Journal of Pediatric Psychology, Vol. 25, No. 8, 2000, pp. 567-576
© 2000 Society of Pediatric Psychology
Review |
Cognitive and Psychological Outcomes in Pediatric Heart Transplantation
University of Florida College of Health Professions
All correspondence should be sent to John F. Tadaro, Brown University School of Medicine, Department of Psychiatry and Human Behavior, The Miriam Hospital/Rise Building, Center for Behavioral and Preventive Medicine, Providence, Rhode Island 02906. E-mail: John_Todaro{at}brown.edu .
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Abstract |
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Objective: To review empirical literature investigating the cognitive and psychological effects of pediatric heart transplantation.
Methods: Electronic and library searches were used to identify empirical studies examining the cognitive and psychological effects of pediatric heart transplantation. Only studies investigating cognitive or psychological outcomes, either prospectively or cross-sectionally, were reviewed.
Results: Preliminary findings suggest that children and adolescents generally functioned within the normal range on most measures of cognitive functioning post-transplant. However, a complicated transplant course caused by infections or rejections may place these recipients at increased risk for cognitive difficulties post-transplant. Studies also suggested that approximately 20%-24% of pediatric heart transplant recipients experienced significant symptoms of psychological distress (e.g., anxiety, depression, behavior problems) during the first year post-transplant.
Conclusions: Research suggests that some recipients are at risk for cognitive and psychological difficulties post-transplant and may require additional academic remediation and/or psychological intervention to address these challenges. Given the limited number of empirical studies available at this time, continued research investigating cognitive and psychological outcomes following pediatric heart transplantation is needed.
Key words: pediatric heart transplant; cognitive functioning; psychological functioning; transplant outcomes.
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Introduction |
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Heart transplantation has become the treatment of choice for children and adolescents with end stage heart disease. According to the Registry of the International Society of Heart and Lung Transplantation, approximately 3,500 pediatric heart transplants have been performed worldwide since 1982 (Boucek et al., 1997
). Medical
improvements in heart transplantation have yielded overall 1-year survival
rates of 75% to 85% (Boucek et al.,
1997; Shaddy et al.,
1996) and 4-year survival rates of 60% to 65%
(Hosenpud, Bennett, Keck, Fiol, &
Novick, 1997) in children and adolescents. To date, however, much
of the heart transplantation literature has focused on adult patients.
Although research examining medical outcomes in pediatric heart
transplantation is beginning to move forward, relatively few studies have
examined the cognitive and psychological impact of transplantation in children
and adolescents.
Pediatric heart disease must be conceptualized differently than heart
disease in adults due to the differing etiologies of children's heart disease.
In adults, the most common cause of heart disease is coronary artery disease
secondary to artherosclerotic processes. In children and adolescents, however,
the most common etiologies for coronary illness are congenital heart disease
due to malformations of the cardiovascular system or cardiomyopathy
(Baron, Fennell, & Voeller,
1995). In most cases, open and closed heart surgeries are
performed to correct these malformations.
Researchers have investigated the cognitive effects of pediatric open-heart
surgery. Cognitive outcomes following open-heart surgery have suggested that
longer duration of hypoxic states secondary to chronic heart disease
(Aram, Ekelman, Ben-Schachar, &
Levinsohn, 1985; Newburger,
Silbert, Buckley, & Flyer, 1984;
O'Dougherty, Wright, Levenson, &
Torres, 1985), deep hypothermic arrest procedures (Bellinger et
al., 1995; Miller, Mamourian, Tesman,
& Baylen, 1994), and longer duration on the cardiopulmonary
bypass pump (Branthwaite, 1972;
Dickson & Sambrooks, 1979)
were associated with greater cognitive and developmental delays. All of these
risk factors share the fact that decreased oxygenation, either during the
course of chronic heart disease or secondary to surgical repair procedures,
increases the probability that children and adolescents will experience
cognitive and developmental deficits.
Psychological outcomes following pediatric open-heart surgery have also
been investigated. These studies have reported that pediatric open-heart
surgery recipients may be at greater risk for developing psychological
difficulties post-surgery than same age healthy peers
(Casey, Sykes, Craig, Power, &
Mullholland, 1996; Utens et
al., 1993). These difficulties included both internalizing and
externalizing disorders and may, ultimately, interfere with normal academic
and social development. However, relatively few studies have examined the
psychological functioning of pediatric open-heart surgery recipients, which
limits our ability to draw definitive conclusions.
