373
ORIGINAL ARTICLES Impact of Fetal Development on Neurocognitive Performance of Adolescents with Cyanotic and Acyanotic Congenital Heart Disease Samantha M. Matos,*† Sofia Sarmento,*† Sara Moreira,*† Maria Manuela Pereira,*† Jorge Quintas, PhD,‡ Bruno Peixoto, PhD,*† José Carlos Areias, MD, PhD,§¶** and Maria Emília G. Areias, PhD*** *Department of Psychology, Higher Institute for Health Sciences-North (CESPU), †IINFACTS (CESPU), Gandra, ‡Faculty of Law, University of Porto, §Department of Pediatric Cardiology, Hospital S. João, ¶Porto Medical School, University of Porto and **Cardiovascular Research and Development Unit, University of Porto, Porto ABSTRACT
Background. Our aims were to evaluate the neurocognitive performance in adolescents with congenital heart disease (CHD) and to determine whether parameters of fetal development evaluated in neonates, such as head circumference, length, weight, and Apgar scores, are somehow related to their neurocognitive performance. Methods. We evaluated 77 CHD patients (43 males) aged from 13 to 18 years old (mean = 15.04 ± 1.86), 46 cyanotic, 23 with tetralogy of Fallot (TF), 23 with transposition of the great arteries (TGA) and 31 acyanotic with ventricular septal defect (VSD) enrolled in this study. The control group included 16 healthy children (11 males) ages ranging from 13 to 18 years old (mean = 15.69 years ± 1.44 years). All assessment measures for CHD patients were once obtained in a tertiary hospital; the control group was evaluated in school. Neuropsychological assessment included Wechsler’s Digit Test, direct and reverse (WDD and WDR) and Symbol Search, Rey’s Complex Figure (RCF), BADS’s Key Searching Test, Color-Word Stroop Test (CWS), Trail Making Test (TMT), and Logical Memory Task (LMT). We evaluated some fetal parameters, such as head circumference, weight and length assessed at birth, and neonatal parameters, such as Apgar scores at 1 and 5 minutes after birth. We also registered some surgical parameters, such as the age at first operation and the number of surgeries. Results. CHD patients compared with control group showed lower scores on every test, except for logical memory task. Patients with VSD when compared with patients with TF and TGA showed better results in all neuropsychological tests, although the only significant differences were in RCF, copy (F = 4936; P = .010). Several correlations were apparent between fetal/neonatal parameters and neuropsychological abilities in each type of CHD. However, head circumference at birth stands as the main correlation with cognitive development later on in all kinds of CHD (WDD: rho = .339, P = .011; RCF, copy: rho = 0.297, P = .027; CWS, interference: rho = 0.283, P = .036; TMT-A: rho = −0.321, P = .017). We analyzed the predicting relevance of several variables to cognitive performance of adolescents with CHD and confirmed that “cyanosis” stands as the main predictor (â = −4.758; t = −2.622; P = .011). Conclusions. Adolescents with CHD have worse neuropsychological performance than the control group, mainly the cyanotic patients. Fetal circulation seems to have impact on cerebral and somatic growth, predicting cognitive impairment in adolescents with CHD. Key Words. Fetal Development; Neurocognitive Functioning; Neonatal Variables; Congenital Heart Disease
Introduction
Funding This research was supported by a grant from CESPU.
© 2013 Wiley Periodicals, Inc.
