Cardiology in the Young (2015), 25, 903–910
© Cambridge University Press, 2014
doi:10.1017/S1047951114001140
Original Article Neurodevelopmental outcome following open heart surgery in infancy: 6-year follow-up Bryn Jones,1,2 Frank Muscara,3 Owen Lloyd,4 Lynne McKinlay,4 Robert Justo5 1
Department of Cardiology, The Royal Children’s Hospital, Melbourne; 2Department of Paediatrics, University of Melbourne; 3Murdoch Children’s Research Institute, Melbourne; 4Queensland Paediatric Rehabilitation Service, Royal Children’s Hospital, Brisbane; 5Queensland Paediatric Cardiac Service, Mater Health Services, Brisbane, Australia Abstract Background: Children undergoing open heart surgery are at risk of neurological injury. A cohort of 35 patients, who had undergone cardiac surgery during infancy, had a significant reduction in Bayley Scale of Infant Development scores at a 12-month assessment. This cohort has now reached an appropriate age to reassess developmental progress. Methods: Detailed psychometric testing was conducted on 20 children from the original cohort using the Weschler Preschool and Primary Scale of Intelligence, the Wide Range Assessment of Memory and Learning, and the Wechsler Individual Achievement Test. Parents completed the Connor’s Rating Scale, the Behaviour Rating Scale of Executive Functioning, and the Child Behaviour Checklist. Results: The mean age of the cohort at assessment was 6.6 (standard deviation 0.4) years. Mean scores on all tests of intelligence, memory, academic achievement, and executive function fell within the average range. Of the children, 20–35% were found to have significant difficulties across these areas. Mean scores in the areas of social, emotional, behavioural, and psychological functioning also fell within the average range. Of the children studied, 35% had clinically significant problems in these areas. There was only a weak association between the 12-month scores and the FullScale Intelligence Quotient at 6 years. Conclusion: Detailed psychometric testing of these children suggests that they generally function in the average range; however, a significant proportion falls below age expectations in all the areas assessed. This highlights the importance of long-term follow-up with routine developmental screening to allow identification of a subgroup that may benefit from early educational and behavioural intervention. Keywords: Heart defects; congenital; paediatric cardiac surgery; developmental outcome Received: 16 April 2014; Accepted: 10 June 2014; First published online: 10 July 2014
C
HILDREN BORN WITH CONGENITAL HEART DISEASE
(CHD) now have an increased chance of longterm survival thanks to advances in surgical techniques.1 Despite these improvements, children undergoing cardiac surgery procedures with cardiopulmonary bypass remain at risk for neurological injury.2,3 Studies have shown that a small percentage (2.3–5.9%) of the patients have acute perioperative events, ranging from transient seizure with no long-term Correspondence to: Dr B. Jones, Department of Cardiology, The Royal Children’s Hospital, Flemington Road, Parkville, Melbourne, Victoria 3052, Australia. Tel: + 61 3 93455713; Fax: + 61 3 93456001. E-mail: [email protected]
sequelae to permanent and severe neurological disabilities.4–7 However, a significantly larger proportion is at risk of longer-term educational and behavioural difficulties, with a pattern of neurodevelopmental problems similar to that seen with preterm infants.8–10 Although it is well established that children with CHD are at risk of longer-term educational and behavioural difficulties, these are often not identified until the child reaches school age, and predictors of these outcomes have not been well established. A previous study conducted by our group11 prospectively examined a cohort of infants who underwent cardiac surgery with cardiopulmonary bypass between
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1999 and 2001. A total of 47 infants were enrolled before cardiac surgery and underwent detailed preoperative neurodevelopmental assessment and postoperative monitoring, with 35 of them undergoing follow-up neurodevelopmental assessment at 1 year. The primary aim was to assess the power of perioperative markers associated with neurological injury – electroencephalographic abnormalities, reduced cerebral arterial blood flow velocity, and elevated serum S-100B levels – to predict neurological outcomes at 1 year of age. At 1-year follow-up, there were lower neurodevelopmental scores compared with the preoperative assessments (mean mental scores changing from 103 ± 5 to 04 ± 13 (p = 0.001), and mean motor scores changing from 99 ± 8 to 89 ± 20 (p = 0.004)). However, no association was found between electroencephalographic abnormalities, reduced cerebral arterial blood flow velocity or elevated serum S-100B levels, and impaired neurodevelopmental outcome. This aim of the current study was to assess the neurodevelopmental status of this cohort of children 6 years following their surgery as infants. Specifically, outcomes of interest included current level of cognitive functioning or intelligence, memory and learning skills, level of academic achievement, and executive function, as well as behavioural and psychological functioning. A secondary aim was to determine whether there was any correlation between perioperative risk factors, previous developmental factors, and current level of functioning.