Given that open-heart surgery and transplant recipients experience similar
disease etiologies and undergo, to some extent, similar medical and surgical
procedures, pediatric heart transplant recipients may experience similar
cognitive and psychological difficulties. Moreover, the course of
transplantation, including the diagnosis and decision-making stage, the
waiting period, transplantation and hospitalization stage, and the follow-up
and recovery periods (Greene & Sears,
1994; Kuhn, Davis, &
Lippman, 1988), may subject children and adolescents to additional
stressors more problematic than those experienced by open-heart surgery
recipients. The primary goal of this review, therefore, is to summarize the
current research pertaining to cognitive and psychological outcomes in
pediatric heart transplantation. This review begins with a discussion
regarding the cognitive and psychological functioning of pediatric heart
transplant recipients. Suggestions for future research pertaining to the
cognitive and psychological impact of pediatric heart transplantation will
also be provided.
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Cognitive Functioning in Pediatric Heart Transplantation |
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The effects of heart transplantation on neuropsychological functioning in children have not been extensively studied (Table I). Wray and Yacoub (1991
), in a preliminary
report, compared the neuropsychological functioning of children receiving
heart transplantation (n = 52) to children receiving alternative
open-heart surgeries (n = 52) and to normal, healthy peers
(n = 45). Children less than 5 years of age receiving heart
transplantation performed within the average range on measures of development
using the Ruth Griffiths Developmental Scales (RGDS;
Griffiths, 1970). These
researchers noted, however, that RGDS scores for children who received
transplantation were significantly lower than those for the healthy control
group. Children older than 5 who received transplantation also demonstrated
developmental scores in the average range, despite scores being significantly
lower than both comparison groups. In addition, transplant recipients
demonstrated lower grades at school and significantly higher absentee rates
than both comparison groups. Although the finding that poorer school
performance in transplant recipients was of concern, these researchers
reported that lower academic performance may have been attributable to missing
more time at school.
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In a second report, Wray, Pot-Mees, Zeitlin, Radley-Smith, and Yacoub
(1994) examined the effects of
heart and heart-lung transplantation on development, cognitive functioning,
and behavioral status in 65 children diagnosed with various coronary
anomalies. The performance of transplant recipients was compared to children
receiving other corrective heart surgeries (n = 52) and healthy
children (n = 45). Children who received transplantation between the
ages of 0 to 4.5 years performed in the normal range on the RGDS; however, on
all of the developmental subscales, these recipients performed significantly
lower than the healthy control group. Transplant and open-heart surgery groups
did not differ on any of the measures of development. For children ranging in
age from 4.6 to 16 years of age, transplanted children demonstrated lower mean
IQ scores than both of the two reference groups as measured by the British
Abilities Scales (BAS; Elliot,
1983). Performance on measures of specific academic abilities,
including arithmetic and reading, were not statistically different from either
reference group. Notably, children who received transplantation performed
worse than the healthy group on measures of spelling achievement.
Researchers have also investigated the developmental functioning of infant
heart transplant recipients. Trimm
(1991) examined language,
audiologic, psychomotor, and mental development in 54 infant heart transplant
recipients ranging in age from 1 week to 4 months. On the Sequenced Inventory
of Communication Development (SICD;
Hedrick, Prather, & Tobin,
1984), a measure of language development, 10 out 13 infants (77%)
demonstrated normal language functioning. The remaining three children
displayed minor language delays, which were remediated successfully with
speech therapy. Likewise, the vast majority of infants (90%) had normal
Brainstem Auditory-Evoked Responses (BAER). In addition, psychomotor and
mental development, as measured by the Bayley Scales of Infant Development
(BSID; Bayley, 1969), were
assessed serially at 4, 8, 12, 18, and 30 months. Longitudinal results
indicated that infants receiving transplantation demonstrated normal
psychomotor and mental development, which appeared to be stable over the
course of 30 months. However, increased variability on the Psychomotor
Developmental Index of the BSID was associated with rejection episodes
requiring steroid medication use, suggesting that organ rejection and its
associated treatments (e.g., immunosuppressant medication) may interfere will
normal psychomotor development within the first 30 months
post-transplantation.
In summary, these studies suggest that most pediatric heart transplant recipients performed within normal limits on measures of cognitive and developmental functioning. However, pediatric heart transplant recipients who underwent a more complex transplant course secondary to post-surgical infection and/or organ rejection demonstrated signs of cognitive and/or psychomotor disturbance. These children were reported to endure additional medical treatments and longer hospital stays, which may have negatively affected their school attendance and academic performance.
