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J Thorac Cardiovasc Surg 2008;136:1413-1421
© 2008 The American Association for Thoracic Surgery

Congenital Heart Disease

Five-year neurocognitive and health outcomes after the neonatal arterial switch operation

Ruth E. Neufeld, BSc, MCISc, MDa, Brenda G. Clark, MDa, Charlene M.T. Robertson, MDa,b,*, Diane M. Moddemann, MDc, Irina A. Dinu, PhDd, Ari R. Joffe, MDa, Reg S. Sauve, MD, MSce, Dianne E. Creighton, PhD, RPsyche, Lonnie Zwaigenbaum, MDa, David B. Ross, MDf, Ivan M. Rebeyka, MDa,f Western Canadian Complex Pediatric Therapies Follow-up Group*

a Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
b Pediatric Rehabilitation Outcomes Evaluation and Research, Glenrose Rehabilitation Hospital, Edmonton, Alberta, Canada
c Department of Pediatrics, University of Manitoba, Winnipeg, Manitoba, Canada
d School of Public Health, University of Alberta, Edmonton, Alberta, Canada
e Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada
f Department of Surgery, University of Alberta, Edmonton, Alberta, Canada

Received for publication January 8, 2008; revisions received March 28, 2008; accepted for publication May 4, 2008.

* Address for correspondence: Charlene M. T. Robertson, MD, Room 242, GlenEast, Glenrose Rehabilitation Hospital, 10230–111 Avenue, Edmonton, Alberta T5G 0B7, Canada. (Email: charlene.robertson{at}capitalhealth.ca).


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 Conclusions
 Table E1
 Table E2
 References
 
Objectives: We sought to assess the 5-year neurocognition and health of an interprovincial inception cohort undergoing the arterial switch operation for transposition of the great arteries.

Methods: Sixty-nine consecutive neonates had operations from 1996–2003 with full-flow cardiopulmonary bypass and selective deep hypothermic circulatory arrest. Outcomes were recorded at 58 ± 9 months of age. Univariate and multivariate analyses were used to identify outcome predictors, including surgical subtype and preoperative, operative, and postoperative variables.

Results: There was 1 (1.5%) operative death. Two children were lost to follow-up, and 1 was excluded because of postdischarge meningitis. Outcomes are reported for 65 survivors. Two (3%) children have cerebral palsy, and 7 (11%) have language disorders, 4 of whom also meet the criteria for autism spectrum disorder. Two of the 4 children with autism have an affected older sibling. Of the 61 children without autism, scores approach those of peers, with a full-scale intelligence quotient of 97 ± 16, a verbal intelligence quotient of 97 ± 18, a performance intelligence quotient of 96 ± 15, and a visual–motor integration score of 95 ± 16. Mother's education, birth gestation or weight, and postoperative plasma lactate values account for 21% to 32% of the variance of these scores. Septostomy adds 7% to the variance of visual–motor integration scores.

Conclusions: Most preschool children do well after surgical correction for transposition of the great arteries, including complex forms. Potentially modifiable variables include high preoperative plasma lactate levels and septostomy. A minority of children were given diagnoses of language disorders, including autism, in which familial factors likely contribute to outcome.

Abbreviations and Acronyms ASO = arterial switch operation; CPB = cardiopulmonary bypass; DHCA = deep hypothermic circulatory arrest; FSIQ = full-scale intelligence quotient; LD = language disorder; PIQ = performance intelligence quotient; TGA = transposition of the great arteries; VIQ = verbal intelligence quotient; VMI = Visual–Motor Integration–fourth edition; VSD = ventricular septal defect


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 Conclusions
 Table E1
 Table E2
 References
 