Materials and methods Participants The study is a prospective cohort study and involved the long-term follow-up of a previously assessed cohort 6 years following cardiac surgery. Parents of participants who had been enrolled in the previous study were contacted and their children invited to participate in the follow-up study. The initial study involved 47 infants with structural heart disease aged 16 days–4 months, admitted for cardiac surgery requiring cardiopulmonary bypass at the Prince Charles Hospital, Brisbane, Australia. Exclusion criteria were: known chromosomal abnormalities, associated extracardiac malformations, or an abnormal neurological examination. Of the 47 infants, 35 children had been followed up to 12 months of age. Procedure At study commencement, data were obtained on demographic – age, weight, gestational age – anatomical, and surgical details – cardiac diagnosis, surgical details, requirement for further surgery. In addition, neurodevelopmental data were collated from the first study.
June 2015
All participating children underwent a detailed psychometric assessment performed by two trained neuropsychologists. Parents were asked to complete the questionnaires while their child was being assessed. Family socio-economic status was also assessed with parental questionnaires.
Measures Cognitive function. The Wechsler Primary and Preschool Scale of Intelligence – third edition12 was used to assess intellectual abilities, which in addition to Full-Scale Intelligence Quotient assesses verbal and non-verbal cognitive functioning and speed of information processing. Outcome measures included Full-Scale Intelligence Quotient, Verbal Intelligence Quotient, Performance Intelligence Quotient, and the Processing Speed Quotient (Mean = 100, standard deviation = 15). Memory and learning. Wide Range Assessment of Memory and Learning – second edition13 was used to assess verbal and visual memory and learning, and the recognition of the same information. Outcome measures included a General Memory composite, and a General Recognition Composite (Mean = 100, standard deviation = 15). Academic achievement. The Abbreviated Wechsler Individual Achievement Test – second edition14 was used as a screen of literacy and numeracy functioning. Scores from the spelling, word reading, and numerical operations subtests were used as outcome measures (Mean = 100, standard deviation = 15). Executive function. The Behaviour Rating Inventory of Executive Function–Parent Version15 was used to obtain parent ratings of current functional and behavioural aspects of executive function. The General Executive Composite Score (Mean = 50, standard deviation = 10) was used as an outcome measure or executive function. A higher score indicates a higher level of executive dysfunction, with a score of 65 or above, indicating abnormal elevation. Behavioural functioning. The Child Behaviour Checklist16 assessed parental perceptions of the child’s emotional, social, and behavioural functioning. The Internalising Problems Score, Externalising Problems Score, and the Total Problems Score (Mean = 50, standard deviation = 10) were used as outcome measures. Higher scores indicate greater behavioural problems, with scores between 65 and 69 in the borderline clinical range, and scores of 70 and above in the clinical range. Psychopathology. The Conner’s Parent Rating Scale–Revised17 was also used to assess child psychopathology, with respect to clinical diagnoses of attention disorders. The Diagnostic and Statistical Manual of Mental Disorders-IV Total Score, the
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Table 1. Comparison of cardiac diagnosis between original cohort and follow-up group.