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Psychological Functioning in Pediatric Heart Transplantation |
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Research examining psychosocial outcomes of children and adolescents receiving heart transplantation is also limited to a few empirical investigations (Table II). In an early study examining the quality of life of pediatric heart recipients, Lawrence and Fricker (1987
)
described the psychosocial functioning of seven children between the ages of 6
and 15 years old. Although post-operative data were not reported for all
transplant recipients, these investigators reported that all children in this
small sample were able to return to their normal lifestyles and adjusted well
to the stress of transplantation. Specifically, all children were reportedly
able to attend to self-care, return to school, and maintain pretransplant
academic performance. Furthermore, six out of eight children were able to
develop age-appropriate relationships.
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Psychiatric outcomes have also been investigated in a small sample
(n = 9) of pediatric heart transplant recipients. Although the
average time of assessment post-transplant was not reported, Shapiro and
Kornfeld (1989) found that
five out of nine recipients experienced post-transplant adjustment
difficulties characterized by anxiety, depression, and/or behavior problems
using criteria from the Diagnostic and Statistical Manual of Mental
Disorders-III-R Revised (DSM-III-R;
American Psychiatric Association,
1987). The remaining four recipients reported no major adjustment
difficulties. These investigators also reported that many family members of
heart transplant recipients exhibited some symptoms of mood disturbance,
including anxiety, depression, and anger.
More recently, researchers have examined the psychological adjustment of
recipients and their families following transplantation in a larger sample of
pediatric heart transplant recipients,
(Uzark et al., 1992).
Forty-nine pediatric heart transplant recipients and their families at five
major heart transplant centers across the United States were mailed
questionnaires assessing externalizing and internalizing disorders,
self-concept, family stress, and family coping strategies. Results gathered
from self-report data suggested that transplant recipients displayed
significantly less social competence and more behavior problems compared to a
normative population as measured by the Child Behavior Checklist (CBCL;
Achenbach & Edelbrock,
1986). Further, behavior problems in transplanted children were
significantly correlated with greater family stress and fewer family resources
for dealing with stress. In contrast to previous findings reported by Shapiro
and Kornfeld (1989), scores on
measures of self-concept and anxiety were not significantly different from
those of the normative sample. On measures of functional status, 93% of
transplant recipients over 8 years of age were attending school and
participating in extracurricular activities.
Psychological functioning of pediatric heart transplant recipients has been
reported to differ across environmental settings (i.e., home, school). Wray et
al. (1994) investigated the
behavioral functioning of children who received transplantation compared to
open heart surgery recipients and a healthy control group. In the home,
transplant recipients were reported to exhibit significant behavior problems
as measured by the Richman Behavior Checklist (RCB;
Richman & Graham, 1971)
and the Rutter Scales A and B (RSAB;
Rutter, Tizard, & Whitmore,
1970). Although the prevalence of behavior problems was not
statistically different across groups, a greater percentage of children who
received transplantation (24%) were reported to demonstrate clinically
significant levels of disordered behavior (heart surgery group = 17%, healthy
group = 6%). Of the 30% of children who received transplantation who returned
to school following transplantation, none exhibited behavior problems in the
school setting.
In another study, Demaso, Twente, Spratt, and O'Brien
(1995) examined 23 pediatric
heart transplant recipients prior to transplantation and at a 1-year follow-up
visit. Psychological functioning was measured by the Children's Global
Assessment Scale (CGAS; Shaffer et al.,
1983), a global rating (0 to 100) measuring children's overall
psychological functioning. These investigators used a cutoff score of 70 to
indicate "pathological" psychological functioning. Psychological
adjustment, as measured by the CGAS, appeared to improve at 1 year
post-transplant, with significantly fewer children functioning in the
pathological range (pre-transplant = 43.5%, post-transplant = 21.7%).
Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV;
American Psychiatric Association,
1994) criteria were also gathered pre- and post-transplantation.
Results of the pre-transplant evaluation indicated that 35% of the sample met
diagnostic criteria for Psychological Symptoms Affecting Medical Condition
with only 4% of the sample meeting these criteria at the post-transplant
evaluation. Additionally, pre-transplant evaluations revealed that 13% of the
sample met diagnostic criteria for Mood Disorders Secondary to Medical
Condition with 0% meeting criteria 1 year post-transplant. Taken together, the
results of this study suggest that the psychological functioning of many
children improved 1 year post-transplant; however, approximately 20% of
pediatric transplant recipients still demonstrated symptoms of psychological
distress, although not in the diagnostic range at follow up.