Neurodevelopmental outcome after surgical intervention for congenital heart disease is multifactorial, influenced by intrinsic characteristics of individual patients, and related to intraoperative and perioperative management and course.1,2Go Long-term follow-up of children who underwent the arterial switch operation (ASO) for correction of transposition of the great arteries (TGA) reveals small but important differences from general population normative data in cognitive function, motor skills, academic achievement, language ability, and behavior.3-10Go Some deficits become apparent only at school age, when the child is required to perform more complex cognitive, social, and linguistic skills that contribute to the development of peer relationships and literacy.11,12Go Results of a study at our institution demonstrated improved early motor outcomes in a cohort of children who had undergone the ASO compared with children from earlier surgical eras at other institutions.13Go In this article we describe the neurocognitive and health outcomes at 5 years of age for a subset of that cohort who underwent surgical intervention between 1996 and 2003.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 Conclusions
 Table E1
 Table E2
 References
 
This interprovincial inception cohort outcomes study enrolled 69 consecutive neonates undergoing the ASO for repair of TGA from September 1996 through May 2003 at Stollery Children's Hospital, Edmonton, Alberta, Canada. Based on the complexity of their cardiac anomalies, children were divided into 3 groups: group A, simple TGA with intact ventricular septum (n = 38); group B, TGA with ventricular septal defect (VSD; n = 20); and group C, complex TGA (n = 11). Additional anatomic diagnoses in group C included double-outlet right ventricle, single coronary artery, interrupted aortic arch, aortic coarctation or hypoplastic aortic arch, pulmonary artery anomaly, and left ventricle outflow tract obstruction or aortic stenosis. Two cardiac surgeons did the repairs. Operative procedures included predominantly full-flow (150 mL · kg–1 · min–1) cardiopulmonary bypass (CPB), with a target hematocrit value of greater than 0.25%, moderate hypothermia with selective use of deep hypothermic circulatory arrest (DHCA), and a modified pH-stat strategy used for cooling. The venous cannulation strategy varied throughout this period based on surgeon preference, with either a single venous cannula or bicaval cannulation used for simple TGA. Complex transpositions were repaired with bicaval cannulation. Intraoperative lactate measurements were not consistently done.

Prospectively collected predictor variables included patient and family demographics (sex, socioeconomic status,14Go maternal education, and year of operation), factors related to preoperative health status (antenatal diagnosis, use of balloon septostomy, ventilation time, age at operation, gestational age, and birth weight), preoperative and early and late postoperative measures of illness severity (highest dopamine level used, highest plasma lactate value, and lowest base deficit), operative variables (CPB time, lowest flow for >10 minutes on bypass, crossclamp time, DHCA time [if used], lowest temperature in degrees Celsius, and repeat CPB, if needed), and overall duration of ventilation, hospital days, presence of convulsions, or need for cardiopulmonary resuscitation, extracorporeal membrane oxygenation, or reintervention (see Table E1). The cohort was assessed at 6 to 10 months of age, 18 to 24 months of age (as previously reported13Go), and 4 to 6 years (range, 47.8–76.3 months) of age.

Outcome Assessment
Neurocognitive, neurologic, and health status outcomes were assessed at 58 ± 9 months of age by multidisciplinary neurodevelopmental teams at one of 5 centers in Western Canada: Calgary and Edmonton, Alberta; Regina and Saskatoon, Saskatchewan; and Winnipeg, Manitoba. History of hospitalizations, illnesses, medication use, and growth parameters, as well as family socioeconomic status14Go and maternal education (years of schooling), were recorded (Table 1 ). Physicians experienced in neurodevelopmental follow-up examined each child, as previously described.10,13Go Motor or sensory impairment was diagnosed if a child had cerebral palsy, visual impairment (corrected visual acuity in the better eye <20/60), or sensorineural hearing loss (responses >25 dB hearing level at any frequency from 250–4000 Hz). Hearing was evaluated by certified audiologists. Experienced pediatric psychologists or psychometrists assessed cognitive ability and visual–motor skills by using current age-appropriate standardized measures, including the Weschler Preschool and Primary Scales of Intelligence–third edition15Go and the Beery–Buktenica Developmental Test of Visual–Motor Integration–fourth edition (VMI; Table 2 ).16Go Variables included the United States normed full-scale intelligence quotient (FSIQ), verbal intelligence quotient (VIQ), performance intelligence quotient (PIQ), and VMI, each expressed as a standard score with a mean of 100 and standard deviation of 15.


