 [64, 88]</p></td><td align="left" /></tr><tr><td align="left"><p>Post-op 24 H EEG Interburst Interval - Amplitude</p></td><td align="left"><p>29</p></td><td align="left" colspan="2"><p>-0.14 (-0.48, 0.24)</p></td><td align="left"><p>0.48</p></td><td align="left"><p>29</p></td><td align="left"><p>-0.34 (-0.63, 0.03)</p></td><td align="left"><p>0.070</p></td><td align="left"><p>29</p></td><td align="left"><p>-0.17 (-0.51, 0.21)</p></td><td align="left"><p>0.37</p></td></tr><tr><td align="left"><p>Post-op 24 H EEG Interburst Interval - Duration</p></td><td align="left"><p>29</p></td><td align="left" colspan="2"><p>0.20 (-0.18, 0.53)</p></td><td align="left"><p>0.31</p></td><td align="left"><p>29</p></td><td align="left"><p>0.33 (-0.04, 0.62)</p></td><td align="left"><p>0.082</p></td><td align="left"><p>29</p></td><td align="left"><p>0.10 (-0.27, 0.45)</p></td><td align="left"><p>0.60</p></td></tr><tr><td align="left"><p>Severity of pre-op EEG</p></td><td align="left"><p>32</p></td><td align="left" colspan="2"><p>0.01 (-0.34, 0.36)</p></td><td align="left"><p>0.95</p></td><td align="left"><p>32</p></td><td align="left"><p>0.12 (-0.24, 0.46)</p></td><td align="left"><p>0.51</p></td><td align="left"><p>32</p></td><td align="left"><p>0.00 (-0.35, 0.35)</p></td><td align="left"><p>0.99</p></td></tr><tr><td align="left"><p>Severity of post-op EEG</p></td><td align="left"><p>32</p></td><td align="left" colspan="2"><p>0.09 (-0.27, 0.42)</p></td><td align="left"><p>0.64</p></td><td align="left"><p>32</p></td><td align="left"><p>0.12 (-0.24, 0.45)</p></td><td align="left"><p>0.51</p></td><td align="left"><p>32</p></td><td align="left"><p>0.02 (-0.33, 0.37)</p></td><td align="left"><p>0.90</p></td></tr><tr><td align="left"><p>Severity of post-op 24 H EEG</p></td><td align="left"><p>29</p></td><td align="left"><p>0.19 (-0.19, 0.52)</p></td><td align="left" colspan="2"><p>0.32</p></td><td align="left"><p>29</p></td><td align="left"><p>0.41 (0.05, 0.68)</p></td><td align="left"><p><bold><italic>0.026</italic></bold></p></td><td align="left"><p>29</p></td><td align="left"><p>0.16 (-0.22, 0.50)</p></td><td align="left"><p>0.41</p></td></tr><tr><td align="left"><p>Cross- clamp time</p></td><td align="left"><p>32</p></td><td align="left"><p>0.04 (-0.25, 0.33)</p></td><td align="left" colspan="2"><p>0.78</p></td><td align="left"><p>32</p></td><td align="left"><p>0.32 (0.02, 0.56)</p></td><td align="left"><p><bold><italic>0.036</italic></bold></p></td><td align="left"><p>32</p></td><td align="left"><p>0.08 (-0.22, 0.36)</p></td><td align="left"><p>0.62</p></td></tr><tr><td align="left"><p>Arrest time</p></td><td align="left"><p>32</p></td><td align="left"><p>-0.00 (-0.30, 0.30)</p></td><td align="left" colspan="2"><p>0.99</p></td><td align="left"><p>32</p></td><td align="left"><p>0.13 (-0.19, 0.42)</p></td><td align="left"><p>0.43</p></td><td align="left"><p>32</p></td><td align="left"><p>-0.21 (-0.48, 0.10)</p></td><td align="left"><p>0.18</p></td></tr><tr><td align="left"><p>Bypass time</p></td><td align="left"><p>32</p></td><td align="left"><p>-0.05 (-0.33, 0.24)</p></td><td align="left" colspan="2"><p>0.75</p></td><td align="left"><p>32</p></td><td align="left"><p>0.24 (-0.06, 0.50)</p></td><td align="left"><p>0.12</p></td><td align="left"><p>32</p></td><td align="left"><p>-0.05 (-0.33, 0.24)</p></td><td align="left"><p>0.75</p></td></tr></tbody></table> </ephtml> </p> <p>Statistics presented as Median [25th, 75th percentiles] with Kruskal-Wallis test or Spearman's correlation (95% CI).</p> <hd id="AN0187434593-13">Correlation of cEEG and Cognitive and Motor Subtests of BSID-III</hd> <p>Pre-operative and immediate and 24 h post-operative severity of EEG findings 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.</p> <hd id="AN0187434593-14">Correlation of cEEG and Language Subtest of BSID-III</hd> <p>As shown in Table 3. Pre-operative inter-burst interval amplitude and background, immediate and 24 h post-operative background activity components on cEEG did not correlate with poor outcomes in the language subtest. Severity of EEG classification and encephalopathy for the 24 h post-operative EEG was associated with a lower language composite score and correlated with poor performance in the language subtest of BSID-III (<emph>p</emph> = 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 (<emph>p</emph> = 0.036).