In summary, it appears that most pediatric heart transplant recipients demonstrated adequate psychological adjustment within 1 year post-transplant. This is evidenced by significantly fewer recipients meeting diagnostic criteria for psychological difficulties, exhibiting fewer symptoms of poor psychological adjustment post-transplant, and many children returning to school. It appears, however, that a proportion of pediatric heart transplant recipients experienced significant levels of poor psychological adjustment following heart transplantation compared to normal, healthy peers. Although based on only a few published studies, 20%-24% of pediatric heart transplant recipients continued to experience psychological distress and exhibit disordered behavior following transplantation. We suggest that the stressors associated with transplantation (e.g., intense medical regimens, decreased socialization with peers) may have an impact on the emotional well-being of pediatric transplant recipients, resulting in symptoms of negative affect, decreased social competence, and behavior problems. Clearly, continued research is needed to help identify risk factors leading to poorer cognitive and psychological outcomes in children who undergo heart transplantation.
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Conclusions and Future Directions for Research |
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The existing literature on cognitive outcomes following pediatric heart transplantation has indicated that most recipients appear to be functioning within normal limits when assessed post-operatively. These data are encouraging since many recipients were able to return to school and pursue additional academic goals. However, Wray and Yacoub (1991
) reported an exception
whereby pediatric heart transplant recipients demonstrated lower performance
on measures of mental development and school performance, possibly due to
higher absentee rates from school. Additionally, variability in developmental
functioning within the first 30 months post-transplantation was associated
with rejection episodes requiring additional immunosuppressant medication
(Trimm, 1991). While cognitive
functioning for most recipients appears to remain intact, children and
adolescents who experienced infections and rejections post-transplant appeared
to have been at increased risk for cognitive and academic delays, since their
disease course required additional medical management and longer
hospitalizations.
Research examining psychological functioning in pediatric heart transplant
recipients suggested that, within the first year post-transplant, the majority
of pediatric transplant recipients adjusted well to the psychological stress
of transplantation (Demaso et al.,
1995). The significant reduction in psychological distress at 1
year follow-up suggested that, with time, children and adolescents may have
been able to gather sufficient emotional resources to cope adequately with the
effects of heart transplantation. However, this is not true for all pediatric
heart transplant recipients. Although conclusive rates of poor psychological
adjustment cannot be determined from the existing research, preliminary
findings suggested that 20%-24% of pediatric heart transplant recipients are
at increased risk for developing psychological difficulties, such as anxiety,
fear, depression, and behavior problems within the first year post-transplant
(Demaso et al., 1995;
Wray et al., 1994).
These preliminary findings raise a number of implications for clinical
practice. First, the pre-transplant assessment offers health care providers an
opportunity to gather valuable baseline information pertaining to the
recipients' pre-transplant functioning. In adult heart transplant candidates,
most transplant centers utilize a clinical interview and a formal assessment
battery of self-report questionnaires to assess baseline cognitive and
psychological functioning (Levenson &
Olbrisch, 1993). We recommend that similar practices be used with
pediatric transplant populations. Four broad areas of functioning should be
assessed: (1) developmental, cognitive, and academic functioning; (2)
emotional and behavioral functioning; (3) medical compliance; and (4) quality
of life. The assessment instruments used to measure cognitive and
psychological functioning will vary depending on the age and developmental
level of the recipient. Although a comprehensive clinical interview can
provide important information regarding these domains of functioning,
standardized assessment instruments completed by heart transplant recipients
or proxy raters (e.g., parents, guardians) for those children who are too
young to complete self-report measures on their own would increase the
validity and reliability of the overall assessment. Second, given that a
proportion of pediatric heart transplant recipients are at risk for cognitive
and psychological problems, parents of these children and adolescents should
be educated on how to monitor their children's psychological status. Early
detection of poor psychological adjustment could be brought to the attention
of mental health providers to provide preventative care and limit the
exacerbation of the problem. Third, since pediatric heart transplantation
likely has a bidirectional impact on both the functioning of the child and the
family system, broader interventions simultaneously targeting children and
families are needed (Kazak,
1989). Family-based interventions focused on disease education,
preventative health care, coping strategies, and enhancing family
communication and interpersonal relationships have been used with other
disease populations (Kaslow et al.,
1997; Streisand, Rodrigue,
Houck, Graham-Pole, & Berlant, 2000). In many cases, these
family interventions could be provided during hospitalization and/or shortly
following discharge in order to maximize the adjustment of children and
families during the early stages post-transplantation.