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  		Table 1 Five-year health, growth, and development after the neonatal arterial switch operation in relation to the complexity of cardiac anomaly (n = 65)
 

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  		Table 2 Five-year psychologic test results in relation to type of cardiac lesion after the neonatal arterial switch operation
 
Speech and language concerns were identified by means of a 2-stage process. Children were assessed during cognitive evaluations, with further assessments completed by certified speech–language pathologists when concerns were identified. Speech disorders (articulation and phonologic), language delay (slower rate of language development but with typical sequence),17Go or language disorder (LD; deviation from typical rate and sequence of acquisition of specific language skill)17Go were diagnosed by speech–language pathologists based on clinical judgment informed by the results of standardized tests (Table 3 and see Table E2).


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  		Table 3 Characteristics of 7 normal-hearing preschool children after the neonatal arterial switch operation who had language disorders diagnosed clinically by speech–language pathologists
 
Children with LD were referred for further diagnostic assessment. Autism spectrum (hereafter autism) diagnoses were established based on structured clinical interview and behavioral observation (including the Autism Diagnostic Observation Schedule),18,19Go with clinical best diagnostic estimate based on the Diagnostic and Statistical Manual of Mental Disorders, fourth edition.20Go

Ethics board approval was obtained from each site, and all parents or guardians provided written informed consent. The funding agency has had no role in the data interpretation.

Statistics
One-way analysis of variance with Tamhane's post-hoc multiple comparisons, t tests, {chi}2 analysis, and Fisher's exact tests (all 2 sided) were used to compare groups; the Bonferonni correction was applied. Psychologic test results are given for the total group and for those without and with LD. In addition, predictions of outcome were determined separately for children without and with autism.

To screen for variables associated with psychologic scores, we used linear regression analysis. Multiple regression models consisted of variables found significant at a P value of .10 or less in the univariate analysis after screening for multicolinearity.

To screen for variables associated with autism, we used univariate logistic regression models. The final multiple logistic regression consisted of variables found significant at a P value of less than .10 in the univariate analysis after screening for multicolinearity.

Regression model results are reported as effect sizes (for psychologic scores) and odds ratios (for autism), along with confidence intervals and P values. Stepwise multiple regressions were used to explore the change in the percentage of variation in outcomes explained by each additional predictor to a significance level of .05.21Go Statistical analyses were performed with SAS version 9.1 (SAS Institute, Inc, Cary, NC).


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 Conclusions
 Table E1
 Table E2
 References
 
Description of Cohort
Of the 69 neonates, outcomes are reported for 65 children. One child with a complex lesion of the interrupted aortic arch, right ventricular outflow tract obstruction, and coronary artery anomalies died on postoperative day 22 after cardiopulmonary resuscitation and redo surgical intervention for right ventricular outflow tract obstruction. A second child was excluded because of problems unrelated to surgical treatment; this child had postdischarge bacterial meningitis with cerebral vasculitis and infarction, mild left lower extremity spastic monoplegia, low intelligence scores, and right profound sensorineural hearing loss. Preschool outcome information is not available for 2 children with operations within this time period; both were free of motor and sensory disability at 18 months of age.

Table E1 shows the background characteristics of the 65 five-year-old children after the neonatal ASO in relation to type of operation. Fewer neonates undergoing the ASO and VSD repair required any DHCA. Those undergoing complex repairs were more likely to require repeat CPB and longer crossclamp times.

