Cognitive function and behavioural status in paediatric heart and heart-lung transplant recipients: the Harefield experience

Introduction

Cardiac transplantation and cardiopulmonary transplantation have become established treatments for end stage cardiac failure in adults,1, 2 but only recently have they been used to treat children with end stage heart or lung disease. Children with chronic illness are more likely to have severe psychological and social difficulties than their healthy peers,3 but very little is known about psychological adjustment after heart or heart-lung transplantation.

Late follow up of children after heart transplantation showed that most had returned to activities appropriate for their age, including school, and that few were having cardiac related symptoms.*RF 4-6* A further study of seven patients suggested that children can “adapt” to the experience of transplantation.7 However, the numbers of patients in these studies were very small. Furthermore, most of them were of school age and were heart rather than heart-lung recipients. Cognitive impairment8, 9 and behavioural and emotional10, 11 disturbance have been reported in children who have had open heart surgery, particularly for cyanotic conditions. Adverse effects have also been reported in parents12 and siblings12, 13 of children with congenital heart disease. Similar problems have been encountered after paediatric renal transplantation14 and bone marrow transplantation.15

The objective of this study was to examine the behaviour and cognitive function of a group of children who had had heart or heart-lung transplantation and to compare them with another group of children who had had non-transplant cardiac surgery and a group of healthy, non- hospitalised children. This cross sectional study was designed to obtain preliminary observations on children after transplantation and to assess the practicality and acceptability of such studies to families and staff.

Results

Forty one children had undergone heart transplantation, of whom 36 had an original diagnosis of cardiomyopathy, four congenital heart disease, and one Kawasaki disease. Twenty four children had received heart-lung transplants, of whom 14 had pulmonary vascular disease and 10 cystic fibrosis. The mean age at assessment was 9.4 years (range 0.6-16.6 years) and the mean time after transplantation at the time of assessment 10 months (range 3-25 months). There were 26 boys and 39 girls, and 50 (77%) came from intact, two parent families. Thirteen (20%) of the patients had had previous cardiothoracic surgery for their disease - primarily those with congenital heart disease - though all of the children had been in hospital at some stage before transplantation. Three heart- lung recipients had received a second transplant for chronic rejection, and a further patient was awaiting retransplantation. At the time of assessment no child was in hospital, though 12 (18%) patients were having problems with repeated infection or rejection episodes, or both.

The 52 children who had other types of cardiac surgery suffered from various congenital cyanotic and acyanotic disorders. Forty nine had had corrective surgery and three palliative surgery. Each patient was seen at a routine outpatient visit 12 months after surgery. A similar proportion of the transplant and cardiac surgery groups had been chronically ill since birth. Though all children in the cardiac surgery group had congenital heart disease, some had been essentially asymptomatic for much of their lives and were, in terms of physical limitations, comparable to many of the children in the transplant group with cardiomyopathy. At the time of assessment seven (13%) children in the cardiac surgery group were having ongoing medical problems.

The transplant and reference groups did not differ with respect to sex and social class distribution but the cardiac surgery group was significantly younger overall than the transplant group. However, when the children were grouped into age bands according to the age criteria of the developmental and cognitive tests16, 17 there were no significant differences in mean ages between the three groups in any age band.

Behaviour at home

On the Rutter A scales for behaviour at home 10 of 41 transplant recipients (24%) had significant problems. In seven cases behaviour was of the neurotic type.20 Behaviour problems were more prevalent in the heart recipients (7/21; 33%) than in the heart-lung recipients (3/20; 15%) but this difference was not statistically significant. There was no significant correlation between the prevalence of behaviour problems and time since transplantation either in the total transplant group (r=-0.005) or in the heart (r=-0.14) and heart-lung (r=-0.17) recipients.

Mean overall IQ and school attainment scores in the three groups. Bars are SD

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TABLE III

Cognitive ability scores on subtests of British ability scales at ages 4.6-17.0 years in the three groups. (Figures in parentheses are SD

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There were no significant differences between the transplant and reference groups in the prevalence of behaviour problems, though the proportion of children with a significant degree of problem behaviour was higher in both the transplant group (10/41; 24%) and cardiac group (5/30; 17%) than in the healthy group (2/31; 6%). Of those children with behaviour problems, a similar proportion in the transplant and cardiac groups had problems of a neurotic nature (seven of 10 and three of five respectively). There were no significant effects of age on the prevalence of behaviour problems in either the transplant or reference groups.

Discussion

Heart and heart-lung transplant operations are major surgical procedures. Transplant recipients require intensive medical support and must adhere to a strict medical follow up programme and drug regimen. Though potentially life saving, transplantation is a high risk procedure and as such is performed only when no other treatment is available. The patients are often chronically ill and many have had prolonged periods in hospital and numerous medical and surgical procedures. Their quality of life and life expectancy before transplantation are extremely poor. Though there is a dramatic improvement in the clinical condition of most patients after transplantation, regular hospital visits are necessary and there is inevitably concern and uncertainty about the future. Both the patient and his or her family must adjust to the fact that the child is no longer chronically sick and in many cases can lead a normal life, sometimes for the first time.

