ARTICLE

Inattention, Hyperactivity, and School Performance

in a Population of School-Age Children With
Complex Congenital Heart Disease
Amanda J. Shillingford, MDa, Marianne M. Glanzman, MDb, Richard F. Ittenbach, PhDc, Robert R. Clancy, MDd, J. William Gaynor, MDe,
Gil Wernovsky, MDa
Divisions of aCardiology, bChild Development and Rehabilitation, cBiostatistics and Data Management Core, eCardiothoracic Surgery, and dNeurology, Childrens Hospital
of Philadelphia, Philadelphia, Pennsylvania
The authors have indicated they have no nancial relationships relevant to this article to disclose.

Whats Known on This Subject

What This Study Adds

Children with complex congenital heart disease are known to have neurodevelopmental impairment, particularly related to visual-spatial skills, ne motor skills, and language
development. New evidence suggests that the congenital heart disease group is also at
risk for behavioral problems.

We are the rst 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 signicant problems with inattention and hyperactivity.

ABSTRACT
INTRODUCTION. There is a growing interest in characterizing the neurodevelopmental out-

comes 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 childs 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

www.pediatrics.org/cgi/doi/10.1542/
peds.2007-1066
doi:10.1542/peds.2007-1066
Key Words
congenital heart disease, ADHD, congenital
heart disease outcomes, school performance,
deep hypothermic circulatory arrest
Abbreviations
CHD congenital heart disease
CPB cardiopulmonary bypass
DHCA deep hypothermic circulatory arrest
BASCBehavior Assessment System for
Children
ADHD-IVAttention-Decit/Hyperactivity
Disorder Rating Scale-IV
ADHDattention-decit/hyperactivity disorder
Accepted for publication Sep 5, 2007
Address correspondence to Amanda J.
Shillingford, MD, Division of Cardiology,
Childrens Hospital of Philadelphia, 34th Street
and Civic Center Boulevard, Philadelphia, PA
19104. E-mail: shillingford@email.chop.edu

(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
PEDIATRICS (ISSN Numbers: Print, 0031-4005;
scores for inattention and hyperactivity on the Behavior Assessment System for Children
Online, 1098-4275). Copyright 2008 by the
was 3 to 4 times higher than observed in the general population. On the AttentionAmerican Academy of Pediatrics
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.

ORE THAN 10 000 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.25 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
PEDIATRICS Volume 121, Number 4, April 2008

Downloaded from pediatrics.aappublications.org at Indonesia:AAP Sponsored on May 16, 2015

e759

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.810
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 nations 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.9,1218 Recent reports have specifically identified a high prevalence of
inattention and hyperactivity behaviors in the schoolage population.9,1922 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.
METHODS
Subjects
This study was a cross-sectional analysis of patients who
were participants in the Allopurinol Neurocardiac Protection Trial, which was performed at the Childrens
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.
Inclusion Criteria
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 childs home,
which included questionnaires and rating scales to be
completed by the childs parent and teacher. Teacher
assessments were based on the entire period that he or
she served as the childs teacher. The parents were requested to give questionnaires and ratings scales to their
e760

SHILLINGFORD et al

childs teacher. Parents and teachers returned completed

forms independently to the Childrens Hospital of Philadelphia Cardiac Center.
Parents were given a General Medical Summary to
elicit general information about the childs 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 childs 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).
Scoring
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,

Downloaded from pediatrics.aappublications.org at Indonesia:AAP Sponsored on May 16, 2015

(3) school support outside of the classroom, or (4) fulltime 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.
Outcomes
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.
Statistics
Archived and newly acquired survey data obtained from
109 children participating in the Allopurinol Neuroprotection Trial at the Childrens 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
.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).
RESULTS
Patients
A total of 318 neonates who were enrolled in the Allopurinol Neurocardiac Protection Trial underwent cardiac
surgery with DHCA between 1992 and 1997.23 Fol-

low-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 childs 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 childs academic

TABLE 1 Surgical Procedures (N 109)

Variable

Data

Staged reconstruction (toward a Fontan operation), n (%)