Health, Growth, and Impairment Outcomes
Table 1 shows the health, growth, and impairment outcomes of these children at 5 years of age. The surgical subtype did not define outcomes. For one child, we confirm ambulatory cerebral palsy reported at 18 months.13Go That child had complex surgical intervention but without septostomy, a normal preoperative plasma lactate value, and a dural sinus thrombosis found on preoperative imaging. At 5 years of age, another child was given a diagnosis of mild left spastic hemiplegia. This second child had balloon septostomy, preoperative right middle cerebral artery infarction on brain imaging, and an increased preoperative plasma lactate value.

Neurocognitive Outcomes
Table 2 shows the psychologic scores for the entire cohort. There were no significant differences in relation to surgical subgroups, although scores for the ASO with VSD repair group are closest to normative values.

Further analyses of the 7 (11%) of 65 children (shown in Table 1) with LD was required. Psychologic scores of children with and without LD in relation to surgical subtype are shown in Table 2. For 58 children without LD, there were no differences in relation to surgical subtype. LD were found only in the children undergoing the ASO with and without VSD, with no difference between these 2 surgical subtypes.

Comparisons between the 58 children without LD and the 7 with LD were as follows: FSIQ—98 ± 16 (no LD) versus 76 ± 23 (LD), t = 2.444, P = .046; VIQ—98 ± 17 (no LD) versus 69 ± 19 (LD), t = 4.329, P < .001; PIQ—96 ± 15 (no LD) versus 85 ± 26 (LD), t = 1.079, P = .319; and VMI—94 ± 14 (no LD) versus 85 ± 31 (LD), t = 6.282, P = .415. Similarly, the proportion of scores less than 2 standard deviations (SDs) below the mean (IQ <70) was affected by children with LD as follows: FSIQ—1 (2%; no LD) versus 3 (43%; LD), sig = .003; VIQ—6 (10%; no LD) versus 3 (43%; LD), sig = .050; PIQ—3 (5%; no LD) versus 2 (29%; LD), sig = .086; and VMI—2 (3%; no LD) versus 2 (29%; LD), sig = .054.

Subgroup With LDs
Results of further assessment of the 7 children with LDs are reported in Table 3. All 7 children had a normal examination result at 7 to 10 months of age by a neurodevelopmental pediatrician, nurse, audiologist, and physical therapist. All 7 children had a multidisciplinary assessment at age 5 years, and all had normal hearing. Six of these 7 children were available for further assessment. Four (6.1%) children received a Diagnostic and Statistical Manual of Mental Disorders, fourth edition, diagnosis of autism by an expert multidisciplinary team consisting of a neurodevelopmental pediatrician, speech–language pathologist, and psychologist. Comparing psychologic tests for those 61 without autism and 4 with autism shows the following: FSIQ—97 (16; without autism) versus 67 (19; with autism), t = 3.706, P < .001; VIQ—97 (18; without autism) versus 64 (17; with autism), t = 3.722, P < .001; PIQ—96 (15; without autism) versus 75 (26; with autism), t = 2.721, P = .008; and VMI—95 (16; without autism) versus 76 (21; with autism), t = 2.410, P = .019.

Prediction of Outcomes for Children With and Without Autism
Data of 4 children with autism were removed before analysis of predictor variables for psychologic test results. For the 61 children without autism, Table 4 shows the variables from Table E1 associated with psychologic test results at a P value of .10 or less. After adjusting, few variables remain significantly related to the psychologic scores (Table 5 ). These remaining variables were sequentially entered into stepwise multiple regression analyses to show changes in the percentage of variance explained by each additional variable and the cumulative variances explained by the combination of these variables (Table 5). Of the variables in Table E1, only mother's education, gestational age, and day 1 highest plasma lactate value combine to explain intelligence scores. This latter variable, the only likely modifiable variable, explains less than 10% of the variance of these scores. The variables that combine to explain VMI scores are similar to those predicting the intelligence quotients but include septostomy, which explains an additional 7% of the variance, as well as birth weight instead of gestational age.


