INTRODUCTION. There is a growing interest in characterizing the neurodevelopmental outcomes of school-age survivors of cardiac surgery. The purpose of this study was to examine a population of 5- to 10-year-old children who underwent newborn cardiac surgery for complex congenital heart disease to characterize and assess risk factors for problems with inattention and hyperactivity, as well as the use of remedial school services.
PATIENTS AND METHODS. This study was a cross-sectional analysis of patients who underwent newborn cardiac surgery and were enrolled in a neuroprotection trial conducted at our institution between 1992 and 1997. Parents and teachers completed questionnaires for the school-age child to elicit information pertaining to the child's general health and academic performance. The severity of hyperactivity and inattention were assessed by using 2 standardized questionnaires (Attention-Deficit/Hyperactivity Disorder Rating Scale-IV and Behavior Assessment System for Children). In addition to calculating descriptive estimates of their occurrence, single-covariate logistic regression models were specified and tested by using 3 different outcomes (inattention, hyperactivity, and use of remedial school services) and 14 different covariates representing preoperative, intraoperative, and postoperative factors.
RESULTS. Data were obtained from parents and/or teachers for 109 children. Fifty-three (49%) were receiving some form of remedial academic services, and 15% were assigned to a special-education classroom. The number of children receiving clinically significant scores for inattention and hyperactivity on the Behavior Assessment System for Children was 3 to 4 times higher than observed in the general population. On the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV, 30% of the parents reported high-risk scores for inattention and 29% reported high-risk scores for hyperactivity. No perioperative factors were statistically associated with adverse outcomes.
CONCLUSION. In this cohort of children with complex congenital heart disease, a significant proportion of the children were at risk for inattention and hyperactivity, and nearly half were using remedial school services. We did not identify any perioperative risk factors, which correlated with high-risk scores or the use of remedial school services. Ongoing neurodevelopmental follow-up and screening are recommended in this vulnerable population.
- congenital heart disease
- congenital heart disease outcomes
- school performance
- deep hypothermic circulatory arrest
More than 10000 infants are born each year in the United States with a severe form of congenital heart disease (CHD) that will require a surgical procedure in the first year of life.1 These children are at risk for neurologic impairment because of a variety of reasons. The preoperative factors that have been implicated include chromosomal abnormalities and genetic syndromes, congenital central nervous system anomalies, and extracardiac anomalies, as well as acidosis and intraventricular hemorrhages resulting from unrecognized or uncontrolled physiologic alterations.2–5 Intraoperative factors, such as the effects of hypoxia-ischemia/reperfusion injury during cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA), have also been linked to poor neurologic outcome.6,7 In addition, the association of prolonged hypoxemia with cognitive delay and attention problems has long been recognized and confirmed with newer reports in patients with CHD.8–10
Surgical morbidity and mortality have improved dramatically in the past 3 decades.11 As a result, an increasing number of survivors of infant cardiac surgery are entering the nation's schools. Several studies have shown that cognitive function for the school-age CHD population as a group is within the reference range, but these children are at risk for deficits in visual-spatial and visual-motor skills, as well as impairment of speech, language, and executive functioning.9,12–18 Recent reports have specifically identified a high prevalence of inattention and hyperactivity behaviors in the school-age population.9,19–22 However, most published reports are based on a relatively small group of patients or have focused on a single cardiac lesion. In addition, no studies have used input from teachers in conjunction with the parents to assess school performance.
The primary purpose of this study was to characterize problems with inattention and hyperactivity in a group of school-age survivors of newborn cardiac surgery, as well as to obtain information about their use of remedial school services. The secondary purpose was to identify perioperative risk factors for adverse outcomes.
This study was a cross-sectional analysis of patients who were participants in the Allopurinol Neurocardiac Protection Trial, which was performed at the Children's Hospital of Philadelphia between 1992 and 1997. The details of this study have been described elsewhere.23 Infants with known lethal genetic disorders, multiple congenital anomalies, or evidence of end-organ damage identified preoperatively were excluded from the Allopurinol Neurocardiac Protection Trial. Each patient underwent cardiac surgery before 45 weeks postconception age with planned DHCA and CPB. A detailed perioperative database was maintained for this cohort up to 6 weeks postoperatively, although longer term follow-up was limited.