C
ongenital heart disease has been considered as the most common cause of child morbidity and mortality.1 Congenit Heart Dis. 2014;9:373–381
374 In recent decades, advances made in surgical interventions and treatment in patients with CHD have greatly contributed to increase the life expectancy of these children. However, over half of these children will over time end up developing some type of neurological damage.2–4 In available literature, different studies have described that there are changes in cognitive development of young people suffering from CHD. These consequences are related to perioperative factors (syndromes, extracorporeal circulation during surgery, and postsurgical complications).5 However, according to some studies, neurobehavioral abnormalities, such as hypotonic, agitation, motor asymmetry, lethargy, and autistic characteristics, were found prior to surgery in over 50% of newborns (less than a month old) and 38% of children (between 1 month old and 2 years old) with CHD. These abnormalities usually persist or intensify in the postoperative period, when cranial nerve damage may also occur.6,7 The fetal hypoxia affects the normal development of the brain, namely in the hippocampus (a brain structure responsible for converting shortterm memory into long-term memory) and the cerebral cortex (the brain structure responsible for cognitive areas related to memory, attention, language, perception, and thought).8 This may be due to the fact that congenital cardiac malformations and abnormalities in fetal growth are related.9,10 In fact, newborns with certain forms of CHD are born with smaller head circumferences possibly indicating impaired brain growth. The developing brain is highly metabolic and dependent upon the heart for delivery of oxygen and nutrients. The heart in turn receives innervation and control from the autonomic nervous system, and therefore, the disruption of organogenesis in one organ will have significant effects for the other. The existence of CHD will increase the chances of blood flow abnormalities in the fetus, resulting in a compromised brain development due to the complex relations between common cells, genetic programming, physiological consequences of cerebral blood flow alterations, and the dynamic of oxygen distribution during brain development.10,11 This can be seen as strong evidence that these factors have an important role in cerebral growth.12 When the fetal oxygenation is compromised, there is a blood redistribution to the cerebral circulation, a phenomenon known as brain sparing,1 resulting primarily in a pattern of global distribution of the somatic growth, with preservation of the head growth.10 Congenit Heart Dis. 2014;9:373–381
Matos et al. This hemodynamic growth is represented by the diastolic flow in the cerebral arteries and the decrease of diastolic flow in the descending and umbilical aorta.1 It is believed that many brain areas may be better protected than others. This mechanism has been found to be a contributor to an adverse neurological development, as the cerebral vasodilatation occurs when there is a compromise in the fetal oxygenation. This protection mechanism does not seem to be enough to keep a normal brain development and growth in prolonged stress situations in the uterus. In a normal fetal blood circulation, the oxygenated blood is taken to the brain, and the deoxygenized blood goes to the placenta.1 As previously stated, studies have shown that abnormalities in blood flow occuring in congenital heart disease, such as hypoplasic left heart syndrome, transposition of the great arteries (TGA), and tetralogy of Fallot (TF), may contribute to an abnormal brain development,1,10,13 or an acquired brain injury. However, research on fetal brain development is in its earlier stages, giving scarce information about the brain at term age. Many factors are believed to explain the low weight at birth, including genetic syndromes, placenta insufficiency, and intrauterine growth restriction. All these may increase the risk of neurodevelopment delays. Recently, Gaynor et al.14 showed that, in general, factors inherent to the patient, such as weight at birth, head circumference at birth, and the Apgar score in the first and fifth minute, explain better the vulnerability of mental and psychomotor growth than the intraoperative factors (weight in surgery, cooling time, deep hypothermic circulatory arrest time, cardiopulmonary bypass time, and lowest nasopharyngeal temperature). Thus, following these observations, the main objectives of our study were to evaluate the neurocognitive performance of adolescents and young adults with CHD, trying to relate abnormal neonatal parameters (some indicating fetal brain development assessed at birth, such as cephalic perimeter, weight and length, and others, such as the Apgar scores), with specific neurocognitive deficits found later on in the patients’ life, and to compare cyanotic (TF and TGA) and acyanotic (ventricular septal defect [VSD]) patients regarding their neurocognitive performance. Inside the cyanotic group, we aimed also to analyze the importance of the age at first surgery.