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  		Table 4 Significant (P < .10) variables found by means of linear regression analysis to be associated with 5-year psychologic test results after the neonatal arterial switch operation for the 61 children without autism spectrum disorder
 

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  		Table 5 Sequential stepwise multiple regression analysis of predictor variables * for each psychologic test for the 61 five-year-old children without autism spectrum disorder after the neonatal arterial switch operation
 
The variable DHCA was not included in Table 4 because the duration of DHCA did not reach a significant level of unadjusted effect size on univariate analysis. However, all 5 of the children with PIQ scores of less than 70 had DHCA. Of the 33 children requiring DHCA, 5 (15%) had PIQ scores of less than 70 compared with no PIQ scores of less than 70 for those 32 children without DHCA (exact sig = .053).

Children With Autism
All variables from Table E1 were compared for the children with and without autism. Differences were found only in preoperative highest plasma lactate values (7 [6] mmol/L [with autism] vs 4 [7] mmol/L [without autism], t = –2.215, P = .03) and DHCA time (n = 33; 7 [3] minutes [with autism] vs 19 [20] minutes [without autism], t = 2.945, P = .006). All 4 children with autism had intact ventricular septum and the ASO, resulting in a prevalence of 11% in this subgroup. Three of the 4 children with autism had septostomy, and 2 of these required DHCA. The fourth child had DHCA without septostomy. None of the 4 with autism had an antenatal diagnosis of TGA; required repeat CPB in the operating room, extracorporeal membrane oxygenation, cardiopulmonary resuscitation, or reintervention; or had convulsions. Two children with autism and 1 child with an LD without autism have a sibling with Asperger's syndrome. A retrospective review of charts revealed no other child had a sibling with autism. Genetic investigations were negative for karyotype, Fragile X, del 22q.11.2 in 4 children with autism and also for Rett syndrome in 1 girl. Three children with autism had a normal magnetic resonance image on hospital discharge, and 1 had a small subependymal hemorrhage; this latter child and one of the other children with autism had repeated normal magnetic resonance image results.

We assessed whether any variables were predictive for autism. The only variables significantly related to autism at a P value of less than .10 in univariate logistic regression analysis were having a sibling with autism and highest preoperative plasma lactate value. In the multiple logistic regression model the odds for autism were 7.18 times higher for patients having a sibling diagnosed with autism (odds ratio, 7.18; confidence interval, 3.71–1389.41; P = .005). After adjusting for children having a sibling with autism, the odds ratio of autism corresponding to the highest preoperative plasma lactate value was 1.27 (confidence interval, 0.99–1.61), with marginal significance (P = .057).


   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
Conclusions
 Table E1
 Table E2
 References
 
This article confirms the low mortality previously reported13,22Go and adds to previous publications3,6Go on the preschool outcomes after the ASO by presenting data from a later surgical era. In keeping with past publications,3,13Go children with diagnoses such as postdischarge meningitis and autism considered to be unrelated to the perioperative period were excluded from predictive analysis. The finding that 4 (6%) of the 65 children in the cohort had autism is unusual.

This article suggests that after the ASO for TGA, children at 5 of years of age are similar to their peers in terms of growth and health parameters, with few exceptions. Two (3%) of 65 children had motor impairment linked to preoperative complications, and 17 (26%) children had speech difficulties, language difficulties, or both. Seven (11%) of 65 children had LD. Cognitive ability for the total cohort, and more specifically for those without LD, compares favorably with the published literature.3,6,9,10Go Those with LD differed significantly from those without LD on their FSIQ and VIQ measurements, which is in keeping with their diagnosis. They demonstrated relative strength but with wide variability in nonverbal areas. Four of the 7 children with LD were given diagnoses of autism characterized by deficits in social interaction, impaired communication, and restricted or repetitive interests and behaviours.20Go These children differed significantly from the remainder of the cohort on all psychologic measures, including the nonverbal measures.