Between November 2002 and April 2003, parents of subjects who participated in the Allopurinol Neurocardiac Protection Trial were contacted by telephone using the demographic information available from hospital databases. Children living outside of the United States or with non-English-speaking parents were excluded from participation.
Questionnaires and Rating Scales
A packet of materials was sent to the child's home, which included questionnaires and rating scales to be completed by the child's parent and teacher. Teacher assessments were based on the entire period that he or she served as the child's teacher. The parents were requested to give questionnaires and ratings scales to their child's teacher. Parents and teachers returned completed forms independently to the Children's Hospital of Philadelphia Cardiac Center.
Parents were given a General Medical Summary to elicit general information about the child's developmental history. This survey contained questions pertaining to the special neurologic and developmental services used by the child. Parents were also asked to report whether the child had difficulty in school, received remedial educational services, or had repeated a grade. In addition, parents were requested to provide a summary of major medical and surgical events. Teachers were given an Academic Performance Summary to elicit information about the child's performance in reading, writing, and mathematics compared with other students in the classroom. Teachers were also asked to provide information about specific remedial school services provided to the child.
Parents and teachers were given the Behavior Assessment System for Children (BASC), which is a broadband rating scale used to assess a variety of childhood behaviors and emotions, including specific measures for hyperactivity and inattention that were targeted for this investigation.24 The BASC has been standardized in the general population with published normative data. The validated computerized scoring system designates scores ≥2 SDs above the population mean as “clinically significant” and scores falling between 1 and 2 SDs above the population mean as “at risk” for problems within a measured category. Parents and teachers were also given the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-IV), which is designed to quantify symptoms of attention-deficit/hyperactivity disorder (ADHD) as described in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. This tool also enables the measurement of inattention and hyperactivity separately.25 The ADHD-IV was validated in a population of school children who were referred for a formal evaluation of ADHD based on teachers' concerns for behavior problems. Scores greater than or equal to the 85th percentile were considered “clinically significant,” and threshold scores are available for predicting a diagnosis of ADHD or ruling out a diagnosis of ADHD subtypes. Scoring systems for both the BASC and ADHD-IV are based on gender, age, and rater (parent or teacher).
In the present study, patients were classified according to scores received on the rating scales. For the BASC, scores of ≥2 SDs were classified into a group considered “high risk” for functionally impairing problems with inattention or hyperactivity. Scores falling between 1 and 2 SDs were classified as “intermediate risk,” whereas scores of <1 SD were classified as “low risk.” Similarly, scores on the ADHD-IV for inattention and hyperactivity were classified into high-risk (≥85th percentile), intermediate-risk (80–84th percentile), and low-risk (<80th percentile) groups. Based on responses from the teacher and/or parent, the children were categorized according to their use of remedial school services as follows: (1) no school support, (2) school support within the classroom, (3) school support outside of the classroom, or (4) full-time special education classroom. School support was defined as the provision of additional educational services in math or reading. Group 1 was considered low risk, whereas groups 2 through 4 were considered high risk. For the purpose of this study, isolated speech and language intervention was not considered a special service, because it often (although not always) is an intervention for pronunciation alone.
The primary outcomes included high-risk scores for inattention and hyperactivity on either the BASC or ADHD-IV from the teacher and/or parent, as well as the use of remedial school services. For risk analysis of adverse primary outcomes, the identified perioperative variables included anatomic diagnosis designated as biventricle physiology (acyanotic CHD) versus single ventricle physiology (cyanotic CHD), gender, gestational age, head circumference, low birth weight, Apgar scores at 1 and 5 minutes, DHCA, CPB, total cardiac support time, study drug (Allopurinol, Burroughs Wellcome Company, Research Triangle Park, NC) recipient, postoperative seizure, postoperative cardiac arrest, and length of stay. Children receiving high-risk scores were compared with those who received low-risk scores for each of the outcomes of inattention, hyperactivity, and the use of remedial services.