Cardiac diagnosis
Original cohort number enrolled (n = 35)
Follow-up group number enrolled (n = 20)
Transposition of the great arteries Tetralogy of Fallot Ventricular septal defect Total anomalous pulmonary venous drainage Common arterial trunk Complex functionally single ventricle
12 9 8 2 2 2
9 5 4 1 1 0
Table 2. Comparison of intraoperative details between original cohort and follow-up group
Age at repair (days) [mean (SD)] Weight at repair (kg) [mean (SD)] Bypass time (minutes) [mean (SD)] Circulatory arrest [n (%)] Circulatory arrest time (minutes) [mean (SD)]
Original cohort (n = 35)
Follow-up group (n = 20)
p-value
57 (15) 4.3 (3.4) 147 (74) 8 (23%) 12 (3)
52 (43) 4.3 (0.9) 155 (55) 5 (25%) 16 (8)
0.53* 1* 0.67* 0.01*
*Paired t-test
Diagnostic and Statistical Manual of Mental Disorders-IV Attention-Deficit Hyperactivity Disorder Inattentive Score, and the Diagnostic and Statistical Manual of Mental Disorders-IV Attention-Deficit Hyperactivity Disorder hyperactive/impulsive Score (Mean = 50, standard deviation = 10) were outcome measures. A higher score indicates greater concern regarding these areas of functioning, with scores of 60–69 considered elevated, and scores above 70 considered highly elevated. The study was approved by the Prince Charles Hospital Human Research Ethics Committee and informed consent was obtained in all cases.
Statistical analysis All statistical tests were conducted using GraphPad Prism version 3.02 for Windows (GraphPad Software, San Diego, United States of America. http:// www.graphpad.com). Values are expressed as mean (standard deviation) or number (%) as appropriate. For comparative data, two-tailed paired t-tests were used. Spearman’s correlation coefficients, with twotailed hypothesis testing were used to estimate the associations between the 12-month neurodevelopment scores and the test scores obtained at the age of 6. Statistical significance was set at a p-value < 0.05. Results Of the 35 patients who completed the initial study, 20 patients were recruited into the current study (58%). Of them, five patients were lost to medical
follow-up, five were unable to attend the assessment because of geographical location, and five originally agreed to participate but failed to attend the assessment sessions. There were 10 male and 10 female participants assessed. Mean age at assessment was 6.6 years (standard deviation 0.4; range, 5.8–7.2). The degree of surgical complexity was similar to the original cohort (Table 1), although no patients with a functionally single ventricle were in the follow-up group. There was no statistically significant difference in age or weight at surgery, cardiopulmonary bypass time, or requirement for circulatory arrest between the original cohort and the follow-up group. The length of circulatory arrest time did reach statistical significance, with the follow-up group having a greater arrest time (Table 2). One patient with truncus arteriosus underwent further surgery at 2 years of age with an upgrade of right ventricle– pulmonary artery conduit. This patient was not excluded from the study as the surgical procedure was uncomplicated. There was no significant difference between the preoperative or postoperative Bailey Scale of Infant Development Mental or Motor scores between the original cohort and follow-up group (Table 3).
Socioeconomic status Combined annual income was greater than $80,000 in 11 of 20 families, and 7 of 20 (35%) children had at least 1 parent with tertiary qualifications. All results outlining cognitive, neuropsychological, and psychosocial outcomes can be seen in Table 4.
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Table 3. Comparison of baseline Bailey Scale of Infant Development: second edition scores between the original cohort and follow-up group.
Preoperative Mental score [mean (SD)] Motor score [mean (SD)] 12-Month assessment Mental score [mean (SD)] Motor score [mean (SD)]
Original cohort (n = 35)
Follow-up group (n = 20)
p-value
103 (5) 99 (8)
102 (6) 97 (8)
0.51* 0.38*
94 (13) 89 (20)
93 (13) 89 (22)
0.78* 1*
*Paired t-test
Table 4. Means, standard deviations, and ranges of scores across all outcome measures.