Stepwise multiple regression analyses of the 5-year psychologic scores for children without autism show that less than one third of the variance within the scores can be explained by the studied variables. Mother's education is a predictor. Low birth weight is also related to outcomes, which is consistent with other reports.22Go The highest plasma lactate value within the first postoperative day explains 6% to 10% of the variance in intelligence scores and supports previous findings.23Go Because this is a potentially modifiable variable, further investigation into causes of high lactate values could lead to improved outcomes. Similar to the prediction of intelligence scores, only 26% of the variation in VMI scores was explained by the studied variables; the use of septostomy contributed 7% and was associated with lower scores. There is potential for improvement with further study of brain insult associated with septostomy24Go or the underlying hypoxia contributing to its use.

This study found a high percentage of children with speech and language difficulties. Children who have undergone the ASO for TGA have been reported to have significantly greater language difficulties compared with the general population, despite cognitive abilities in the average range.3,4,6,8,9Go Although structural aspects of language (vocabulary and syntax) appear intact, specific difficulties with symbolic talk during play and storytelling, particularly with describing the story character's internal affective states, are at risk.11,12Go

We found an unexpectedly high rate of autism in our sample of children undergoing the ASO, roughly 10 times higher than current prevalence estimates of 6 per 1000.25Go Diagnosable medical conditions, syndromes, and single-gene disorders make up less than 10% of autism diagnoses.25,26Go Evidence from family and twin studies suggests that "idiopathic" autism is highly inheritable because of interactions of multiple genes modified by epigenetic and environmental factors.26Go In this study 2 of the 4 children with autism had an older sibling with Asperger's syndrome. Hence the increased rate of autism in our cohort might partly be related to overrepresentation of related disorders among siblings. In addition, 1 of the 3 children with LD had a sibling with autism.

Several studies have investigated prenatal and perinatal risk factors associated with autism.27,28Go High preoperative plasma lactate values, a surrogate measure of tissue hypoperfusion, was the only medical variable that was more abnormal among children with autism in this study. This variable had marginal predictive significance in multivariate analysis. However, all 4 children with autism had TGA with an intact ventricular septum, a group at risk for increased hypoxia. The septostomy received by 3 of the 4 children with autism is also linked to preoperative brain injury.24Go Specific brain injury is not supported for these children because brain imaging was within normal limits. In children with TGA, abnormal fetal circulation and brain oxygenation, neonatal hypoxia, and surgical risks are well known.29Go Abnormal brain microstructure and metabolism have been reported in newborns with congential heart disease.30Go Any of these insults can interact with a genetic predispostion to lead to autism. TGA is generally considered an isolated cardiac malformation that is rarely associated with genetic syndromes. However, should the association of TGA and autism in this article be confirmed, this might indicate a shared genetic susceptibility or shared environmental insult during development.

The strengths of this study are the high proportion of children, 95.5% of survivors, available at 5 years for individual assessment and the prospectively collected predictive variables. Although follow-up occurred at 5 centers, all assessors were certified, protocols were closely followed, and the centers have worked as a multisite research team since 1996. A limitation of this article is the small number of subjects with complex forms of TGA; however, some studies do not include these children,3,4Go and this study provides an opportunity to view their outcomes. The major limitation of the study is that not all children were seen by a speech–language pathologist, and thus the speech and language diagnoses might underestimate the proportion of children with these difficulties. Also, not all parents were asked about a family history of autism, although all were asked whether there were child development or mental health concerns in the extended family. No comparison subjects are available for this study, but standardized measures with population-normative data are used throughout.


   Conclusions
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusions
Table E1
 Table E2
 References
 
After the ASO, preschool children have cognitive skills within population norms. However, we report an increased incidence of LD, supporting concern about discourse abilities. Follow-up of children after the neonatal ASO should include a complete speech and language evaluation, with particular attention to social use of language and family history of LD, autism, or both. Investigation into a possible genetic link between TGA and autism is recommended. The importance of mother's schooling as a predictor of psychologic test results, the link of TGA with autism, and the minimal effect of intraoperative variables on cognitive scores support a strong genetic influence in the outcome of these children.