Archived and newly acquired survey data obtained from 109 children participating in the Allopurinol Neuroprotection Trial at the Children's Hospital of Philadelphia between 1992 and 1997 served as the basis for this study. Data analysis involved 3 distinct phases. Phase 1 consisted of generating simple descriptive statistics for all of the variables in the data set for the entire sample. Phase 2 consisted of calculating the proportion of children receiving abnormal scores for inattention and hyperactivity on the ADHD-IV or BASC, as well as the proportion of children receiving various levels of remedial school support. One sample test of proportions was used to compare the distribution of clinically significant scores between our cohort and the population norms. Finally, in phase 3, the model testing phase of the study, 14 different logistic regression models were specified and tested for 3 of the aforementioned outcomes (inattention, hyperactivity, and use of remedial school services) using a combination of preoperative, perioperative, and postoperative variables. The experiment-wise error rate for all of the analyses tested were held constant at the α = .05 level across models because of the secondary nature of the analyses. All of the data were analyzed using Stata 9.1 (SAS Institute, Inc, Cary, NC).
A total of 318 neonates who were enrolled in the Allopurinol Neurocardiac Protection Trial underwent cardiac surgery with DHCA between 1992 and 1997.23 Follow-up for research purposes was limited for 260 early postoperative survivors after the study completed. Three international children were excluded from the present study. A total of 164 families were contacted by telephone and invited to participate in this study. The 93 remaining children could not be located by using the available resources. Of those contacted, 15 children were deceased, and 3 families were excluded because of language barriers. One parent declined participation. Packets were sent to 145 families who agreed to participate in the study. Responses were received for 109 children (75%). For 76 children (52%), responses to questionnaires were received from both the teacher and the parent. For 13 children, responses to questionnaires were received from the child's parent only. For 20 children, responses to questionnaires were received from the teacher only. Neither parent nor teacher questionnaire responses were received for 36 children.
The mean age of the cohort at the time of questionnaire completion was 7.9 ± 1.5 years (range: 5.4–10.4 years), and 67% of the children were boys. There was no significant difference in the prevalence of attention and hyperactivity problems among the different age groups. The majority of the children were identified as white (86%) at birth, and 8% were identified as black. In addition, there were no significant differences in perioperative clinical characteristics between the 109 participants in this study and the nondeceased patients who were initially enrolled in the Allopurinol Neurocardiac Protection Trial but not included in this study because either no responses were received or the patient could not be located. The types of CHD represented in this cohort are shown in Table 1. Of note, 42% of the participants underwent a Fontan operation, which involves at least 2 major surgical procedures that occur during the first few years of life.
General Medical Summary and Academic Performance Summary
Based on parent reports, 18% of the children had repeated a grade. Teacher reports of the child's academic performance are shown in Table 2. In ≥1 subject area, 14% to 20% of the children were considered to perform “well below average.” A comparable proportion was reported to be performing above average in all areas, except for writing short stories or essays, in which 20% of the children were rated well below average, whereas only 9% were rated above average. For reading comprehension and oral reading, the majority of the children performing “below average” received abnormal scores for inattention (59%) and hyperactivity (56%) compared with the group who were considered “average or above average,” in whom abnormal scores for inattention (39%) and hyperactivity (23%) were less. Similarly, for mathematical calculation and word problems, the majority of children received abnormal scores for inattention (68%) and hyperactivity (60%) in contrast to the group ranked as “average or above average,” in whom abnormal scores for inattention (33%) and hyperactivity (27%) occurred less. In total, 37% of the children were receiving supplemental help for reading, whereas 26% were receiving supplemental help for math.