</p> <p>Degree of functional myocardial dysfunction in this cohort was assessed using clinical evaluation tool – Vasoactive -inotropic score (VIS). Max VIS (median) at 24 h and 48 h post-operatively was 8.5 and 6.0 respectively. Higher VIS was associated with lack of sleep wake cycling in the post-operative period (p 0.024), longer duration of CPB (p 0.013), longer duration on IBI amplitude (p 0.017) and severity of encephalopathy (<emph>p</emph> < 0.001) during pre-operative EEG recording (Table 4.). There was so significant association of VIS post-operatively with neurodevelopmental outcomes assessed by BSID-III in this cohort.</p> <p>Table 4 Vasoactive inotropic score (VIS) at 24 h post op vs. EEG</p> <p> <ephtml> <table frame="hsides" rules="groups"><thead><tr><th align="left"><p>Factor</p></th><th align="left"><p><italic>N</italic></p></th><th align="left"><p>Statistics</p></th><th align="left"><p><italic>p</italic>-value</p></th></tr></thead><tbody><tr><td align="left"><p>Post-op 24 H EEG Continuous</p></td><td align="left" /><td align="left" /><td align="left"><p>0.30</p></td></tr><tr><td align="left"><p>No</p></td><td align="left"><p>17</p></td><td align="left"><p>9.0 [5.0, 15]</p></td><td align="left" /></tr><tr><td align="left"><p>Yes</p></td><td align="left"><p>12</p></td><td align="left"><p>15 [6.0, 20]</p></td><td align="left" /></tr><tr><td align="left"><p>Post-op 24 H EEG Discontinuous</p></td><td align="left" /><td align="left" /><td align="left"><p>0.30</p></td></tr><tr><td align="left"><p>No</p></td><td align="left"><p>12</p></td><td align="left"><p>15 [6.0, 20]</p></td><td align="left" /></tr><tr><td align="left"><p>Yes</p></td><td align="left"><p>17</p></td><td align="left"><p>9.0 [5.0, 15]</p></td><td align="left" /></tr><tr><td align="left"><p>Post-op 24 H EEG Sleep-wake cycle</p></td><td align="left" /><td align="left" /><td align="left"><p><bold><italic>0.024</italic></bold></p></td></tr><tr><td align="left"><p>No</p></td><td align="left"><p>19</p></td><td align="left"><p>14 [7.0, 22]</p></td><td align="left" /></tr><tr><td align="left"><p>Yes</p></td><td align="left"><p>10</p></td><td align="left"><p>5.0 [2.5, 13]</p></td><td align="left" /></tr><tr><td align="left"><p>Length of Time on Bypass (Minutes)</p></td><td align="left"><p>34</p></td><td align="left"><p>0.42 (0.09, 0.66)</p></td><td align="left"><p><bold><italic>0.013</italic></bold></p></td></tr><tr><td align="left"><p>Circulatory Arrest Time (Min)</p></td><td align="left"><p>34</p></td><td align="left"><p>0.28 (-0.07, 0.57)</p></td><td align="left"><p>0.12</p></td></tr><tr><td align="left"><p>Cross Clamp Time (Mins)</p></td><td align="left"><p>34</p></td><td align="left"><p>-0.02 (-0.35, 0.32)</p></td><td align="left"><p>0.92</p></td></tr><tr><td align="left"><p>Post-op 24 H EEG Interburst Interval - Amplitude</p></td><td align="left"><p>29</p></td><td align="left"><p>-0.28 (-0.59, 0.09)</p></td><td align="left"><p>0.14</p></td></tr><tr><td align="left"><p>Post-op 24 H EEG Interburst Interval - Duration</p></td><td align="left"><p>29</p></td><td align="left"><p>0.32 (-0.05, 0.62)</p></td><td align="left"><p>0.087</p></td></tr><tr><td align="left"><p>Pre-op EEG Interburst Interval - Amplitude</p></td><td align="left"><p>32</p></td><td align="left"><p>-0.42 (-0.67, -0.08)</p></td><td align="left"><p><bold><italic>0.017</italic></bold></p></td></tr><tr><td align="left"><p>Pre-op EEG Interburst Interval - Duration</p></td><td align="left"><p>32</p></td><td align="left"><p>0.25 (-0.11, 0.55)</p></td><td align="left"><p>0.17</p></td></tr><tr><td align="left"><p>Severity of post-op EEG</p></td><td align="left"><p>32</p></td><td align="left"><p>-0.18 (-0.49, 0.18)</p></td><td align="left"><p>0.34</p></td></tr><tr><td align="left"><p>Severity of post-op 24 H EEG</p></td><td align="left"><p>29</p></td><td align="left"><p>0.06 (-0.31, 0.42)</p></td><td align="left"><p>0.75</p></td></tr><tr><td align="left"><p>Severity of pre-op EEG</p></td><td align="left"><p>32</p></td><td align="left"><p>0.68 (0.44, 0.83)</p></td><td align="left"><p><bold><italic>< 0.001</italic></bold></p></td></tr></tbody></table> </ephtml> </p> <p>Statistics presented as Median [25th, 75th percentiles] with Kruskal-Wallis test or Spearman's correlation (95% CI).