HLHS, n
Other single ventricle, n
Arterial switch operation, n (%)
TGA/IVS, n
TGA/VSD, n
TOF repair, n (%)
TOF, n
TOF/PA, n
Repair of VSD/arch obstruction, n (%)
VSD/coarctation of aorta, n
VSD/interrupted aortic arch, n
Other , n (%)

46 (42)
23
23
29 (27)
20
9
12 (11)
7
5
11 (10)
5
6
11 (10)

HLHS indicates hypoplastic left heart syndrome; TGA, transposition of the great arteries; IVS,
intact ventricular septum; VSD, ventricular septal defect; TOF, tetralogy of Fallot; PA, pulmonary
atresia.

PEDIATRICS Volume 121, Number 4, April 2008

Downloaded from pediatrics.aappublications.org at Indonesia:AAP Sponsored on May 16, 2015

e761

TABLE 2 Teacher Ratings of Childs Academic Performance

Variable

Well Below
Average, n
(%)

At or Below
Average, n
(%)

At or Above
Average, n
(%)

Well Above
Average, n
(%)

Reading orally (n 82)

Reading comprehension (n 82)
Math calculation (n 84)
Math word problems (n 82)
Writing short stories/essays (n 74)

15 (18)
12 (15)
12 (14)
14 (17)
15 (20)

15 (18)
17 (22)
20 (24)
21 (26)
19 (26)

37 (45)
39 (37)
39 (46)
38 (46)
33 (45)

15 (18)
14 (15)
13 (15)
9 (11)
7 (9)

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.
ADHD-IV
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 highrisk scores based on teacher responses, whereas 5%
received intermediate-risk scores. For the outcome of
hyperactivity, 29% of the children received high-risk

FIGURE 1
Distribution of high-risk scores on the BASC (see text for
details). The rst column represents the percentage of
high-risk scores expected in the normal population
(healthy control subjects). The subsequent columns show
the proportion of children receiving high-risk scores for
inattention and hyperactivity as rated by parents and
teachers. For all of the categories, a statistically signicant
greater proportion of high-risk scores was given to the children with CHD compared with the expected proportion in
healthy control subjects.

% of patients at high risk

15

P < .001

10

P < .001
P = .007

P = .002

Healthy controls

e762

SHILLINGFORD et al

Inattention
(parent)

Inattention
(teacher)

Hyperactivity
(parent)

Downloaded from pediatrics.aappublications.org at Indonesia:AAP Sponsored on May 16, 2015

Hyperactivity
(teacher)

30

FIGURE 2
Distribution of high-risk scores on the ADHD-IV rating scale
(see text for details). The columns represent the proportion
of children with CHD receiving high-risk scores for inattention and hyperactivity as rated by parents and teachers.
Note that a greater proportion of children received abnormal scores from parents compared with teachers.

% of subjects at high risk

25

20

15

10

Inattention (parent)

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.

No school support
School support within classroom
School support outside classroom
Full-time special education classroom

15%

51%

13%

21%

FIGURE 3
Distribution of the type of remedial school services that the children in this cohort used.

Inattention (teacher) Hyperactivity (parent) Hyperactivity (teacher)

Perioperative Risk Factors

No statistically significant associations between perioperative variables and adverse outcomes were observed
(Table 3).
DISCUSSION
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 childs 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).810 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
PEDIATRICS Volume 121, Number 4, April 2008

Downloaded from pediatrics.aappublications.org at Indonesia:AAP Sponsored on May 16, 2015

e763

TABLE 3 Results of Risk Analysis of Perioperative Variables for

Adverse Outcomes
Variable

Inattention, Hyperactivity, Use of Remedial

P
P
School Services,
P

Preoperative
Anatomic diagnosisa
Gender
Younger gestational age
Lower birth weight
Smaller head circumference
Apgar at 1 min
Apgar at 5 min
Intraoperative
Longer-duration DHCA
Longer-duration CPB
Longer total support time
Study drug recipient
(Allopurinol)
Postoperative
Seizures
Cardiac arrest
Longer length of stay

.44
.63
.26
.07
.42
.33
.75

.21
.65
.40
.49
.82
.62
.96

.41
.36
.40
.15
.82
.29
.83

.81
.55
.88
.41

.48
.46
.09
.51

.24
.69
.30
.85

.91
.97
.38

.91
.97
.42

.23
.94
.36

a Biventricle repair without postoperative hypoxemia (acyanotic heart disease) versus single
ventricle repair leading to a Fontan operation associated with long-term hypoxemia (cyanotic
heart disease).

