Neurodevelopmental outcome related to cerebral risk factors in children after neonatal arterial switch operation

doi:10.1016/S0003-4975(00)02515-7

The Annals of Thoracic Surgery

Volume 71, Issue 3, March 2001, Pages 881-888

https://doi.org/10.1016/S0003-4975(00)02515-7 Get rights and content

Abstract

Background. Neurodevelopmental outcome after neonatal arterial switch operation for complete transposition of the great arteries is an important topic needing prospective assessment.

Methods. A group of 33 unselected children (3.0 to 4.6 years) operated on as neonates with combined deep hypothermic circulatory arrest and low flow cardiopulmonary bypass and a control group of 32 age-matched healthy children (3.0 to 4.8 years) underwent evaluation of socioeconomic and clinical neurological status and a standardized test comprising all areas of child development. Results of patients were related to those of the control group, to population norms, and to preoperative, perioperative, and postoperative cerebral risk factors.

Results. Clinical neurological status was normal in 26 patients (78.8%) and reduced in 7 (21.2%). Complete developmental score and the subscores for motor function, visual perception, learning and memory, cognitive function, language, and socioemotional functions were not different compared to population norms. Compared to the patients, the children of the control group scored higher on tests of complete development, cognition, and language, but also on socioeconomic status. Complete developmental score and the scores for motor, cognitive, and language functions were weakly inversely related to the duration of circulatory arrest, but not to the duration of bypass. Cerebral risk factors such as serum levels of the neuron-specific enolase, perinatal acidosis, perinatal asphyxia, peri- and postoperative cardiocirculatory insufficiency, or clinical seizures were not correlated to the test results.

Conclusions. Neonatal arterial switch operation with combined circulatory arrest and low flow bypass is associated with neurological impairment, but not with reduced development as assessed by formal testing of motor, cognitive, language, and behavioral functions. Perioperative serum level of the neuron-specific enolase is not a valid marker for later developmental impairment.

Section snippets

Patient population

Between January 1994 and December 1995, 45 full-term newborn infants with transposition of the great arteries underwent ASO. Total mortality was 2.2%: 1 patient with CHARGE-association died late postoperatively from cardiopulmonary insufficiency.

This prospective study was a case series with a control group as well as published control data and prognostic factor analyses. The study group comprised 33 unselected children (75% of the survivors). Participation in the study was determined mainly by

Neurological examination

Formalized clinical neurological scores were found normal in 26 patients (78.8%) and impaired in 7 (21.2%) as shown in Table 3. One of the latter patients had a well-functioning ventricular–peritoneal shunt because of perioperative intraventricular hemorrhage and permanent hydrocephalus, but no developmental abnormalities. Another patient suffered from mild left-sided hemiplegia and motor dysfunction, but not from further developmental impairment. Besides marked preoperative morbidity including

Comment

Data of the present prospective study are based on a homogeneous group of neonates with TGA in whom preoperative, perioperative, and postoperative care was conducted according to standardized protocols. Independent cerebral risk factors as well as dependent developmental follow-up data were prospectively evaluated in 75% of unselected surviving children. In addition, developmental examination of an age-matched control group of healthy children was performed. By means of univariable and

Acknowledgements

This study was supported by grants of “Bundesverband Herzkrankes Kind e.V.,” Germany. We thank Brigitte Gilles, PhD, Department of Psychology, Aachen University of Technology, Germany, for her valuable advice on analysis and interpretation of developmental testing. We express our gratitude to Jean Duchateau, MD, Department of Immunology, University Hospitals Brugman and St. Pierre, Free University Brussels, Belgium, for the determination of neuron-specific enolase in his laboratory.