375
Neurocognitive Performance in Patients with CHD
Patients and Methods The study enrolled 93 participants, between 13 and 18 years of age, divided in two groups: a CHD group, comprising 77 patients (43 males) recruited from the outpatient pediatric cardiology clinic at the Hospital de Sao João (Porto), with mean age 15.04 ± 1.86; and a group control (CG), made up of 16 adolescents (11 males) from several schools in the Porto city area (Table 1). The CHD group is further divided into three groups, each corresponding to a different type of congenital heart disease: (1) TGA (n = 23); (2) TF (n = 23); (3) VSD (n = 31). Tables 1 and 2 provide further detail on the characteristics of the sample. Control group (CG) and CHD group do not differ according to age (P = .197), gender (χ2 = 0.906; P = .253), and years of education (P = .055). The same is true for the three subgroups of CHD, regarding age (P = .841), gender (χ2 = 3.195; P = .202), and years of education (P = .792). Complete medical records were available for all the patients, the clinical files being provided by the department of Cardiology or Pediatric Cardiology. In total, 19 patients with VSD were never submitted to any kind of surgical procedure, whereas eight had only one surgery and four had two surgeries; among those 12, four were submitted to the first surgery between 1 and 6 months after birth, six between 7 and 12 months, one between 19 and 24 months, and one with more than 36 months. From 23 patients with TGA, 12 had four surgeries, one had nine, four were submitted to three, Table 1.
Characterization of the Participants of Our Study
Age (M ± SD) Gender (male/female) Education (M ± SD)
C (n = 16)
CHD (n = 77)
15.69 y ± 1.44 11/5 10.13 y ± 1,36
15.09 y ± 1.71 43/34 9.13 y ± 1.95
C = Control group. CHD = Group including patients with congenital heart disease.
Table 2.
five to two, and one was only submitted to one surgery. The first operation was performed at 1 month after birth, for 21, and between 1 and 6 months for two patients. From 23 patients with TF, six were operated twice, 10 were submitted to three surgeries, and the remaining seven to four; the first surgery was for 10 in the first month, for seven between 1 and 6 months old, for three between 7 and 12 months, for one between 13 and 18 months, and finally for two later than 36 months.
Neuropsychological Assessment In order to collect all necessary information for this study, all participants underwent a brief neuropsychological assessment, designed to evaluate a number of neurocognitive functions over a short period of time. Different tests were used for this purpose such as, Wechsler’s Digit Test, in direct and indirect form, focused on the assessment of immediate auditory–verbal attention and working memory, respectively; Wechsler’s Symbol Search, used to evaluate psychomotor performance, speed of execution, perceptive organization. and persistence. Rey’s complex figure, copy and reproduction from memory 3 minutes after image exposure, was used in order to assess visual constructional ability and visual constructional memory. The Key Search Test, from the Behavioral Assessment of the Dysexecutive Syndrome for children, focuses on the evaluation of the capability for efficient planning. Color-Word Stroop Test was used to assess attention efficiency. Trail Making Test (TMT), part A (TMT-A) focuses on the evaluation of visual spatial orientation and psychomotor speed, whereas part B (TMT-B) is to assess divided attention. Finally, Wechsler’s Logical Memory Task was used to evaluate verbal memory.
Characteristics of the CHD Subgroups Including the Parameters of Fetal Development
Age (M ± SD) Gender (male/female) Education (M ± SD) Head circumference (M ± SD) Apgar 1 (M ± SD) Apgar 2 (M ± SD) Weight (M ± SD) Length (M ± SD)
TGA (n = 23)
TF (n = 23)
VSD (n = 31)
14.91 y ± 1.95 16/7 8.91 y ± 2.03 33.87 ± 1.51 8.06 ± 1.20 9.29 ± 0.99 3.17 ± 0.44 48.05 ± 2.55
15.17 y ± 1.8 13/10 9.30 y ± 2.12 32.96 ± 2.93 7.82 ± 2.01 9.53 ± 0.87 2.87 ± 0.76 46.79 ± 5.25
15.16 y ± 1.43 14/17 9.16 y ± 1.79 34.40 ± 2.38 7.50 ± 2.39 9.86 ± 0.36 3.21 ± 0.66 48.11 ± 3.11
TGA, group including patients with transposition of the great arteries; TF, group including patients with tetralogy of Fallot; VSD, group including patients with ventricular septal defect; Apgar 1, Apgar index at 1 minute after birth; Apgar 2, Apgar index at 5 minutes after birth.