</p> <hd id="AN0187434593-15">Discussion</hd> <p>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 and its correlation to abnormal neurodevelopmental outcomes at 12–24 months in neonates with CHD requiring cardiac surgery. In this retrospective study, we report that (<reflink idref="bib1" id="ref33">1</reflink>) 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 (<reflink idref="bib2" id="ref34">2</reflink>) Severity of encephalopathy classification for 24-hour postoperative EEG was correlating with poor language composite scores during BSID-III) Longer duration of cross-clamp time was associated with below average language composite score.</p> <p>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. (Gaynor et al., [<reflink idref="bib10" id="ref35">10</reflink>]; Hövels-Gürich et al., [<reflink idref="bib19" id="ref36">19</reflink>]; Limperopoulos et al., [<reflink idref="bib26" id="ref37">26</reflink>]) Another study looking at 2 different forms of CPB for correction of TGA showed neurological impairment in up to 37% of enrolled patients. (Bellinger et al., [<reflink idref="bib3" id="ref38">3</reflink>]) A higher rate of neurological abnormalities observed among neonates compared to previous studies could be due to the smaller sample size and nature of cardiac defects of neonates included in this study. In our study, 67% of neonates with abnormal pre-operative MRI demonstrated a finding of stroke. These findings are similar to results demonstrated in previous studies. (Khalil et al., [<reflink idref="bib21" id="ref39">21</reflink>]; Latal et al., [<reflink idref="bib24" id="ref40">24</reflink>]; Licht et al., [<reflink idref="bib25" id="ref41">25</reflink>]; Mahle et al., [<reflink idref="bib29" id="ref42">29</reflink>]; McQuillen et al., [<reflink idref="bib33" id="ref43">33</reflink>])</p> <p>In this study population, median cross clamp time and CPB time was 50 min and 118 min respectively. Prolonged circulatory arrest time is a major risk factor for neurodevelopmental impairments. (Bellinger et al., [<reflink idref="bib3" id="ref44">3</reflink>]; Limperopoulos et al., [<reflink idref="bib27" id="ref45">27</reflink>]) Follow-up studies in children who had undergone open heart surgery with periods of arrest longer than 60 min and as short as 45 min showed associated neurodevelopmental impairments. <sups>50,51</sups> 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. Some previous studies including the Boston circulatory Arrest Trial have provided evidence for the deleterious effects of deep hypothermic circulatory arrest vs. low flow CPB (Bellinger et al., [<reflink idref="bib4" id="ref46">4</reflink>]; H.H. et al., [<reflink idref="bib15" id="ref47">15</reflink>]; Hovels-Gurich et al., [<reflink idref="bib18" id="ref48">18</reflink>]).</p> <p>Factors contributing to neurologic and developmental impairment in infants with CHD are multifactorial and comprises a complex interaction between preoperative, intraoperative and postoperative factors. (Majnemer & Limperopoulos, [<reflink idref="bib30" id="ref49">30</reflink>]) Also, neurodevelopmental dysfunction rates vary by disease complexity. (Martinez-Biarge et al., [<reflink idref="bib31" id="ref50">31</reflink>]) 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. Previous studies have demonstrated that mean composite scores for Bayley III were slightly higher compared with composite scores for Bayley II. (Mebius et al., [<reflink idref="bib34" id="ref51">34</reflink>]) 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. (Gunn et al., [<reflink idref="bib13" id="ref52">13</reflink>], [<reflink idref="bib14" id="ref53">14</reflink>]; Andropoulos et al., [<reflink idref="bib1" id="ref54">1</reflink>]) Masoller et al. in a case-control stud demonstrated lower cognitive, language and motor. (Masoller et al., [<reflink idref="bib32" id="ref55">32</reflink>]) 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. (Andropoulos et al., [<reflink idref="bib2" id="ref56">2</reflink>])</p> <p>EEG background activity has been shown to be an important measure of functional brain maturation and impairment. (Lamblin et al., [<reflink idref="bib23" id="ref57">23</reflink>]) 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 correlating with lower cognitive and motor composite scores. This is consistent with findings of Gunn et al. demonstrating no association between preoperative aEEG background pattern and neurodevelopmental outcomes. (Gunn et al., [<reflink idref="bib13" id="ref58">13</reflink>]) Similarly, Robertson et al. showed no