Intelligence Full-Scale IQ Verbal IQ Performance IQ Processing speed Q Learning and memory General memory General recognition Literacy and numeracy Word reading Spelling Numerical operations Executive function General executive composite score Behavioural function Internalising problems Externalising problems Total score Psychopathology DSM-IV Total DSM-IV inattentive DSM-IV hyperactive
Mean
SD
Score range
96 95 99 99
12 13 14 11
73–118 72–122 75–118 79–114
94 91
14 17
66–116 61–114
99 101 94
30 15 22
4–146 70–128 13–110
54.80
12.80
25–76
55.85 57.10 58.40
16.38 15.53 19.10
33–93 33–98 24–98
53.58 51.95 54.79
10.64 11.61 10.43
31–72 24–74 35–76
General intelligence All mean scores of intelligence, across each of the measures of cognitive functioning, were found to fall within the average range. No subject had a Full-Scale Intelligence Quotient 2 standard deviations below the mean). However, 7/20 (35%) patients had a Full-Scale Intelligence Quotient in the low-average (six subjects) or borderline range (one subject). The remainder were in the normal range (12 subjects), with only one in the above average range (Fig 1). Memory and learning The majority of the sample had age-appropriate memory and learning skills, as assessed by the Wide Range Assessment of Memory and Learning – second
edition, with all mean scores falling within the average range. However, 20% had some elements in the severely impaired range (>2 standard deviations below the population mean). Of them, one patient had severe impairment of general memory and three patients of general recognition.
Literacy and numeracy Mean literacy scores as assessed by the Abbreviated Wechsler Individual Achievement Test – second edition were within the normal range in all the areas assessed, specifically with word reading, spelling, and numerical operations. It was found that 20% of the patients had moderately impaired numeracy and spelling skills (>1 standard deviation below the population mean). Executive function Executive function within the sample was found to be within the normal range, as measured by the General Executive Composite Score on The Behaviour Rating Inventory of Executive Function. Despite this, 25% of the sample was found to fall within the clinically elevated range in terms of executive function. Behavioural functioning Parental perceptions of the emotional, social, and behavioural functioning of the sample were also found to fall within normal limits, as measured by the Child Behaviour Checklist. A total of 35% were in the borderline or clinical ranges with regard to internalising behaviour problems, externalising behaviour problems, and the Total Score of social, emotional, and behavioural functioning. Psychopathology The Conner’s Parent Rating Scale measured psychopathology in the cohort, specifically with respect to clinical diagnoses of attention disorders. All scores within the Diagnostic and Statistical Manual of
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Figure 1. Bayley Mental and Motor Scores (12-month assessment) compared with FSIQ. Data plotted as SD from normative population mean. (a) Bayley mental score and FSIQ (solid line depicts cohort mean). (b) Bayley motor score and FSIQ (solid line depicts cohort mean). (c) Line graph of Bayley mental score and FSIQ. (d) Line graph of Bayley motor score and FSIQ.
Mental Disorders-IV Total Score, the AttentionDeficit Hyperactivity Disorder Inattentive Score, and the Attention-Deficit Hyperactivity Disorder hyperactive/impulsive Score fell within the normal range. However, a group of 26% fell within the elevated or highly elevated range in the overall Diagnostic and Statistical Manual of Mental Disorders-IV Total Score, 16% fell within the elevated or highly elevated range in the Diagnostic and Statistical Manual of Mental Disorders-IV Attention-Deficit Hyperactivity Disorder Inattentive index, and 26% fell within the elevated or highly elevated range in the Diagnostic and Statistical Manual of Mental Disorders-IV Attention-Deficit Hyperactivity Disorder hyperactive/impulsive index.
Correlation with perioperative factors No statistically significant correlation was found between perioperative factors and the level of intelligence 6 years later (S100-B versus Full Scale Intelligence Quotient r = −0.11 p = 0.62;
cardiopulmonary bypass time versus Full-Scale Intelligence Quotient r = −0.18, p = 0.44; Aortic cross clamp time versus Full Scale Intelligence Quotient r = −0.16, p = 0.48.)