Congenit Heart Dis. 2014;9:373–381
376
Assessment of Fetal and Neonatal Parameters To assess fetal development at the long run, we registered the parameters of cephalic perimeter, weight, and length at birth. We also collected the Apgar scores at 1 and 5 minutes. Procedure Prospective participants were contacted before or after scheduled hospital appointments. The subjects were asked to participate after being fully informed of the objectives and procedures of the investigation. The parents (when they were under 18 years old) or the patients who agreed completed an informed consent form approved by the hospital’s ethical committee, which followed international conventions guaranteeing the rights of the patients. The interview and assessment happened on the spot. Design All the assessment measures were obtained on a single occasion. Clinical data were collected retrospectively using each patient’s clinical record, with assistance from hospital medical staff. Statistical Analysis Statistical analysis was carried out using the program IBM SPSS Statistics for Windows, version 21 (Chicago, IL, USA). A comparison of the obtained results on the neuropsychological tests between the control and CHD group was made through Mann–Whitney U-test and within the different CHD subgroups was made through a one-way analysis of variance. We used the Student’s t-test to analyze the impact of parents’ school achievement in neuropsychological performance of CHD adolescents. The Spearman correlations were used in order to correlate neonatal variables (weight, length, cephalic perimeter, and Apgar indexes) with the results obtained by the CHD group and subgroups. To obtain an overall performance index on neuropsychological tests, we performed the summing of z-scores for each participant in each test (inverting the TMT-A and TMT-B data, where a higher score reveals a worse performance, contrariwise to the other tests). Finally, an independent stepwise regression analysis was conducted to determine the relationship between the independent variables (head circumference, weight, and length at birth, Apgar scores at 1 and 5 minutes, kind of congenital heart disease, cyanotic vs. acyanotic disease) and neuropsychological performance. Congenit Heart Dis. 2014;9:373–381
Matos et al. Results
Table 1 presents the demographic characteristics of the participants of our study, both in the CHD and in the CGs. Regarding the school achievements of caregivers in the CHD group, we found that 73.8% of fathers and mothers completed 9 years in school or less, and only the remaining completed a higher grade (three last years in high school, bachelor, master or doctor). Table 2 presents the demographic characteristics and the fetal and neonatal parameters of the participants in each of the subgroups of CHD (TGA, TF, and VSD). We analyzed the impact of years that caregivers completed in school over the neuropsychological performance of adolescents with CHD and found that these variables are not related (with a significance value of 0.560). Comparing the performance of the control and CHD groups, in the neuropsychological tests, we found significant differences between the groups that can be seen in Table 3, with CG leading with better results across the various tests, with exception of the Logical Memory task. Table 4 provides the results obtained in the neuropsychological tests by the subgroups of CHD (VSD, TF and TGA). There, we can see that the VSD subgroup shows better results compared with the cyanotic subgroups (TF and TGA), but the only statistically significant difference was in Rey’s Complex Figure, memory test (reproduction from memory 3 minutes after image exposure) (RCFm) (P = .010). We analyzed the correlations between indices of fetal brain development and neonatal paramTable 3. Comparison of Results Obtained by the Control and the CHD Groups in Different Neuropsychological Tasks Control Group
WDD WDR RCFc RCFm WSS BKS StroopW StroopC StroopI TMT-A TMT-B MLT Total performance *P ≤ .05 **P ≤ .01.