   Table E1
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusions
 Table E1
Table E2
 References
 

Characteristics of 65 survivors undergoing the neonatal arterial switch operation in relation to complexity of cardiac anomaly
Total (n = 65) ASO (n = 36) ASO/VSD (n = 19) Complex (n = 10) F or {chi}2 P value *
Preoperative
 Socioeconomic status {dagger} 42 (12) 42 (14) 44 (10) 42 (12) 0.264 .769
 Mother's schooling (y) 13 (3) 13 (3) 13 (5) 12 (2) 0.224 .800
 Male sex 42 (65%) 23 (55%) 13 (31%) 6 (14%) 0.222 .895
 Year of operation 1999.9 (2.0) 1999.5 (2.1) 2000.8 (1.7) 1999.5 (1.8) 3.106 .052
 Antenatal diagnosis 6 (9%) 2 (6%) 4 (21%) 0 (0%) 4.766 .092
 Age at operation (d) 11 (7) 10 (7) 10 (8) 14 (7) 1.336 .270
 Birth gestation (wk) 39 (2) 39 (2) 39 (1) 38 (3) 0.972 .384
 Birth weight (kg) 3.4 (0.6) 3.3 (0.5) 3.4 (0.5) 3.5 (1.0) 0.128 .880
 Balloon septostomy 35 (54%) 24 (68%) 8 (42%) 3 (30%) 5.723 .057
 Ventilation (d) 5 (4) 4 (4) 4 (3) 6 (8) 1.103 .338
 Highest dopamine used (µg · kg–1 · min–1) 4.4 (7.2) 5.9 (8.2) 3.4 (5.9) 1.1 (3.2) 2.183 .121
 Highest plasma lactate value (mmol/L) 3.6 (3.3) 4.0 (3.8) 3.5 (2.7) 2.0 (1.4) 1.610 .208
 Lowest base deficit (mmol/L) –4.4 (4.7) –5.6 (4.3) –4.1 (3.9) –0.3 (5.6) 5.744 .005
Operative
 Cardiopulmonary bypass time (min) 137 (74) 123 (75) 136 (21) 190 (113) 3.463 .038
 Lowest flow for >10 min (mL · kg–1 · min–1) 104 (30) 105 (34) 107 (29) 95 (14) 0.604 .550
 Crossclamp time (min) 68 (22) 57 (16) {ddagger} § 74 (12) 96 (26) 21.979 <.001
 Lowest temperature during CPB (°C) 25 (3); range, 19–29 25 (3) {ddagger} 26 (2) {ddagger} 23 (3) 4.855 .011
 DHCA used 33 (50%) 27 (75%) 2 (11%) 4 (40%) 21.232 <.001
 DHCA time (min; n = 33) 18 (19) 16 (18) 15 (10) 37 (24) 2.315 .116
 Lowest temperature just before DHCA (°C) 23 (2); range, 19–27 23 (2) 21 (0.4) 22 (3) 1.059 .359
 Need for re-CPB 7 (11%) 1 (3%) 1 (5%) 5 (50%) 19.008 <.001
Postoperative, <24 h
 Highest dopamine used (µg · kg–1 · min–1) 7.6 (4.7) 7.5 (3.8) 8.0 (5.8) 7.1 (5.8) 0.106 .900
 Highest plasma lactate (mmol/L) 5.3 (2.6) 5.5 (2.3) 5.1 (3.0) 5.0 (2.6) 0.246 .783
 Lowest base deficit (mmol/L) 0.88 (3.2) 1.7 (3.2) § –1.0 (2.4) 1.5 (3.6) 5.093 .009
Postoperative >24 h
 Highest dopamine dosage used (µg · kg–1 · min–1) 7.1 (4.9) 7.4 (4.6) 6.4 (5.6) 7.6 (4.7) 0.293 .747
 Highest plasma lactate value (mmol/L) 2.1 (0.9) 1.9 (0.8) 2.5 (1.2) 2.1 (0.7) 2.143 .126
 Lowest base deficit (mmol/L) 1.4 (3.3) 2.1 (3.4) 0.1 (2.4) 1.6 (3.9) 2.187 .121
Overall
 Duration of ventilation (d) 9 (10) 8 (12) 9 (9) 11 (7) 0.378 .686
 Duration of hospitalization (d) 27 (25) 27 (26) 26 (26) 29 (17) 0.065 .937
 Clinical convulsions occurred 4 (6%) 3 (8%) 1 (5%) 0 (0%) 0.978 .613
 Cardiopulmonary resuscitation required 2 (3%) 0 (0%) 0 (0%) 2 (20%) 11.349 .003
 Extracorporeal membrane oxygenation used 2 (3%) 1 (3%) 0 (0%) 1 (10%) 2.221 .329
 Reintervention 6 (9%) 1 (3%) 2 (11%) 3 (30%) 6.976 .031
* One-way analysis of variance or {chi}2 analysis.
{dagger} Mean (SD) = 43 (13); Blishen and colleagues.14Go
{ddagger} Significant difference from the complex group (P < .01).
§ Significant difference from the ASO/VSD group (P < .01).

