One hundred and three term infants who underwent surgery for CHD before 3 months of age between January 2013 and February 2016 at the NICU in our hospital were included in the study. Those infants who had any form of genetic or chromosomal abnormality independently associated with impaired neurodevelopment or were born before 37 weeks of gestational ages were excluded. The study was approved by the Ethics Committee of Guangdong General hospital, and written informed consent was obtained from all the parents.

Clinical data including Apgar scores, gestational age, birth weight, blood gas analysis, cardiovascular function, respiratory and multiorgan failure, neurological examination results, seizure occurrence, drug administration, neuroimaging data, infection, and surgical records were evaluated retrospectively for the study. Specifically, infection included postoperative sepsis diagnosed as bacterial infection by blood culture, and severe post-operative infection defined as postoperative infection (mainly pulmonary and urinary tract infections but not intracranial infection) that required antibiotics treatment, while excluding sepsis. Surgical procedures, cardiopulmonary bypass (CPB) time, and aortic cross-clamping (ACC) time were obtained from the surgical records.

aEEG was monitored 1 or 2 days before cardiac surgery and 3 or 7 days after surgery using an 8-channel EEG acquisition system (Nicolet One Monitor, Care Fusion, San Diego, California). The period of aEEG monitoring lasted for at least 24 hours each time and was extended when necessary. Eight disposable, self-adhesive EEG scalp electrodes (Blue Sensor BRS-50 K Ambu ECG electrode; Medicotest A/S, Ølstykke, Denmark) were applied in a reduced montage following the international 10-20 system. The 8-channel cross-brain aEEG trace was derived and displayed at 6 cm/hour on paper using a semi-logarithmic scale to assess and classify the aEEG background pattern. The channels were also used to record EEG data to describe episodes of EEG seizures in 10-second epochs. The 8-channel EEG recording was examined for the entire recording period when necessary. To ensure masking of evaluator, the expert who performed the main offline aEEG analyses was not involved in the clinical care of the infants.

A total of 103 infants with CHD undergoing cardiac surgery were evaluated for the study. Demographic and clinical characteristics of all patients are shown in Table I. The mean (SD) gestational age at birth was 38.6 (2.4) weeks, while the mean age at surgery was 1.4 (1.2) months. The infants were classified into four types as previously defined, among which two-ventricle heart without arch obstruction was the predominant group (76, 73.8%), both two-ventricle heart with arch obstruction and single-ventricle heart without arch obstruction groups accounted for 12.6% of the total cases (n=13), and only one infant developed single-ventricle heart with arch obstruction. The comparison of pre- and postoperative aEEG results suggested that the background pattern was improved significantly after surgery (P=0.04) in infants of no more than 39 gestational weeks. The similar trends were observed for the SWC and seizure activity after surgery, but the differences were not statistically significant (Table II). Since background patterns of only five infants turned worse after surgery, the changes in background pattern were classified as improved and not improved (including not changed and worse). Multivariate logistic regression analysis suggested that gestational age was the only factor affecting postoperative background pattern improvement (OR=0.20, 95% CI: 0.04-0.97; P=0.04), whereas bodyweight was not significant predictor for the improvement (Table III). Infants with postoperative sepsis or severe postoperative infection were more likely to show a worsened SWC after heart surgery (OR=0.12, 95% CI: 0.02-0.67, P=0.02 and OR=6.77, 95% CI:1.60-28.68, P=0.01, respectively).

TABLE I Demographic and Clinical Characteristics of the Study Population (N = 103)

TABLE II Changes between Pre- and Postoperative aEEG (N=103)

TABLE III Logistic Regression Analysis for Influencing Factors of Changes of Background Pattern and SWC

In the present study, background pattern of aEEG was improved in some infants after cardiac surgery, and the improvement was more likely to be identified in those with gestational age less than 39 weeks. Individuals with postoperative sepsis or severe infection were at increased risk of getting worse SWC after the operation. Our results demonstrate that gestational age and postoperative infection are predictive of benefits or harm after the surgery in terms of brain function.

Heart surgery may improve brain function of infants with CHD, as is indicated by the improvement of background pattern in some individuals. Several studies have demonstrated that normal background pattern of aEEG was observed in most infants preoperatively [11,12], which was in line with our study. However, few studies have reported the improvement of background pattern after surgery. In fact, the occurrence of abnormal background pattern was increased after surgery in one study [13]. The differences should be interpreted with caution as the time for conducting aEEG monitoring was different and the sample size of both studies is relatively small.

We did not perform intra-operative aEEG monitoring in the study due to the unstable quality and lack of predictive value. Gunn K, et al. [14] found that aEEG background pattern will recover to the normal in most cases and there was considerable variability in the intraoperative pattern. Furthermore, postoperative but not intraoperative aEEG proved effective in identifying cerebral injury in infants with CHD [15].

Our study identified two factors that may help infer which individual would gain benefits or harm regarding brain function from cardiac surgery. Multiple risk factors, of preoperative, intraoperative, or postoperative, have been identified. Petit, et al. [16] reported that preoperative low arterial hemoglobin saturation was associated with transposition of the great arteries [16]. Cardiac arrest before surgery was found to increase risk of developing brain injury [6]. Prolonged total circulatory arrest during the operation was reported to be related to white matter brain injury [17]. Another study suggested that single ventricle physiology after the surgery was likely to increase risk of brain injury [18]. Our research focused on the changes of aEEG patterns and pinpointed two novel variables, namely gestational age and postoperative infection, as influencing factors for brain function, which may provide valuable insights for clinical practices.

Our study had several limitations. Most importantly, the retrospective character limits the level of evidence. Sample size was small, which requires further validation of the findings. We did not systematically record intraoperative anesthetic use or report the effects of these drugs on outcomes. Lastly, long-term neurodevelop-mental outcomes were not investigated.

In conclusion, we retrospectively correlated clinical factors with brain function measured by aEEG, highlighting gestational age and postoperative infection as predictors for improvement of cerebral function. If this is confirmed in larger prospective studies, it would help optimize and personalize the perioperative procedures for CHD to achieve better neurodevelopmental outcome.

Contributors: JG: study design and manuscript preparation; SRH, JZ, JMC: guarantor of integrity of the entire study; YXS: study concepts; YML,SXL: clinical studies; CC: statistical analysis; YR: data acquisition; BW: data analysis. All authors are approved to this manuscript.

Funding: This work was supported by the National Key Research and Development Plan Project (2018YFC1002600).

Competing Interest: None stated.

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