CHD Group
n = 16
n = 77
Mean Rank
Mean Rank
u
P
69.09 75.09 75.97 76.19 32.25 75.47 76.31 71.44 77.16 14.22 16.66 52.50 82.31
42.41 41.16 40.98 40.94 50.06 41.08 40.91 41.92 40.73 53.81 53.31 45.86 39.66
262.5 166.5 152.5 149.0 380.0 160.5 147.0 225.0 133.5 91.5 130.5 528.0 51.0
ORIGINAL ARTICLES Impact of Fetal Development on Neurocognitive Performance of Adolescents with Cyanotic and Acyanotic Congenital Heart Disease Samantha M. Matos,*† Sofia Sarmento,*† Sara Moreira,*† Maria Manuela Pereira,*† Jorge Quintas, PhD,‡ Bruno Peixoto, PhD,*† José Carlos Areias, MD, PhD,§¶** and Maria Emília G. Areias, PhD*** *Department of Psychology, Higher Institute for Health Sciences-North (CESPU), †IINFACTS (CESPU), Gandra, ‡Faculty of Law, University of Porto, §Department of Pediatric Cardiology, Hospital S. João, ¶Porto Medical School, University of Porto and **Cardiovascular Research and Development Unit, University of Porto, Porto ABSTRACT
Background. Our aims were to evaluate the neurocognitive performance in adolescents with congenital heart disease (CHD) and to determine whether parameters of fetal development evaluated in neonates, such as head circumference, length, weight, and Apgar scores, are somehow related to their neurocognitive performance. Methods. We evaluated 77 CHD patients (43 males) aged from 13 to 18 years old (mean = 15.04 ± 1.86), 46 cyanotic, 23 with tetralogy of Fallot (TF), 23 with transposition of the great arteries (TGA) and 31 acyanotic with ventricular septal defect (VSD) enrolled in this study. The control group included 16 healthy children (11 males) ages ranging from 13 to 18 years old (mean = 15.69 years ± 1.44 years). All assessment measures for CHD patients were once obtained in a tertiary hospital; the control group was evaluated in school. Neuropsychological assessment included Wechsler’s Digit Test, direct and reverse (WDD and WDR) and Symbol Search, Rey’s Complex Figure (RCF), BADS’s Key Searching Test, Color-Word Stroop Test (CWS), Trail Making Test (TMT), and Logical Memory Task (LMT). We evaluated some fetal parameters, such as head circumference, weight and length assessed at birth, and neonatal parameters, such as Apgar scores at 1 and 5 minutes after birth. We also registered some surgical parameters, such as the age at first operation and the number of surgeries. Results. CHD patients compared with control group showed lower scores on every test, except for logical memory task. Patients with VSD when compared with patients with TF and TGA showed better results in all neuropsychological tests, although the only significant differences were in RCF, copy (F = 4936; P = .010). Several correlations were apparent between fetal/neonatal parameters and neuropsychological abilities in each type of CHD. However, head circumference at birth stands as the main correlation with cognitive development later on in all kinds of CHD (WDD: rho = .339, P = .011; RCF, copy: rho = 0.297, P = .027; CWS, interference: rho = 0.283, P = .036; TMT-A: rho = −0.321, P = .017). We analyzed the predicting relevance of several variables to cognitive performance of adolescents with CHD and confirmed that “cyanosis” stands as the main predictor (â = −4.758; t = −2.622; P = .011). Conclusions. Adolescents with CHD have worse neuropsychological performance than the control group, mainly the cyanotic patients. Fetal circulation seems to have impact on cerebral and somatic growth, predicting cognitive impairment in adolescents with CHD. Key Words. Fetal Development; Neurocognitive Functioning; Neonatal Variables; Congenital Heart Disease
Introduction
Funding This research was supported by a grant from CESPU.
© 2013 Wiley Periodicals, Inc.