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Congenital heart disease (CHD) affects roughly 40,000 children annually. Despite advancements, children undergoing surgery for CHD are at an increased risk for adverse neurological outcomes. At present, there is no gold standard for the diagnosis of cerebral injury during the perioperative period.
To determine the utility of brain injury biomarkers in children undergoing cardiac surgery.
We searched PUBMED, EMBASE, LILACS, EBSCO, ClinicalTrials.gov, Cochrane Databases, and OVID interface to search MEDLINE through July 2021 and assessed the literature following the snowball method. The search terms used were “congenital heart disease,” “cardiopulmonary bypass,” “biomarkers,” “diagnosis,” “prognosis,” and “children.” No language or publication date restrictions were used. Papers studying inflammatory and imaging biomarkers were excluded. The risk of bias, strengths, and limitations of the study were reported. Study was registered in PROSPERO ID: CRD42021258385.
A total of 1449 articles were retrieved, and 27 were included. Eight neurological biomarkers were examined. Outcomes assessed included prognosis of poor neurological outcome, mortality, readmission, and diagnosis of brain injury. Results from these studies support that significant perioperative elevations in brain injury biomarkers in cerebrospinal fluid and serum, including S100B, GFAP, NSE, and activin A, may be diagnostic of real-time brain injury and serve as an independent predictor of adverse neurological outcomes in patients with CHD undergoing cardiopulmonary bypass.
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Neurologic and psycho-intellectual outcome related to structural brain imaging in adolescents and young adults after neonatal arterial switch operation for transposition of the great arteries
2014, Journal of Thoracic and Cardiovascular Surgery
We studied brain structure abnormalities in adolescents and young adults who had undergone the neonatal arterial switch operation for transposition of the great arteries and related them to the neurologic and psycho-intellectual outcomes.
In a prospective longitudinal study, 60 unselected adolescents and young adults who had undergone surgery with combined deep hypothermic circulatory arrest and low flow cardiopulmonary bypass were re-evaluated at a mean age of 16.9 ± 1.7 years to determine their clinical neurologic status, intellectual development, and psychological condition. The results were related to population norms and anatomic structural abnormalities assessed by brain magnetic resonance imaging, with consideration of the risk factors in the preoperative and perioperative periods.
Neurologic impairment was more frequent (10%) than in the normal population. Although the average full-scale, verbal, and performance intelligence quotients were not reduced, scores >2 standard deviations less than the expected mean were increased. Above average scores were found for analytical thinking, but the orthography testing results were reduced. The self-rated psychological condition was better than expected. Magnetic resonance imaging demonstrated moderate or severe structural brain abnormalities in 32% of the patients. Periventricular leukomalacia was detected in >50%; its severity correlated with the grade of neurologic impairment, which correlated significantly with reduced intelligence, analytical thinking, and orthography. Preoperative acidosis and hypoxia were the only independent patient-related risk factors for neurologic dysfunction, reduced intelligence, periventricular leukomalacia, and reduced brain volume.
Despite encouraging overall neurodevelopmental outcomes, a significant minority had performances below the expected level, emphasizing the need for ongoing surveillance. Considering the high frequency of structural brain abnormalities, prospective long-term studies are needed to define their prognostic value with respect to the neuropsychological outcomes in childhood and adolescence.
Risk factors for neurodevelopmental impairments in school-age children after cardiac surgery with full-flow cardiopulmonary bypass
2012, Journal of Thoracic and Cardiovascular Surgery
To determine the risk factors for adverse neurodevelopmental outcomes in school-age children after full flow open-heart surgery for congenital heart disease.
The outcome was assessed in 117 children without a genetic comorbidity at a mean age of 10.4 ± 2.5 years. Intelligence was assessed using the Raven's Progressive Matrices and neuromotor function using the Zurich Neuromotor Assessment. Risk factors were retrieved from detailed chart review.
The mean intelligence score was 89 ± 16, significantly lower than the norm (P < .001). Cerebral palsy was diagnosed in 10% of patients. Poor neuromotor performance (less than p10) was present in 15% to 20% of the children, depending on the motor task (all P < .001). Pure motor and static balance performance was also significantly impaired when patients with cerebral palsy were excluded (P < .01). Intelligence was only related to socioeconomic status (P = .006), and neuromotor outcome was related to the length of hospital stay and postoperative neurologic abnormalities (P < .03). The extracorporeal circulation time was related to adaptive fine motor performance (P = .05). All other variables were not related to outcome.
Children without a genetic comorbidity are at risk of long-term intellectual and motor impairments also after full-flow cardiac repair. Surgery-related parameters play a less important role for adverse outcomes than postoperative complications. Our findings stress the importance of specialized follow-up assessments for all children with CHD undergoing open heart surgery.