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.2,5,2830 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.3237 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 dextrotransposition of the great arteries.1517,32,4143 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 emphae764

SHILLINGFORD et al

sized 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

Downloaded from pediatrics.aappublications.org at Indonesia:AAP Sponsored on May 16, 2015

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 childs 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.5254 ADHD is a clinical
diagnosis that includes parent and teacher rating scales
of a childs 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 childs 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.
CONCLUSIONS
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.
ACKNOWLEDGMENT
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.
REFERENCES
1. Hoffman JI, Kaplan S. The incidence of congenital heart disease. J Am Coll Cardiol. 2002;39(12):1890 1900
2. Glauser TA, Rorke LB, Weinberg PM, Clancy RR. Congenital
brain anomalies associated with the hypoplastic left heart syndrome. Pediatrics. 1990;85(6):984 990
3. Natowicz M, Chatten J, Clancy R, et al. Genetic disorders and
major extracardiac anomalies associated with the hypoplastic
left heart syndrome. Pediatrics. 1988;82(5):698 706
4. van Houten JP, Rothman A, Bejar R. High incidence of cranial

PEDIATRICS Volume 121, Number 4, April 2008

Downloaded from pediatrics.aappublications.org at Indonesia:AAP Sponsored on May 16, 2015

e765

5.

6.

7.

8.

9.

10.

11.

12.

13.

14.

15.

16.

17.

18.

19.

20.

21.

22.

23.

ultrasound abnormalities in full-term infants with congenital

heart disease. Am J Perinatol. 1996;13(1):4753
Mahle WT, Tavani F, Zimmerman RA, et al. An MRI study of
neurological injury before and after congenital heart surgery.
Circulation. 2002;106(12 Suppl 1):I109 I114
Kirkham FJ. Recognition and prevention of neurological complications in pediatric cardiac surgery. Pediatr Cardiol. 1998;
19(4):331345
Hsia TY, Gruber PJ. Factors influencing neurologic outcome
after neonatal cardiopulmonary bypass: what we can and cannot control. Ann Thorac Surg. 2006;81(6):S2381S2388
ODougherty M, Berntson GG, Boysen ST, Wright FS, Teske D.
Psychophysiological predictors of attentional dysfunction in
children with congenital heart defects. Psychophysiology. 1988;
25(3):305315
Hovels-Gurich HH, Konrad K, Skorzenski D, HerpertzDahlmann B, Messmer BJ, Seghaye MC. Attentional dysfunction in children after corrective cardiac surgery in infancy. Ann
Thorac Surg. 2007;83(4):14251430
Rasof B, Linde LM, Dunn OJ. Intellectual development in
children with congenital heart disease. Child Dev. 1967;38(4):
10431053
Welke KF, Shen I, Ungerleider RM. Current assessment of
mortality rates in congenital cardiac surgery. Ann Thorac Surg.
2006;82(1):164 170
Limperopoulos C, Majnemer A, Shevell MI, Rosenblatt B,
Rohlicek C, Tchervenkov C. Neurodevelopmental status of
newborns and infants with congenital heart defects before and
after open heart surgery. J Pediatr. 2000;137(5):638 645
Limperopoulos C, Majnemer A, Shevell MI, et al. Functional
limitations in young children with congenital heart defects
after cardiac surgery. Pediatrics. 2001;108(6):13251331
Wernovsky G, Stiles KM, Gauvreau K, et al. Cognitive development after the Fontan operation. Circulation. 2000;102(8):
883 889
Bellinger DC, Wypij D, Kuban KC, et al. Developmental and
neurological status of children at 4 years of age after heart
surgery with hypothermic circulatory arrest or low-flow
cardiopulmonary bypass. Circulation. 1999;100(5):526 532
Bellinger DC, Wypij D, duDuplessis AJ, et al. Neurodevelopmental status at eight years in children with dextrotransposition of the great arteries: the Boston Circulatory Arrest Trial. J Thorac Cardiovasc Surg. 2003;126(5):13851396
Bellinger DC, Bernstein JH, Kirkwood MW, Rappaport LA,
Newburger JW. Visual-spatial skills in children after openheart surgery. J Dev Behav Pediatr. 2003;24(3):169 179
Wray J, Sensky T. Congenital heart disease and cardiac surgery
in childhood: effects on cognitive function and academic ability. Heart. 2001;85(6):687 691
Mahle WT, Clancy RR, Moss EM, Gerdes M, Jobes DR, Wernovsky G. Neurodevelopmental outcome and lifestyle assessment in school-aged and adolescent children with hypoplastic
left heart syndrome. Pediatrics. 2000;105(5):10821089
Kirshbom PM, Flynn TB, Clancy RR, et al. Late neurodevelopmental outcome after repair of total anomalous pulmonary
venous connection. J Thorac Cardiovasc Surg. 2005;129(5):
10911097
Dunbar-Masterson C, Wypij D, Bellinger DC, et al. General
health status of children with D-transposition of the great
arteries after the arterial switch operation. Circulation. 2001;
104(12 Suppl 1):I138 I142
Casey FA, Sykes DH, Craig BG, Power R, Mulholland HC.
Behavioral adjustment of children with surgically palliated
complex congenital heart disease. J Pediatr Psychol. 1996;21(3):
335352
Clancy RR, McGaurn SA, Goin JE, et al. Allopurinol neurocardiac protection trial in infants undergoing heart surgery using