Correlation with 12-month assessment There was a weak association with the Baileys infant scores at 12 months of age and Full-Scale Intelligence Quotient at the age of 6 years that did not reach statistical significance (Baileys mental versus Full-Scale Intelligence Quotient r = 0.37 p = 0.11; Baileys motor versus Full Scale Intelligence Quotient r = 0.39 p = 0.08). The positive predictive value of an abnormal mental score (
© Cambridge University Press, 2014
doi:10.1017/S1047951114001140
Original Article Neurodevelopmental outcome following open heart surgery in infancy: 6-year follow-up Bryn Jones,1,2 Frank Muscara,3 Owen Lloyd,4 Lynne McKinlay,4 Robert Justo5 1
Department of Cardiology, The Royal Children’s Hospital, Melbourne; 2Department of Paediatrics, University of Melbourne; 3Murdoch Children’s Research Institute, Melbourne; 4Queensland Paediatric Rehabilitation Service, Royal Children’s Hospital, Brisbane; 5Queensland Paediatric Cardiac Service, Mater Health Services, Brisbane, Australia Abstract Background: Children undergoing open heart surgery are at risk of neurological injury. A cohort of 35 patients, who had undergone cardiac surgery during infancy, had a significant reduction in Bayley Scale of Infant Development scores at a 12-month assessment. This cohort has now reached an appropriate age to reassess developmental progress. Methods: Detailed psychometric testing was conducted on 20 children from the original cohort using the Weschler Preschool and Primary Scale of Intelligence, the Wide Range Assessment of Memory and Learning, and the Wechsler Individual Achievement Test. Parents completed the Connor’s Rating Scale, the Behaviour Rating Scale of Executive Functioning, and the Child Behaviour Checklist. Results: The mean age of the cohort at assessment was 6.6 (standard deviation 0.4) years. Mean scores on all tests of intelligence, memory, academic achievement, and executive function fell within the average range. Of the children, 20–35% were found to have significant difficulties across these areas. Mean scores in the areas of social, emotional, behavioural, and psychological functioning also fell within the average range. Of the children studied, 35% had clinically significant problems in these areas. There was only a weak association between the 12-month scores and the FullScale Intelligence Quotient at 6 years. Conclusion: Detailed psychometric testing of these children suggests that they generally function in the average range; however, a significant proportion falls below age expectations in all the areas assessed. This highlights the importance of long-term follow-up with routine developmental screening to allow identification of a subgroup that may benefit from early educational and behavioural intervention. Keywords: Heart defects; congenital; paediatric cardiac surgery; developmental outcome Received: 16 April 2014; Accepted: 10 June 2014; First published online: 10 July 2014
C
HILDREN BORN WITH CONGENITAL HEART DISEASE
(CHD) now have an increased chance of longterm survival thanks to advances in surgical techniques.1 Despite these improvements, children undergoing cardiac surgery procedures with cardiopulmonary bypass remain at risk for neurological injury.2,3 Studies have shown that a small percentage (2.3–5.9%) of the patients have acute perioperative events, ranging from transient seizure with no long-term Correspondence to: Dr B. Jones, Department of Cardiology, The Royal Children’s Hospital, Flemington Road, Parkville, Melbourne, Victoria 3052, Australia. Tel: + 61 3 93455713; Fax: + 61 3 93456001. E-mail: [email protected]
sequelae to permanent and severe neurological disabilities.4–7 However, a significantly larger proportion is at risk of longer-term educational and behavioural difficulties, with a pattern of neurodevelopmental problems similar to that seen with preterm infants.8–10 Although it is well established that children with CHD are at risk of longer-term educational and behavioural difficulties, these are often not identified until the child reaches school age, and predictors of these outcomes have not been well established. A previous study conducted by our group11 prospectively examined a cohort of infants who underwent cardiac surgery with cardiopulmonary bypass between
904
Cardiology in the Young
1999 and 2001. A total of 47 infants were enrolled before cardiac surgery and underwent detailed preoperative neurodevelopmental assessment and postoperative monitoring, with 35 of them undergoing follow-up neurodevelopmental assessment at 1 year. The primary aim was to assess the power of perioperative markers associated with neurological injury – electroencephalographic abnormalities, reduced cerebral arterial blood flow velocity, and elevated serum S-100B levels – to predict neurological outcomes at 1 year of age. At 1-year follow-up, there were lower neurodevelopmental scores compared with the preoperative assessments (mean mental scores changing from 103 ± 5 to 04 ± 13 (p = 0.001), and mean motor scores changing from 99 ± 8 to 89 ± 20 (p = 0.004)). However, no association was found between electroencephalographic abnormalities, reduced cerebral arterial blood flow velocity or elevated serum S-100B levels, and impaired neurodevelopmental outcome. This aim of the current study was to assess the neurodevelopmental status of this cohort of children 6 years following their surgery as infants. Specifically, outcomes of interest included current level of cognitive functioning or intelligence, memory and learning skills, level of academic achievement, and executive function, as well as behavioural and psychological functioning. A secondary aim was to determine whether there was any correlation between perioperative risk factors, previous developmental factors, and current level of functioning.