Behavior Assessment System for Children
Completed BASC forms were received from 89 parents and 90 teachers. For the outcome of inattention, 11% of children were classified as high risk based on parent responses, and 17% received intermediate-risk scores. Teacher ratings for inattention resulted in high-risk scores for 8% of the children and intermediate-risk scores for 20% of the children. For the outcome of hyperactivity, 10% of the children were classified as high risk based on parent responses, whereas another 10% received intermediate-risk scores. Teacher ratings for hyperactivity resulted in high-risk scores for 8% of the children and intermediate-risk scores for 12% of the children. Using the standardized BASC scoring system, ∼2.5% of the general population should have a score that is >2 SDs above the population mean. Therefore, the number of children receiving high-risk scores for inattention and hyperactivity in this sample is 3 to 4 times greater than observed in the general population and represents a statistically significant difference, as shown in Fig 1. Completed BASC forms from both a parent and teacher were received for 71 children, and 10 (14%) of these children received abnormal scores from both raters for inattention whereas, 9 (13%) received abnormal scores from both raters for hyperactivity. Six (5.5%) children received abnormal scores from both raters for inattention and hyperactivity.
Completed ADHD-IV scales were received from 89 parents and 93 teachers. For the outcome of inattention, 30% of the children received high-risk scores based on parent responses, and 5% received intermediate risk scores. In contrast, 10% of the children received high-risk scores based on teacher responses, whereas 5% received intermediate-risk scores. For the outcome of hyperactivity, 29% of the children received high-risk scores based on parent responses, and no scores fell into the intermediate risk category. Based on teachers' responses, 12% of the children received high-risk scores, whereas 5% received intermediate-risk scores. The distribution of high-risk scores is shown in Fig 2. Using the recommended threshold scores for the ADHD-IV tool, 80% of the cohort would be unlikely to have ADHD.25 However, 5% would be highly likely to have ADHD, and another 15% would be considered at risk for having a diagnosis of ADHD.
Remedial School Services
In this cohort of children, approximately half are in a regular classroom full time and not receiving additional services (Fig 3). A total of 15% of the cohort have already been placed into a full-time special education classroom. Of the remaining group, 21% of the children were receiving remedial help in math and/or reading within the classroom and 13% of the children were removed from the classroom for remedial help in math and/or reading.
Perioperative Risk Factors
No statistically significant associations between perioperative variables and adverse outcomes were observed (Table 3).
In this cross-sectional study of early school-age children with complex CHD who underwent cardiac surgery with DHCA before 2 months of age, we found that a significant proportion of the children received high-risk scores for inattention and hyperactivity based on standardized questionnaire data. In addition, nearly half of the cohort was receiving some form of remedial services in the school, including 15% who had already been placed into a full-time special education classroom. To our knowledge, this study is the first report to use both parent and teacher input to assess a child's risk for problems with inattention and hyperactivity, as well as to assess the level of school support provided to an individual child.
We were unable to identify statistically significant associations between any of the targeted preoperative, intraoperative, and postoperative variables and high-risk scores for inattention and hyperactivity or the need for remedial school services within the classroom. In contrast to previous reports, we did not see an association between abnormal scores and postoperative hypoxemia (“cyanotic CHD”).8–10 There were no statistically significant differences between the children with a Fontan operation for single ventricle and those who underwent biventricular repair, nor were there associations between adverse outcomes and the duration of intraoperative support, such as CPB and DHCA. However, the sample size for this study was suboptimally powered, and, therefore, it is possible that risk factors could be identified in a larger sample.