e766

SHILLINGFORD et al

24.

25.
26.

27.

28.

29.

30.

31.

32.

33.

34.

35.

36.

37.

38.

39.

40.

41.

42.

deep hypothermic circulatory arrest. Pediatrics. 2001;108(1):

6170
Reynolds CR, Kamphaus RW. Manual for the Behavior Assessment System for Children. Circle Pines, MN: American Guidance
Council; 1992
DuPaul GJ, Powers TJ, Anastopoulos AD, Reid R. The ADHD
Rating Scale IV Manual. New York, NY: Guilford Press; 1999
Kaltman JR, Di H, Tian Z, Rychik J. Impact of congenital heart
disease on cerebrovascular blood flow dynamics in the fetus.
Ultrasound Obstet Gynecol. 2005;25(1):3236
Donofrio MT, Bremer YA, Schieken RM, et al. Autoregulation
of cerebral blood flow in fetuses with congenital heart disease:
the brain sparing effect. Pediatr Cardiol. 2003;24(5):436 443
Limperopoulos C, Majnemer A, Shevell MI, Rosenblatt B,
Rohlicek C, Tchervenkov C. Neurologic status of newborns
with congenital heart defects before open heart surgery. Pediatrics. 1999;103(2):402 408
Galli KK, Zimmerman RA, Jarvik GP, et al. Periventricular
leukomalacia is common after neonatal cardiac surgery. J Thorac Cardiovasc Surg. 2004;127(3):692704
Shillingford AJ, Ittenbach RF, Marino BS, et al. Aortic morphometry and microcephaly in hypoplastic left heart syndrome. Cardiol Young. 2007;17(2):189 195
Bass JL, Corwin M, Gozal D, et al. The effect of chronic or
intermittent hypoxia on cognition in childhood: a review of the
evidence. Pediatrics. 2004;114(3):805 816
Wypij D, Newburger JW, Rappaport LA, et al. The effect of
duration of deep hypothermic circulatory arrest in infant heart
surgery on late neurodevelopment: the Boston Circulatory
Arrest Trial. J Thorac Cardiovasc Surg. 2003;126(5):13971403
Clancy RR, McGaurn SA, Wernovsky G, et al. Risk of seizures
in survivors of newborn heart surgery using deep hypothermic
circulatory arrest. Pediatrics. 2003;111(3):592 601
Utens EM, Verhulst FC, Duivenvoorden HJ, Meijboom FJ,
Erdman RA, Hess J. Prediction of behavioural and emotional
problems in children and adolescents with operated congenital
heart disease. Eur Heart J. 1998;19(5):801 807
Goldberg CS, Bove EL, Devaney EJ, et al. A randomized clinical
trial of regional cerebral perfusion versus deep hypothermic
circulatory arrest: outcomes for infants with functional single
ventricle. J Thorac Cardiovasc Surg. 2007;133(4):880 887
Visconti KJ, Rimmer D, Gauvreau K, et al. Regional low-flow
perfusion versus circulatory arrest in neonates: one-year neurodevelopmental outcome. Ann Thorac Surg. 2006;82(6):
22072211
Gaynor JW, Wernovsky G, Jarvik GP, et al. Patient characteristics are important determinants of neurodevelopmental outcome at one year of age after neonatal and infant cardiac