C
ongenital heart disease has been considered as the most common cause of child morbidity and mortality.1 Congenit Heart Dis. 2014;9:373–381
374 In recent decades, advances made in surgical interventions and treatment in patients with CHD have greatly contributed to increase the life expectancy of these children. However, over half of these children will over time end up developing some type of neurological damage.2–4 In available literature, different studies have described that there are changes in cognitive development of young people suffering from CHD. These consequences are related to perioperative factors (syndromes, extracorporeal circulation during surgery, and postsurgical complications).5 However, according to some studies, neurobehavioral abnormalities, such as hypotonic, agitation, motor asymmetry, lethargy, and autistic characteristics, were found prior to surgery in over 50% of newborns (less than a month old) and 38% of children (between 1 month old and 2 years old) with CHD. These abnormalities usually persist or intensify in the postoperative period, when cranial nerve damage may also occur.6,7 The fetal hypoxia affects the normal development of the brain, namely in the hippocampus (a brain structure responsible for converting shortterm memory into long-term memory) and the cerebral cortex (the brain structure responsible for cognitive areas related to memory, attention, language, perception, and thought).8 This may be due to the fact that congenital cardiac malformations and abnormalities in fetal growth are related.9,10 In fact, newborns with certain forms of CHD are born with smaller head circumferences possibly indicating impaired brain growth. The developing brain is highly metabolic and dependent upon the heart for delivery of oxygen and nutrients. The heart in turn receives innervation and control from the autonomic nervous system, and therefore, the disruption of organogenesis in one organ will have significant effects for the other. The existence of CHD will increase the chances of blood flow abnormalities in the fetus, resulting in a compromised brain development due to the complex relations between common cells, genetic programming, physiological consequences of cerebral blood flow alterations, and the dynamic of oxygen distribution during brain development.10,11 This can be seen as strong evidence that these factors have an important role in cerebral growth.12 When the fetal oxygenation is compromised, there is a blood redistribution to the cerebral circulation, a phenomenon known as brain sparing,1 resulting primarily in a pattern of global distribution of the somatic growth, with preservation of the head growth.10 Congenit Heart Dis. 2014;9:373–381
Matos et al. This hemodynamic growth is represented by the diastolic flow in the cerebral arteries and the decrease of diastolic flow in the descending and umbilical aorta.1 It is believed that many brain areas may be better protected than others. This mechanism has been found to be a contributor to an adverse neurological development, as the cerebral vasodilatation occurs when there is a compromise in the fetal oxygenation. This protection mechanism does not seem to be enough to keep a normal brain development and growth in prolonged stress situations in the uterus. In a normal fetal blood circulation, the oxygenated blood is taken to the brain, and the deoxygenized blood goes to the placenta.1 As previously stated, studies have shown that abnormalities in blood flow occuring in congenital heart disease, such as hypoplasic left heart syndrome, transposition of the great arteries (TGA), and tetralogy of Fallot (TF), may contribute to an abnormal brain development,1,10,13 or an acquired brain injury. However, research on fetal brain development is in its earlier stages, giving scarce information about the brain at term age. Many factors are believed to explain the low weight at birth, including genetic syndromes, placenta insufficiency, and intrauterine growth restriction. All these may increase the risk of neurodevelopment delays. Recently, Gaynor et al.14 showed that, in general, factors inherent to the patient, such as weight at birth, head circumference at birth, and the Apgar score in the first and fifth minute, explain better the vulnerability of mental and psychomotor growth than the intraoperative factors (weight in surgery, cooling time, deep hypothermic circulatory arrest time, cardiopulmonary bypass time, and lowest nasopharyngeal temperature). Thus, following these observations, the main objectives of our study were to evaluate the neurocognitive performance of adolescents and young adults with CHD, trying to relate abnormal neonatal parameters (some indicating fetal brain development assessed at birth, such as cephalic perimeter, weight and length, and others, such as the Apgar scores), with specific neurocognitive deficits found later on in the patients’ life, and to compare cyanotic (TF and TGA) and acyanotic (ventricular septal defect [VSD]) patients regarding their neurocognitive performance. Inside the cyanotic group, we aimed also to analyze the importance of the age at first surgery.