Materials and methods Participants The study is a prospective cohort study and involved the long-term follow-up of a previously assessed cohort 6 years following cardiac surgery. Parents of participants who had been enrolled in the previous study were contacted and their children invited to participate in the follow-up study. The initial study involved 47 infants with structural heart disease aged 16 days–4 months, admitted for cardiac surgery requiring cardiopulmonary bypass at the Prince Charles Hospital, Brisbane, Australia. Exclusion criteria were: known chromosomal abnormalities, associated extracardiac malformations, or an abnormal neurological examination. Of the 47 infants, 35 children had been followed up to 12 months of age. Procedure At study commencement, data were obtained on demographic – age, weight, gestational age – anatomical, and surgical details – cardiac diagnosis, surgical details, requirement for further surgery. In addition, neurodevelopmental data were collated from the first study.
June 2015
All participating children underwent a detailed psychometric assessment performed by two trained neuropsychologists. Parents were asked to complete the questionnaires while their child was being assessed. Family socio-economic status was also assessed with parental questionnaires.
Measures Cognitive function. The Wechsler Primary and Preschool Scale of Intelligence – third edition12 was used to assess intellectual abilities, which in addition to Full-Scale Intelligence Quotient assesses verbal and non-verbal cognitive functioning and speed of information processing. Outcome measures included Full-Scale Intelligence Quotient, Verbal Intelligence Quotient, Performance Intelligence Quotient, and the Processing Speed Quotient (Mean = 100, standard deviation = 15). Memory and learning. Wide Range Assessment of Memory and Learning – second edition13 was used to assess verbal and visual memory and learning, and the recognition of the same information. Outcome measures included a General Memory composite, and a General Recognition Composite (Mean = 100, standard deviation = 15). Academic achievement. The Abbreviated Wechsler Individual Achievement Test – second edition14 was used as a screen of literacy and numeracy functioning. Scores from the spelling, word reading, and numerical operations subtests were used as outcome measures (Mean = 100, standard deviation = 15). Executive function. The Behaviour Rating Inventory of Executive Function–Parent Version15 was used to obtain parent ratings of current functional and behavioural aspects of executive function. The General Executive Composite Score (Mean = 50, standard deviation = 10) was used as an outcome measure or executive function. A higher score indicates a higher level of executive dysfunction, with a score of 65 or above, indicating abnormal elevation. Behavioural functioning. The Child Behaviour Checklist16 assessed parental perceptions of the child’s emotional, social, and behavioural functioning. The Internalising Problems Score, Externalising Problems Score, and the Total Problems Score (Mean = 50, standard deviation = 10) were used as outcome measures. Higher scores indicate greater behavioural problems, with scores between 65 and 69 in the borderline clinical range, and scores of 70 and above in the clinical range. Psychopathology. The Conner’s Parent Rating Scale–Revised17 was also used to assess child psychopathology, with respect to clinical diagnoses of attention disorders. The Diagnostic and Statistical Manual of Mental Disorders-IV Total Score, the
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Jones et al: Neurodevelopmental outcome following open heart surgery
Table 1. Comparison of cardiac diagnosis between original cohort and follow-up group.