surgery. J Thorac Cardiovasc Surg. 2007;133(5):1344 1353
Caldas JC, Pais-Ribeiro JL, Carneiro SR. General anesthesia,
surgery and hospitalization in children and their effects upon
cognitive, academic, emotional and sociobehavioral development - a review. Paediatr Anaesth. 2004;14(11):910 915
Forbess JM, Visconti KJ, Hancock-Friesen C, Howe RC, Bellinger DC, Jonas RA. Neurodevelopmental outcome after congenital heart surgery: results from an institutional registry.
Circulation. 2002;106(12 Suppl 1):I95I102
Goldberg CS, Schwartz EM, Brunberg JA, et al. Neurodevelopmental outcome of patients after the Fontan operation: a
comparison between children with hypoplastic left heart syndrome and other functional single ventricle lesions. J Pediatr.
2000;137(5):646 652
Newburger JW, Jonas RA, Wernovsky G, et al. A comparison
of the perioperative neurologic effects of hypothermic circulatory arrest versus low-flow cardiopulmonary bypass in infant
heart surgery. N Engl J Med. 1993;329(15):10571064
Bellinger DC, Jonas RA, Rappaport LA, et al. Developmental

Downloaded from pediatrics.aappublications.org at Indonesia:AAP Sponsored on May 16, 2015

43.

44.

45.

46.

47.

48.

49.

and neurologic status of children after heart surgery with hypothermic circulatory arrest or low-flow cardiopulmonary bypass. N Engl J Med. 1995;332(9):549 555
Rappaport LA, Wypij D, Bellinger DC, et al. Relation of seizures
after cardiac surgery in early infancy to neurodevelopmental
outcome. Boston Circulatory Arrest Study Group. Circulation.
1998;97(8):773779
Uzark K, Lincoln A, Lamberti JJ, Mainwaring RD, Spicer RL,
Moore JW. Neurodevelopmental outcomes in children with
Fontan repair of functional single ventricle. Pediatrics. 1998;
101(4 pt 1):630 633
Brosig CL, Mussatto KA, Kuhn EM, Tweddell JS. Neurodevelopmental outcome in preschool survivors of complex congenital heart disease: implications for clinical practice. J Pediatr
Health Care. 2007;21(1):312
Mahle WT, Wernovsky G. Neurodevelopmental outcomes in
hypoplastic left heart syndrome. Semin Thorac Cardiovasc Surg
Pediatr Card Surg Annu. 2004;7:39 47
Achenbach TM, Ruffle TM. The Child Behavior Checklist and
related forms for assessing behavioral/emotional problems and
competencies. Pediatr Rev. 2000;21(8):265271
Kirshbom PM, Myung RJ, Gaynor JW, et al. Preoperative
pulmonary venous obstruction affects long-term outcome for
survivors of total anomalous pulmonary venous connection
repair. Ann Thorac Surg. 2002;74(5):1616 1620
Fan J, McCandliss BD, Sommer T, Raz A, Posner MI. Testing

50.

51.

52.

53.

54.

55.