Values are presented as means (standard deviations) or number (percentage). Note: After the Bonferonni correction, P values of .001 or less remain significant. ASO, Isolated arterial switch operation; ASO/VSD, ASO with ventricular septal defect repair; CPB, cardiopulmonary bypass; DHCA, deep hypothermic circulatory arrest.


   Table E2
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusions
 Table E1
 Table E2
References
 

References for language measures
CARS Schopler E, Reichler RJ, Renner BR. The Childhood Autism Rating Scale. Los Angeles, Calif: Western Psychological Services; 1988.
CELF3 or 4 Semel EM, Wiig EH, Secord W. Clinical Evaluation of Language Fundamentals–third edition. San Antonio, Tex: The Psychological Corporation; 1995.
 Semel EM, Wiig EH, Secord W. Clinical Evaluation of Language Fundamentals–fourth edition. San Antonio, Tex: The Psychological Corporation; 2003.
CSBS Wetherby AM, Prizant BM. Communication and Symbolic Behaviour Scales Developmental Profile: first normed edition. Baltimore, Md: Brookes Publishing Co; 2002.
GADS Gilliam JE. Gilliam Asperger's Disorder Scale. Austin, Tex: PRO-ED; 2001.
PPVT–III Dunn LM, Dunn LM. Peabody Picture Vocabulary Test, third edition. Bloomington, Minn: Pearson; 1997.
PLAI–II Blank M, Rose SA, Berlin LJ. Preschool Language Assessment Instrument, second edition. Austin, Tex: Pro-Ed; 2003.
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   Acknowledgments
 
We thank the families of these children for their active participation in the developmental sites across western Canada and their commitment to this project. We sincerely thank the research and data coordinators and psychologists who made this research study possible: H. Christianson and D. Anseeuw-Deeks, Calgary, Alberta, Canada; K. Penner, J. Bow, and V. Debooy, Winnipeg, Manitoba, Canada; B. Acton, Saskatoon, Saskatchewan, Canada; S. Selzer and H. Switzer, Regina, Saskatchewan, Canada; and Jill Tomlinson, G. Alton, and W. Biggs, Edmonton, Alberta, Canada.


   Footnotes
 
Supported initially by the Glenrose Rehabilitation Hospital Research Trust Fund with ongoing support from the Registry and Follow-up of Complex Pediatric Therapies Project, Alberta Health and Wellness.

No reprints will be available from the authors.

* P. Blakely, Saskatoon, Saskatchewan, Canada; A. Ninan, Regina, Saskatchewan, Canada. Back


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusions
 Table E1
 Table E2
 References
 

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