Investigating the cognitive and psychological functioning of pediatric heart transplant recipients presents a number of challenges to researchers. First, given that few numbers of children and adolescents receive heart transplantation, most studies are limited to using small sample sizes. Multicenter studies may allow investigators to study larger groups of children and adolescents. Second, because many children undergoing heart transplantation are too young to complete self-report instruments, it may be difficult to use standardized self-report instruments with all children. In that case, it may be helpful to use proxy raters to report on behalf of the recipient regarding their emotional well-being. Third, given that pediatric heart transplant recipients can range in age from 0 months to 17 years, researchers must carefully attend to several developmental issues. For instance, the impact of delayed physical development on subsequent psychological functioning must be considered. Further, given that pediatric heart transplantation increasingly occurs during early childhood, researchers should be encouraged to examine the degree to which transplantation and lifelong immunosuppression interferes with normative developmental tasks of childhood.
Within the cognitive domain, conclusions regarding the effects of heart transplantation on cognitive functioning of children and adolescents are limited by various methodological problems, such as small sample sizes, incomplete assessment batteries, and poor control for disease type and duration. Replication studies addressing these limitation are needed to better explain the potential cognitive deficits experienced by heart transplant recipients. Furthermore, additional longitudinal investigations examining the long-term impact of pediatric heart transplantation on cognitive functioning are needed. Moreover, many domains of neuropsychological functioning have not been examined in these patients. Given the impact of cardiac dysfunction on higher brain functions, future research should utilize comprehensive neuropsychological test batteries, including measures of memory and learning, executive abilities, motor functions, and visual-perceptual skills to assess a broader range of cognitive and motor abilities. Finally, as many of these transplant recipients have been reported to have high absentee rates from school, the impact of their disease on school achievement should also be examined.
Some evidence suggests that a proportion of children and adolescents may
experience psychological difficulties, such as anxiety, depression, behavior
disorders, and poor self-concept following transplantation. Future studies
should continue to assess the prevalence of psychological difficulties in
pediatric heart transplant populations. Previous research with adult heart
transplant recipients has indicated that symptoms of anxiety and depression
are prevalent and may affect long-term outcomes, such as medical compliance
(Dew, Roth, Thompson, Kormos, &
Griffith, 1996) and quality of life
(Sears, Rodrigue, Greene, & Mills,
1995). However, in the pediatric heart transplant literature,
these issues have been relatively unexplored and require further
investigation. Studies examining positive factors influencing pediatric heart
transplant outcomes are also needed. For example, future studies could examine
the influence of positive psychological constructs such as optimism, hope, and
spirituality on pediatric transplant outcomes. In addition, we know little
about the psychological adjustment of pediatric heart transplant candidates
and families who are waiting for donor hearts to become available. Research is
needed to investigate the impact of the waiting period on candidates and their
families. Finally, the effectiveness of psychosocial interventions aimed at
assisting children, adolescents, and families in coping with the stress
associated with transplantation remains to be studied.
This literature review offers health care professionals a chalkboard full
of empirical questions pertaining to the cognitive and psychological impact of
pediatric heart transplantation. In many ways, psychosocial research with
pediatric heart transplant recipients is in its infancy compared to research
with adult recipients. Pediatric researchers, however, may glean research
questions and methodologies from our colleagues investigating similar
psychosocial issues with adult heart transplant candidates and recipients
(Dew, 1998;
Rodrigue, Greene, & Boggs,
1994). However, these investigations must include research issues
with specific developmental emphases (e.g., peer relations, school
achievement, cognitive development). Hopefully, in the future, research on
transplantation in children and adolescents will provide greater knowledge
about the concomitant medical, psychological, social, and academic functioning
of heart transplant recipients and their families.
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Acknowledgments |
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We thank Jannette Rey for her continued support throughout this research and her helpful comments during preparation of this manuscript.
Received August 25, 1998; revision received December 29, 1998; revision received April 20, 1999; revision received July 1, 1999; revision received September 1, 1999; accepted September 13, 1999
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