375
Neurocognitive Performance in Patients with CHD
Patients and Methods The study enrolled 93 participants, between 13 and 18 years of age, divided in two groups: a CHD group, comprising 77 patients (43 males) recruited from the outpatient pediatric cardiology clinic at the Hospital de Sao João (Porto), with mean age 15.04 ± 1.86; and a group control (CG), made up of 16 adolescents (11 males) from several schools in the Porto city area (Table 1). The CHD group is further divided into three groups, each corresponding to a different type of congenital heart disease: (1) TGA (n = 23); (2) TF (n = 23); (3) VSD (n = 31). Tables 1 and 2 provide further detail on the characteristics of the sample. Control group (CG) and CHD group do not differ according to age (P = .197), gender (χ2 = 0.906; P = .253), and years of education (P = .055). The same is true for the three subgroups of CHD, regarding age (P = .841), gender (χ2 = 3.195; P = .202), and years of education (P = .792). Complete medical records were available for all the patients, the clinical files being provided by the department of Cardiology or Pediatric Cardiology. In total, 19 patients with VSD were never submitted to any kind of surgical procedure, whereas eight had only one surgery and four had two surgeries; among those 12, four were submitted to the first surgery between 1 and 6 months after birth, six between 7 and 12 months, one between 19 and 24 months, and one with more than 36 months. From 23 patients with TGA, 12 had four surgeries, one had nine, four were submitted to three, Table 1.
Characterization of the Participants of Our Study
Age (M ± SD) Gender (male/female) Education (M ± SD)
C (n = 16)
CHD (n = 77)
15.69 y ± 1.44 11/5 10.13 y ± 1,36
15.09 y ± 1.71 43/34 9.13 y ± 1.95
C = Control group. CHD = Group including patients with congenital heart disease.
Table 2.
five to two, and one was only submitted to one surgery. The first operation was performed at 1 month after birth, for 21, and between 1 and 6 months for two patients. From 23 patients with TF, six were operated twice, 10 were submitted to three surgeries, and the remaining seven to four; the first surgery was for 10 in the first month, for seven between 1 and 6 months old, for three between 7 and 12 months, for one between 13 and 18 months, and finally for two later than 36 months.
Neuropsychological Assessment In order to collect all necessary information for this study, all participants underwent a brief neuropsychological assessment, designed to evaluate a number of neurocognitive functions over a short period of time. Different tests were used for this purpose such as, Wechsler’s Digit Test, in direct and indirect form, focused on the assessment of immediate auditory–verbal attention and working memory, respectively; Wechsler’s Symbol Search, used to evaluate psychomotor performance, speed of execution, perceptive organization. and persistence. Rey’s complex figure, copy and reproduction from memory 3 minutes after image exposure, was used in order to assess visual constructional ability and visual constructional memory. The Key Search Test, from the Behavioral Assessment of the Dysexecutive Syndrome for children, focuses on the evaluation of the capability for efficient planning. Color-Word Stroop Test was used to assess attention efficiency. Trail Making Test (TMT), part A (TMT-A) focuses on the evaluation of visual spatial orientation and psychomotor speed, whereas part B (TMT-B) is to assess divided attention. Finally, Wechsler’s Logical Memory Task was used to evaluate verbal memory.
Characteristics of the CHD Subgroups Including the Parameters of Fetal Development
Age (M ± SD) Gender (male/female) Education (M ± SD) Head circumference (M ± SD) Apgar 1 (M ± SD) Apgar 2 (M ± SD) Weight (M ± SD) Length (M ± SD)
TGA (n = 23)
TF (n = 23)
VSD (n = 31)
14.91 y ± 1.95 16/7 8.91 y ± 2.03 33.87 ± 1.51 8.06 ± 1.20 9.29 ± 0.99 3.17 ± 0.44 48.05 ± 2.55
15.17 y ± 1.8 13/10 9.30 y ± 2.12 32.96 ± 2.93 7.82 ± 2.01 9.53 ± 0.87 2.87 ± 0.76 46.79 ± 5.25
15.16 y ± 1.43 14/17 9.16 y ± 1.79 34.40 ± 2.38 7.50 ± 2.39 9.86 ± 0.36 3.21 ± 0.66 48.11 ± 3.11
TGA, group including patients with transposition of the great arteries; TF, group including patients with tetralogy of Fallot; VSD, group including patients with ventricular septal defect; Apgar 1, Apgar index at 1 minute after birth; Apgar 2, Apgar index at 5 minutes after birth.