Infants born with severe forms of CHD are subject to numerous physical stressors and abnormal physiologic states, with additive effects from fetal life through school age. In the fetus with CHD, cerebral oxygen delivery may be abnormal because of changes in cerebral blood flow, oxygen content, or both.26,27 Moreover, central nervous system abnormalities, such as microcephaly and periventricular leukomalacia, have been described in infants with CHD before cardiac surgery.2,5,28–30 In patients without CHD, a relationship between chronic hypoxia and abnormal neurologic outcomes, particularly related to behavior and school performance, has been described. 31 In addition, the effects of CPB and DHCA and related sequelae, such as reperfusion injury and embolic events on neurologic outcomes, are inconclusive, but several studies have indicated that prolonged periods of CPB, DHCA, or both may be associated with an increased risk of neurologic compromise.32–37 The potential adverse effects of prolonged anesthesia and sedation or multiple procedures and hospitalizations may also affect the neurodevelopmental status and psychological status of children who have undergone infant heart surgery.34,38 Other important considerations include socioeconomic status and parental IQ, which have been strongly correlated with neurologic and developmental outcomes.14,39,40
Our findings are consistent with those from the Boston Circulatory Arrest Study, which prospectively followed a homogeneous cohort of infants with dextro-transposition of the great arteries.15–17,32,41–43 The 8-year findings have been reported and show that the cohort demonstrated an increased incidence of deficits in motor function, visual motor integration, and executive functioning. Similar to our report, one-third of the children were receiving school support, and 10% of the children had already repeated a grade.16 In general, this group of children had IQ scores that were within the reference range, but the mean scores as a group were lower compared with the general population. It should be emphasized that, in contrast to the Boston Circulatory Arrest Study, our study was composed of a heterogenous population including a wide range of CHD. We did not control for the numbers of operations and hospitalizations, which have been associated with behavior problems and impaired quality of life.34
In reports of children with various forms of single ventricle, most children have cognitive abilities that are measured within the reference range. However, mean scores as a group are lower compared with the population.14,40,44,45 Below-average scores on infant neurodevelopmental evaluations have been reported in patients with hypoplastic left heart syndrome after stage 1 Norwood surgeries.35,36 Mahle et al46 reported the school-age follow-up in a group of children with hypoplastic left heart syndrome and found that 34% were receiving special services in school. Of the 28 children who underwent more comprehensive evaluations and who had parents complete the Achenbach Child Behavior Checklist,47 18% received concerning scores for attention problems. In addition, 67% of the children demonstrated evidence of ADHD based on history and physical examination by a neurologist.46
Attention issues were similarly reported in a group of school-age children who underwent infant repair of total anomalous pulmonary venous connection. Parental reports revealed that 27% of the children were in special education classes or had repeated a grade.48 A subset of this group underwent more comprehensive neurologic evaluation.20 In contrast to our findings, there were no significant differences in parental reports of inattention in the BASC group as compared with the general population. However, direct tests of sustained attention and complex attention were below average. In addition, examination by a neurologist revealed that 47% exhibited abnormal inattentiveness and 27% demonstrated abnormal hyperactivity.20
A recent report from Hovels-Gurich et al9 studied a population of children with CHD using the Attention Network Test, which is an interactive tool that assesses 3 functionally defined attentional networks in the brain.49 Patients who underwent surgical repair of tetralogy of Fallot or isolated ventricular septal defect were compared with healthy control subjects. The authors found that the tetralogy of Fallot group, representing children who were hypoxemic (cyanotic) in infancy, demonstrated poor attention skills with respect to executive functioning as compared with the ventricular septal defect group and healthy control subjects, who were not hypoxemic (acyanotic). Although the sample size is relatively small, the authors provided compelling data to support our findings that survivors of cardiac surgery for complex CHD are at risk for attention problems.
In patients with velocardiofacial syndrome or microdeletion of chromosome 22q11, in whom CHD is common, the prevalence of ADHD has been reported to be as high as 42%.50 Likewise, school-age follow-up of children who were born preterm and with low birth weight has demonstrated that nearly one third are in a special education classroom, and scores for abnormal hyperactivity are twice as common as expected in the general population.51 There are similarities between these populations, because the patients with velocardiofacial syndrome can have critical forms of CHD, and the preterm and low-birth weight populations may experience similar physiologic alterations, including cerebral ischemia and/or hemorrhage during the early postnatal period. Determining the relative contributions of social factors, genetic factors, and physiologic disturbances in the developing brain remains an important area of investigation.