56.

the efficiency and independence of attentional networks. J

Cogn Neurosci. 2002;14(3):340 347
Gothelf D, Presburger G, Levy D, et al. Genetic, developmental,
and physical factors associated with attention deficit hyperactivity disorder in patients with velocardiofacial syndrome. Am J
Med Genet B Neuropsychiatr Genet. 2004;126(1):116 121
Pinto-Martin J, Whitaker A, Feldman J, et al. Special education
services and school performance in a regional cohort of lowbirthweight infants at age nine. Paediatr Perinat Epidemiol. 2004;
18(2):120 129
Dey AN, Bloom B. Summary health statistics for U.S. children:
National Health Interview Survey, 2003. Vital Health Stat 10.
2005;(223):178
Wolraich ML, Wibbelsman CJ, Brown TE, et al. Attentiondeficit/hyperactivity disorder among adolescents: a review of
the diagnosis, treatment, and clinical implications. Pediatrics.
2005;115(6):1734 1746
Herman KC, Lambert SF, Ialongo NS, Ostrander R. Academic
pathways between attention problems and depressive symptoms among urban African American children. J Abnorm Child
Psychol. 2007;35(2):265274
Daliento L, Mapelli D, Volpe B. Measurement of cognitive
outcome and quality of life in congenital heart disease. Heart.
2006;92(4):569 574
Biederman J. Attention-deficit/hyperactivity disorder: a selective overview. Biol Psychiatry. 2005;57(11):12151220

PEDIATRICS Volume 121, Number 4, April 2008

Downloaded from pediatrics.aappublications.org at Indonesia:AAP Sponsored on May 16, 2015

e767

Inattention, Hyperactivity, and School Performance in a Population of

School-Age Children With Complex Congenital Heart Disease
Amanda J. Shillingford, Marianne M. Glanzman, Richard F. Ittenbach, Robert R.
Clancy, J. William Gaynor and Gil Wernovsky
Pediatrics 2008;121;e759
DOI: 10.1542/peds.2007-1066
Updated Information &
Services

including high resolution figures, can be found at:

http://pediatrics.aappublications.org/content/121/4/e759.full.h
tml

References

This article cites 53 articles, 18 of which can be accessed free

at:
http://pediatrics.aappublications.org/content/121/4/e759.full.h
tml#ref-list-1

Citations

This article has been cited by 14 HighWire-hosted articles:

http://pediatrics.aappublications.org/content/121/4/e759.full.h
tml#related-urls

Subspecialty Collections

This article, along with others on similar topics, appears in

the following collection(s):
Developmental/Behavioral Issues
http://pediatrics.aappublications.org/cgi/collection/developme
nt:behavioral_issues_sub
Attention-Deficit/Hyperactivity Disorder (ADHD)
http://pediatrics.aappublications.org/cgi/collection/attention-d
eficit:hyperactivity_disorder_adhd_sub
Cardiology
http://pediatrics.aappublications.org/cgi/collection/cardiology
_sub

Permissions & Licensing

Information about reproducing this article in parts (figures,

tables) or in its entirety can be found online at:
http://pediatrics.aappublications.org/site/misc/Permissions.xht
ml

Reprints

Information about ordering reprints can be found online:

http://pediatrics.aappublications.org/site/misc/reprints.xhtml

PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

publication, it has been published continuously since 1948. PEDIATRICS is owned, published,
and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk
Grove Village, Illinois, 60007. Copyright 2008 by the American Academy of Pediatrics. All
rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

Downloaded from pediatrics.aappublications.org at Indonesia:AAP Sponsored on May 16, 2015

Inattention, Hyperactivity, and School Performance in a Population of

School-Age Children With Complex Congenital Heart Disease
Amanda J. Shillingford, Marianne M. Glanzman, Richard F. Ittenbach, Robert R.
Clancy, J. William Gaynor and Gil Wernovsky
Pediatrics 2008;121;e759
DOI: 10.1542/peds.2007-1066

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pediatrics.aappublications.org/content/121/4/e759.full.html

PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

publication, it has been published continuously since 1948. PEDIATRICS is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright 2008 by the American Academy
of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

Downloaded from pediatrics.aappublications.org at Indonesia:AAP Sponsored on May 16, 2015