Congenit Heart Dis. 2014;9:373–381
376
Assessment of Fetal and Neonatal Parameters To assess fetal development at the long run, we registered the parameters of cephalic perimeter, weight, and length at birth. We also collected the Apgar scores at 1 and 5 minutes. Procedure Prospective participants were contacted before or after scheduled hospital appointments. The subjects were asked to participate after being fully informed of the objectives and procedures of the investigation. The parents (when they were under 18 years old) or the patients who agreed completed an informed consent form approved by the hospital’s ethical committee, which followed international conventions guaranteeing the rights of the patients. The interview and assessment happened on the spot. Design All the assessment measures were obtained on a single occasion. Clinical data were collected retrospectively using each patient’s clinical record, with assistance from hospital medical staff. Statistical Analysis Statistical analysis was carried out using the program IBM SPSS Statistics for Windows, version 21 (Chicago, IL, USA). A comparison of the obtained results on the neuropsychological tests between the control and CHD group was made through Mann–Whitney U-test and within the different CHD subgroups was made through a one-way analysis of variance. We used the Student’s t-test to analyze the impact of parents’ school achievement in neuropsychological performance of CHD adolescents. The Spearman correlations were used in order to correlate neonatal variables (weight, length, cephalic perimeter, and Apgar indexes) with the results obtained by the CHD group and subgroups. To obtain an overall performance index on neuropsychological tests, we performed the summing of z-scores for each participant in each test (inverting the TMT-A and TMT-B data, where a higher score reveals a worse performance, contrariwise to the other tests). Finally, an independent stepwise regression analysis was conducted to determine the relationship between the independent variables (head circumference, weight, and length at birth, Apgar scores at 1 and 5 minutes, kind of congenital heart disease, cyanotic vs. acyanotic disease) and neuropsychological performance. Congenit Heart Dis. 2014;9:373–381
Matos et al. Results
Table 1 presents the demographic characteristics of the participants of our study, both in the CHD and in the CGs. Regarding the school achievements of caregivers in the CHD group, we found that 73.8% of fathers and mothers completed 9 years in school or less, and only the remaining completed a higher grade (three last years in high school, bachelor, master or doctor). Table 2 presents the demographic characteristics and the fetal and neonatal parameters of the participants in each of the subgroups of CHD (TGA, TF, and VSD). We analyzed the impact of years that caregivers completed in school over the neuropsychological performance of adolescents with CHD and found that these variables are not related (with a significance value of 0.560). Comparing the performance of the control and CHD groups, in the neuropsychological tests, we found significant differences between the groups that can be seen in Table 3, with CG leading with better results across the various tests, with exception of the Logical Memory task. Table 4 provides the results obtained in the neuropsychological tests by the subgroups of CHD (VSD, TF and TGA). There, we can see that the VSD subgroup shows better results compared with the cyanotic subgroups (TF and TGA), but the only statistically significant difference was in Rey’s Complex Figure, memory test (reproduction from memory 3 minutes after image exposure) (RCFm) (P = .010). We analyzed the correlations between indices of fetal brain development and neonatal paramTable 3. Comparison of Results Obtained by the Control and the CHD Groups in Different Neuropsychological Tasks Control Group
WDD WDR RCFc RCFm WSS BKS StroopW StroopC StroopI TMT-A TMT-B MLT Total performance *P ≤ .05 **P ≤ .01.
CHD Group
n = 16
n = 77
Mean Rank
Mean Rank
u
P
69.09 75.09 75.97 76.19 32.25 75.47 76.31 71.44 77.16 14.22 16.66 52.50 82.31
42.41 41.16 40.98 40.94 50.06 41.08 40.91 41.92 40.73 53.81 53.31 45.86 39.66
262.5 166.5 152.5 149.0 380.0 160.5 147.0 225.0 133.5 91.5 130.5 528.0 51.0