Long-term outcome of speech and language in children after corrective surgery for cyanotic or acyanotic cardiac defects in infancy
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Citation Excerpt :
Children after cardiac operations for congenital heart defects with cardiopulmonary bypass (CPB) with or without hypothermic cardiac arrest generally are at risk of later neurodevelopmental impairment in the domains of motor functions, intelligence, academic achievement, attention, speech, language and behavior.1–15
The purpose of this prospective study was to assess whether outcome of speech and language in children 5–10 years after corrective surgery for tetralogy of Fallot (TOF) or ventricular septal defect (VSD) in infancy was influenced by the preoperative condition of hypoxemia or cardiac insufficiency and whether it was associated with perioperative risk factors and neurodevelopmental outcome.
A total of 35 unselected children, 19 with TOF and hypoxemia and 16 with VSD and cardiac insufficiency, operated with combined deep hypothermic circulatory arrest and low-flow cardiopulmonary bypass at mean age 0.7±0.3 (mean±standard deviation) years, underwent, at mean age 7.4±1.6 years, standardized evaluation of speech and language functions. Results were compared between subgroups and related to perioperative factors, sociodemographic and neurodevelopmental status.
Age at testing, socioeconomic status and history of speech and language development were not different between the subgroups. In contrast, total scores on oral and speech motor control functions (TFS) as well as on oral and speech apraxia (Mayo Test) were significantly reduced (p<0.02 to <0.05), and scores on anatomical oral structures tended to be lower (p<0.09) in the TOF group as compared to the VSD group. No differences were found for auditory word recognition and phonological awareness as assessed by the Auditory Closure subtest of the Illinois Test of Psycholinguistic Abilities and the test of auditory analysis skills, respectively. In all children, higher age at testing and better socioeconomic status were associated with better results in all domains of assessment (p<0.001 to <0.04). Consistent impairments of all oral and speech motor control functions (TFS and Mayo Test) were present in 29% of all children with a mean age of 6.5 years in contrast to 43% with normal performance and a mean age of 8.3 years. On the receptive speech tasks, only 6% scored below the normal range of their age group. TFS subscores were significantly correlated with age, bypass duration and motor function, but not correlated with socioeconomic status, duration of cardiac arrest, intelligence and academic achievement.
Children with preoperative hypoxemia due to cyanotic cardiac defects in infancy are at higher risk for dysfunction in speech and language than those with cardiac insufficiency due to acyanotic heart defects. Age at testing, socioeconomic status, and duration of cardiopulmonary bypass influenced test results. Long-term outcome in speech and language functions can be considered as a sensitive indicator of overall child development after cardiac surgery.
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2008, Brain and Development
To review reported neurodevelopmental outcome data for patients with congenital heart disease, identify risk factors for adverse neurodevelopmental sequelae and summarize potential neuromonitoring strategies that have been described. Methods: A Medline search was performed utilizing combinations of the keywords congenital heart, cardiac, neurologic, neurodevelopment, neuromonitoring, quality of life, and outcome. All prospective and longitudinal follow-up studies of patients with congenital heart disease were included. Additionally, studies that examined neuroimaging, neuromonitoring, and clinical factors in relation to outcome were examined. Case reports and editorials were excluded. Additional references were retrieved from selected articles if the abstract described an evaluation of neurodevelopmental outcomes and/or predictors of outcome in patients with congenital heart disease. Results: Overall, patients with CHD have increased rates of neurodevelopmental impairments, although intelligence appears to be in the normal range. Preoperative risk stratification, intraoperative techniques, postoperative care, and neuromonitoring strategies may all contribute to ultimate long-term neurodevelopmental outcomes in patients with CHD postsurgical repair. Conclusions: As advances in the medical and surgical management improves survival in patients with CHD, increasing knowledge about neurodevelopmental outcomes and the factors that affect them will provide for strategies to optimize long-term outcome in this high-risk population.
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Original article: cardiovascularNeurodevelopmental outcome related to cerebral risk factors in children after neonatal arterial switch operation

Abstract

Section snippets

Patient population

Neurological examination

Comment

Acknowledgements

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

J Pediatr

J Thorac Cardiovasc Surg

Ann Thorac Surg

J Cardiothorac Vasc Anaesth

J Thorac Cardiovasc Surg

Ann Thorac Surg

Electroenceph Clin Neurophys

J Cardiothorac Vasc Anaesth

J Cardiothorac Vasc Anaesth

Cognitive development of children following early repair of transposition of the great arteries using deep hypothermic circulatory arrest

Pediatrics

A comparison of the perioperative neurologic effects of hypothermic circulatory arrest versus low-flow cardiopulmonary bypass in infant heart surgery

N Engl J Med

Original article: cardiovascular
Neurodevelopmental outcome related to cerebral risk factors in children after neonatal arterial switch operation