association between EEG abnormalities, reduced cerebral blood flow and neurodevelopmental outcomes. (Robertson et al., [<reflink idref="bib42" id="ref59">42</reflink>]) Severity of encephalopathy during the 24 h postoperative period was associated with poor language composite score on BSID-III (<emph>p</emph> = 0.026). Andropoulos et al. reported lower language scores associated with preoperative brain injury on MRI in infants with TGA who underwent cardiac surgery. (Andropoulos et al., [<reflink idref="bib1" id="ref60">1</reflink>]) Another study by William et al. demonstrated a positive correlation between preoperative left frontal polar and left frontal ß power and cognitive scores. (Williams et al., [<reflink idref="bib47" id="ref61">47</reflink>]) Hence, neonates with higher grades of encephalopathy and severity on EEG in the immediate 24 h postoperative period are at a higher risk of poor language scores on BSID-III.</p> <p>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 findings and used this data to classify EEG background based on severity of encephalopathy. However, this study has limitations too. This is a retrospective cohort study and included a small number of patients. The small number of participants did not allow for control of the severity and etiology of encephalopathy and future research is required to investigate this further. Only few neonates included in the study had brain MRI obtained in pre and post-operative period. 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 for associations between class of cardiac defects and cEEG findings and neurodevelopmental outcomes.</p> <hd id="AN0187434593-16">Conclusion</hd> <p>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 specifically associated with poor language composite scores. It is interesting to report a significant association between severity of encephalopathy during 24 h postoperative EEG monitoring with poorer language composite scores on BSID-III assessment. Early identification of high- risk infants is essential so that these infants would benefit from targeted early interventions to minimize neuromotor and behavioral deficits in the future. Further studies are needed to assess relationship between EEG background findings and neurodevelopmental outcomes in pre-school and school aged children with CHD.</p> <hd id="AN0187434593-17">Author Contributions</hd> <p>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. 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 stratification and statistical analysis. Dr. Aly, coordinated and supervised data collection, and critically reviewed the manuscript for important intellectual content.</p> <hd id="AN0187434593-18">Funding</hd> <p>The authors did not receive support from any organization for the submitted work.</p> <p>Open access funding provided by the Carolinas Consortium.</p> <hd id="AN0187434593-19">Declarations</hd> <p></p> <hd id="AN0187434593-20">Competing interests</hd> <p>The authors have no competing interests to declare that are relevant to the content of this article.</p> <hd id="AN0187434593-21">Publisher's Note</hd> <p>Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.</p> <ref id="AN0187434593-22"> <title> References </title> <blist> <bibl id="bib1" idref="ref33" type="bt">1</bibl> <bibtext> Andropoulos DB, Easley RB, Brady K, McKenzie ED, Heinle JS, Dickerson HA, Shekerdemian L, Meador M, Eisenman C, Hunter JV, Turcich M, Voigt RG, Fraser CD. 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  Data: Continuous Electroencephalogram (cEEG) Findings and Neurodevelopmental Outcomes in Neonates with Congenital Heart Disease (CHD) at 12-24 Months of Age
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  Data: <searchLink fieldCode="AR" term="%22Swetha+Padiyar%22">Swetha Padiyar</searchLink> (ORCID <externalLink term="http://orcid.org/0000-0002-7193-4631">0000-0002-7193-4631</externalLink>)<br /><searchLink fieldCode="AR" term="%22Neil+Friedman%22">Neil Friedman</searchLink><br /><searchLink fieldCode="AR" term="%22Elia+Pestana-Knight%22">Elia Pestana-Knight</searchLink><br /><searchLink fieldCode="AR" term="%22Linda+Franic%22">Linda Franic</searchLink><br /><searchLink fieldCode="AR" term="%22Sarah+Worley%22">Sarah Worley</searchLink><br /><searchLink fieldCode="AR" term="%22Hany+Aly%22">Hany Aly</searchLink>