Cardiac diagnosis
Original cohort number enrolled (n = 35)
Follow-up group number enrolled (n = 20)
Transposition of the great arteries Tetralogy of Fallot Ventricular septal defect Total anomalous pulmonary venous drainage Common arterial trunk Complex functionally single ventricle
12 9 8 2 2 2
9 5 4 1 1 0
Table 2. Comparison of intraoperative details between original cohort and follow-up group
Age at repair (days) [mean (SD)] Weight at repair (kg) [mean (SD)] Bypass time (minutes) [mean (SD)] Circulatory arrest [n (%)] Circulatory arrest time (minutes) [mean (SD)]
Original cohort (n = 35)
Follow-up group (n = 20)
p-value
57 (15) 4.3 (3.4) 147 (74) 8 (23%) 12 (3)
52 (43) 4.3 (0.9) 155 (55) 5 (25%) 16 (8)
0.53* 1* 0.67* 0.01*
*Paired t-test
Diagnostic and Statistical Manual of Mental Disorders-IV Attention-Deficit Hyperactivity Disorder Inattentive Score, and the Diagnostic and Statistical Manual of Mental Disorders-IV Attention-Deficit Hyperactivity Disorder hyperactive/impulsive Score (Mean = 50, standard deviation = 10) were outcome measures. A higher score indicates greater concern regarding these areas of functioning, with scores of 60–69 considered elevated, and scores above 70 considered highly elevated. The study was approved by the Prince Charles Hospital Human Research Ethics Committee and informed consent was obtained in all cases.
Statistical analysis All statistical tests were conducted using GraphPad Prism version 3.02 for Windows (GraphPad Software, San Diego, United States of America. http:// www.graphpad.com). Values are expressed as mean (standard deviation) or number (%) as appropriate. For comparative data, two-tailed paired t-tests were used. Spearman’s correlation coefficients, with twotailed hypothesis testing were used to estimate the associations between the 12-month neurodevelopment scores and the test scores obtained at the age of 6. Statistical significance was set at a p-value < 0.05. Results Of the 35 patients who completed the initial study, 20 patients were recruited into the current study (58%). Of them, five patients were lost to medical
follow-up, five were unable to attend the assessment because of geographical location, and five originally agreed to participate but failed to attend the assessment sessions. There were 10 male and 10 female participants assessed. Mean age at assessment was 6.6 years (standard deviation 0.4; range, 5.8–7.2). The degree of surgical complexity was similar to the original cohort (Table 1), although no patients with a functionally single ventricle were in the follow-up group. There was no statistically significant difference in age or weight at surgery, cardiopulmonary bypass time, or requirement for circulatory arrest between the original cohort and the follow-up group. The length of circulatory arrest time did reach statistical significance, with the follow-up group having a greater arrest time (Table 2). One patient with truncus arteriosus underwent further surgery at 2 years of age with an upgrade of right ventricle– pulmonary artery conduit. This patient was not excluded from the study as the surgical procedure was uncomplicated. There was no significant difference between the preoperative or postoperative Bailey Scale of Infant Development Mental or Motor scores between the original cohort and follow-up group (Table 3).
Socioeconomic status Combined annual income was greater than $80,000 in 11 of 20 families, and 7 of 20 (35%) children had at least 1 parent with tertiary qualifications. All results outlining cognitive, neuropsychological, and psychosocial outcomes can be seen in Table 4.
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Table 3. Comparison of baseline Bailey Scale of Infant Development: second edition scores between the original cohort and follow-up group.
Preoperative Mental score [mean (SD)] Motor score [mean (SD)] 12-Month assessment Mental score [mean (SD)] Motor score [mean (SD)]
Original cohort (n = 35)
Follow-up group (n = 20)
p-value
103 (5) 99 (8)
102 (6) 97 (8)
0.51* 0.38*
94 (13) 89 (20)
93 (13) 89 (22)
0.78* 1*
*Paired t-test
Table 4. Means, standard deviations, and ranges of scores across all outcome measures.