In the present study, nearly one third of the children received elevated scores on the ADHD-IV from parents, whereas only ∼15% of the children received abnormal scores from the teachers. On the BASC as well, parent reports identified more children with abnormal scores compared with teachers. The reason for this discrepancy is unclear but may be related to teachers having a higher threshold for considering the behaviors of a child with chronic disease to be abnormal. In addition, 15% of the teachers were comparing the children with the other students in a special education classroom, a setting in which behavior and developmental problems are prevalent. Thus, the behaviors of the children in our study may have been less noticeable to the teacher, whereas the parents are likely to be comparing their child to the general population. For the purpose of this study, the criteria for designating a child's score on the ADHD-IV were conservative, and, therefore, the clinical significance of abnormal scores may be underestimated. In other words, children with borderline scores who were classified in the low-risk category may have actually had clinically important symptoms if a more comprehensive evaluation was performed.
The prevalence of ADHD in the pediatric population is estimated to be between 5% and 10% and is associated with significant comorbidities, which can include anxiety disorders, depression, social problems, conduct disorders, and learning disabilities.52–54 ADHD is a clinical diagnosis that includes parent and teacher rating scales of a child's behavior, as well as structured diagnostic interviews and an evaluation to rule out other causes for the symptoms. Although conclusions about the prevalence of ADHD in the CHD population cannot be made based on the current study, our findings do suggest that the risk for attention and hyperactivity problems is an important consideration in CHD survivors. Formal cognitive testing was not performed in this population to delineate a relationship between impaired cognition and risk for inattention and hyperactivity. However, our data do suggest a link between poor performance in math and reading skills and abnormal scores for inattention and hyperactivity.
Rating scales are most useful as a screening tool or in conjunction with structured interviews. To further characterize the prevalence of clinically important ADHD, comprehensive diagnostic evaluations will be helpful in this population. ADHD, if untreated, can be a barrier for success in school or work and can affect the quality of life of this population as the children progress through the teenage years and into adulthood.54 Importantly, it is unclear whether medical therapies commonly used for ADHD treatment are helpful in the CHD population. Quality of life in survivors of CHD may be affected by their medical condition alone, and the risk of ADHD may further adversely impact the individual.55
The present report is somewhat limited, because the children had not been followed prospectively after the initial operation. Parental reports about the child's interim medical history were incomplete, and, therefore, variables such as the number of hospitalizations and surgical procedures could not be included in the analyses. Although infants with identifiable lethal genetic abnormalities were excluded from enrollment in the Allopurinol Neurocardiac Protection Trial, children with genetic conditions associated with more subtle features may not have been recognized in the neonatal period. Therefore, we cannot exclude the possibility that some of the children in our cohort may have undiagnosed syndromes that are independently associated with an increased risk of behavior problems. The socioeconomic status of each child and detailed family histories were not available, which is relevant, because ADHD is known to have high heritability.56 Moreover, the status of almost half of the original cohort was unknown, and presumably a portion of this group included deceased patients. Only 1 patient declined participation in this study during the initial telephone contact, but questionnaires were not returned from all of the teachers and parents. Finally, although we have identified a population at risk for attention and hyperactivity problems, a clinical diagnosis of ADHD requires the use of rating scales in conjunction with a direct interview and clinical examination.
We conclude that children with complex CHD who required cardiac surgery in early infancy are at risk for attention and hyperactivity problems, including ADHD. We have also shown that nearly half of the school-age survivors are using remedial resources within the schools. Formal evaluation for ADHD symptoms in larger cohorts is necessary to assess prevalence and risk factors in this vulnerable cardiac population, as well as the safety and efficacy of medical therapies.
The Allopurinol Neurocardiac Protection Trial was funded by a grant from the National Institute for Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.
- Accepted September 5, 2007.
- Address correspondence to Amanda J. Shillingford, MD, Division of Cardiology, Children's Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104. E-mail:
The authors have indicated they have no financial relationships relevant to this article to disclose.
What's Known on This Subject
Children with complex congenital heart disease are known to have neurodevelopmental impairment, particularly related to visual-spatial skills, fine motor skills, and language development. New evidence suggests that the congenital heart disease group is also at risk for behavioral problems.
What This Study Adds
We are the first to use standardized questionnaire data from both parents and teachers to identify a high prevalence of children with congenital heart disease who are at risk for clinically significant problems with inattention and hyperactivity.
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