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  Data: <searchLink fieldCode="DE" term="%22Brain%22">Brain</searchLink><br /><searchLink fieldCode="DE" term="%22Diagnostic+Tests%22">Diagnostic Tests</searchLink><br /><searchLink fieldCode="DE" term="%22Heart+Disorders%22">Heart Disorders</searchLink><br /><searchLink fieldCode="DE" term="%22Neurodevelopmental+Disorders%22">Neurodevelopmental Disorders</searchLink><br /><searchLink fieldCode="DE" term="%22Infants%22">Infants</searchLink><br /><searchLink fieldCode="DE" term="%22Toddlers%22">Toddlers</searchLink><br /><searchLink fieldCode="DE" term="%22Child+Development%22">Child Development</searchLink><br /><searchLink fieldCode="DE" term="%22Language+Skills%22">Language Skills</searchLink><br /><searchLink fieldCode="DE" term="%22Cognitive+Ability%22">Cognitive Ability</searchLink><br /><searchLink fieldCode="DE" term="%22Psychomotor+Skills%22">Psychomotor Skills</searchLink>
– Name: Subject
  Label: Geographic Terms
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22Ohio+%28Cleveland%29%22">Ohio (Cleveland)</searchLink>
– Name: SubjectThesaurus
  Label: Assessment and Survey Identifiers
  Group: Su
  Data: <searchLink fieldCode="SU" term="%22Bayley+Scales+of+Infant+and+Toddler+Development%22">Bayley Scales of Infant and Toddler Development</searchLink>
– Name: DOI
  Label: DOI
  Group: ID
  Data: 10.1007/s10803-024-06418-y
– Name: ISSN
  Label: ISSN
  Group: ISSN
  Data: 0162-3257<br />1573-3432
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Objective: This study aims to assess the role of continuous EEG (cEEG) background patterns and duration of cross-clamp time and cardiopulmonary bypass (CPB) in children with congenital heart disease (CHD) undergoing cardiac surgery and its correlation with abnormal neurodevelopmental outcomes at 12-24 months on Bayley Scales of Infant and Toddler Development (BSID-III). Methods: 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 significant 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.
– Name: AbstractInfo
  Label: Abstractor
  Group: Ab
  Data: As Provided
– Name: DateEntry
  Label: Entry Date
  Group: Date
  Data: 2025
– Name: AN
  Label: Accession Number
  Group: ID
  Data: EJ1481064
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=eric&AN=EJ1481064
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1007/s10803-024-06418-y
    Languages:
      – Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 12
        StartPage: 3245
    Subjects:
      – SubjectFull: Brain
        Type: general
      – SubjectFull: Diagnostic Tests
        Type: general
      – SubjectFull: Heart Disorders
        Type: general
      – SubjectFull: Neurodevelopmental Disorders
        Type: general
      – SubjectFull: Infants
        Type: general
      – SubjectFull: Toddlers
        Type: general
      – SubjectFull: Child Development
        Type: general
      – SubjectFull: Language Skills
        Type: general
      – SubjectFull: Cognitive Ability
        Type: general
      – SubjectFull: Psychomotor Skills
        Type: general
      – SubjectFull: Ohio (Cleveland)
        Type: general
      – SubjectFull: Bayley Scales of Infant and Toddler Development
        Type: general
    Titles:
      – TitleFull: Continuous Electroencephalogram (cEEG) Findings and Neurodevelopmental Outcomes in Neonates with Congenital Heart Disease (CHD) at 12-24 Months of Age
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Swetha Padiyar
      – PersonEntity:
          Name:
            NameFull: Neil Friedman
      – PersonEntity:
          Name:
            NameFull: Elia Pestana-Knight
      – PersonEntity:
          Name:
            NameFull: Linda Franic
      – PersonEntity:
          Name:
            NameFull: Sarah Worley
      – PersonEntity:
          Name:
            NameFull: Hany Aly
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      – BibEntity:
          Dates:
            – D: 01
              M: 09
              Type: published
              Y: 2025
          Identifiers:
            – Type: issn-print
              Value: 0162-3257
            – Type: issn-electronic
              Value: 1573-3432
          Numbering:
            – Type: volume
              Value: 55
            – Type: issue
              Value: 9
          Titles:
            – TitleFull: Journal of Autism and Developmental Disorders
              Type: main
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