Intelligence Full-Scale IQ Verbal IQ Performance IQ Processing speed Q Learning and memory General memory General recognition Literacy and numeracy Word reading Spelling Numerical operations Executive function General executive composite score Behavioural function Internalising problems Externalising problems Total score Psychopathology DSM-IV Total DSM-IV inattentive DSM-IV hyperactive
Mean
SD
Score range
96 95 99 99
12 13 14 11
73–118 72–122 75–118 79–114
94 91
14 17
66–116 61–114
99 101 94
30 15 22
4–146 70–128 13–110
54.80
12.80
25–76
55.85 57.10 58.40
16.38 15.53 19.10
33–93 33–98 24–98
53.58 51.95 54.79
10.64 11.61 10.43
31–72 24–74 35–76
General intelligence All mean scores of intelligence, across each of the measures of cognitive functioning, were found to fall within the average range. No subject had a Full-Scale Intelligence Quotient 2 standard deviations below the mean). However, 7/20 (35%) patients had a Full-Scale Intelligence Quotient in the low-average (six subjects) or borderline range (one subject). The remainder were in the normal range (12 subjects), with only one in the above average range (Fig 1). Memory and learning The majority of the sample had age-appropriate memory and learning skills, as assessed by the Wide Range Assessment of Memory and Learning – second
edition, with all mean scores falling within the average range. However, 20% had some elements in the severely impaired range (>2 standard deviations below the population mean). Of them, one patient had severe impairment of general memory and three patients of general recognition.
Literacy and numeracy Mean literacy scores as assessed by the Abbreviated Wechsler Individual Achievement Test – second edition were within the normal range in all the areas assessed, specifically with word reading, spelling, and numerical operations. It was found that 20% of the patients had moderately impaired numeracy and spelling skills (>1 standard deviation below the population mean). Executive function Executive function within the sample was found to be within the normal range, as measured by the General Executive Composite Score on The Behaviour Rating Inventory of Executive Function. Despite this, 25% of the sample was found to fall within the clinically elevated range in terms of executive function. Behavioural functioning Parental perceptions of the emotional, social, and behavioural functioning of the sample were also found to fall within normal limits, as measured by the Child Behaviour Checklist. A total of 35% were in the borderline or clinical ranges with regard to internalising behaviour problems, externalising behaviour problems, and the Total Score of social, emotional, and behavioural functioning. Psychopathology The Conner’s Parent Rating Scale measured psychopathology in the cohort, specifically with respect to clinical diagnoses of attention disorders. All scores within the Diagnostic and Statistical Manual of
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907
Figure 1. Bayley Mental and Motor Scores (12-month assessment) compared with FSIQ. Data plotted as SD from normative population mean. (a) Bayley mental score and FSIQ (solid line depicts cohort mean). (b) Bayley motor score and FSIQ (solid line depicts cohort mean). (c) Line graph of Bayley mental score and FSIQ. (d) Line graph of Bayley motor score and FSIQ.
Mental Disorders-IV Total Score, the AttentionDeficit Hyperactivity Disorder Inattentive Score, and the Attention-Deficit Hyperactivity Disorder hyperactive/impulsive Score fell within the normal range. However, a group of 26% fell within the elevated or highly elevated range in the overall Diagnostic and Statistical Manual of Mental Disorders-IV Total Score, 16% fell within the elevated or highly elevated range in the Diagnostic and Statistical Manual of Mental Disorders-IV Attention-Deficit Hyperactivity Disorder Inattentive index, and 26% fell within the elevated or highly elevated range in the Diagnostic and Statistical Manual of Mental Disorders-IV Attention-Deficit Hyperactivity Disorder hyperactive/impulsive index.
Correlation with perioperative factors No statistically significant correlation was found between perioperative factors and the level of intelligence 6 years later (S100-B versus Full Scale Intelligence Quotient r = −0.11 p = 0.62;
cardiopulmonary bypass time versus Full-Scale Intelligence Quotient r = −0.18, p = 0.44; Aortic cross clamp time versus Full Scale Intelligence Quotient r = −0.16, p = 0.48.)
Correlation with 12-month assessment There was a weak association with the Baileys infant scores at 12 months of age and Full-Scale Intelligence Quotient at the age of 6 years that did not reach statistical significance (Baileys mental versus Full-Scale Intelligence Quotient r = 0.37 p = 0.11; Baileys motor versus Full Scale Intelligence Quotient r = 0.39 p = 0.08). The positive predictive value of an abnormal mental score (