The results of this study are generally encouraging with respect to cognitive performance and behaviour after transplantation. The short term findings in the transplant recipients were similar to those reported for other groups of children who have or have had a chronic illness.14, 15

The number of patients in the younger age group (0-4.5 years) was comparatively small. Nevertheless, the results show that children who had cardiac transplantation before the age of 3 years were developing within the normal range according to the standardised means for the tests, though their develpment was significantly behind that of a group of healthy children. The lower mean subtest scores and overall IQ score obtained by the transplant and open heart surgery patients indicate that cardiac related problems by themselves have implications for early growth and development, which corroborates earlier findings.8, 10, 21, 2

Cognitive development

In the absence of neurological damage, cognitive development in school age children who had had heart or heart-lung transplantation was within the normal range, though their scores were lower than those of a group of non-transplant cardiac surgery patients and a group of healthy children, particularly in short term memory tests. Differences between transplant and cardiac surgery groups may be related to the serious preoperative condition, prolonged hospitalisation, postoperative complications, and need for repeated hospital visits in the transplant group. A similar proportion of transplant recipients and non-transplant cardiac surgery patients were having medical problems at the time of the assessment, so the two groups were comparable in terms of their level of gross medical disability.

Initial diagnosis seemed to be a salient factor, rather than the type of surgical intervention. The open heart surgery group was predominantly children with acyanotic lesions, whereas the transplant group consisted of a higher proportion of children with cyanotic heart disease, for whom cognitive performance might be expected to be impaired.9, 23 There were also children with an initial diagnosis of cardiomyopathy or cystic fibrosis, which are not known to have any deleterious effect on brain development. Hence we must look at cognitive ability in terms of more specific diagnostic categories.

Owing to the retrospective nature of this study no preoperative measures were available to indicate whether IQ was lower before transplantation, but other studies of chronically ill children have found this to be so.15 Transplant recipients had also missed substantially more schooling than the open heart surgery and normal groups, which is likely to influence their performance on academic attainments and contribute to their lower attainment scores. These lower levels of functioning on school attainments may also have been present before transplantation and could be related to problems in concentration that many of these children exhibited, manifested by the poor scores in the short term memory test.

Both the cardiac and normal groups seemed coincidentally to be “bright” samples, with 34.3% (12/35) of cardiac patients and 40.0% (14/35) of normal children obtaining an IQ score higher than one standard deviation above the mean, which was higher than the theoretically expected rate of 15.1%.17 Another study, however, found a high mean IQ score for a sample of the normal population by using the British ability scales (mean IQ 112 (SD 13.4),24 which is consistent with our results.

Behaviour

Our results indicate that there are behaviour problems at home in preschool age children after transplantation, though the numbers of subjects on whom Richman behaviour checklist data were collected were too small for statistical analysis. Aspects of greatest concern to parents included temper tantrums, eating problems, sleeping difficulties, and anxiety, all similar to the problems mentioned by parents of the cardiac surgery and normal children. However, the frequency with which these problems were reported was higher in the transplant and cardiac surgery groups than in the healthy group.

In patients aged 5-17 years the Rutter A data indicated that the proportion with a significant degree of problem behaviour at home was higher than the expected 10% in the general population. In most cases the behaviour was classified as neurotic. From analysis of individual items on the scale, sleeping and eating difficulties, misery, irritability, and anxiety were particularly common. It was clear from interviews with the parents that the problems were related to adaptation after transplantation. For example, parents reported, “He worries about his health a lot and has become a hypochondriac. He answers back now and has a greater fear of needles”; “She seems to have undergone a personality change and now is withdrawn, introverted, and lonely.”

There were differences in the types of behaviour problems manifested by the heart and heart-lung recipients, though these differences were not significant. In general, children with congenital heart disease and cystic fibrosis (the heart-lung group), who in many cases had been chronically ill for much of their lives, tended to cope better with the transplant and hospitalisation. They were used to dealing with illness, medical interventions, and enforced stay in hospital. In contrast, most heart recipients had an initial diagnosis of cardiomyopathy and many of them had had a fairly sudden onset of symptoms before transplantation. Some found it very difficult to accept that they needed a transplant and were extremely anxious, resentful, and aggressive after operation.

Comparison of the transplant and reference groups yielded no significant differences but both groups of hospitalised patients displayed a higher prevalence of problem behaviour than their healthy peers. The prevalence of problem behaviour in the transplant and open heart surgery groups corresponded to that found in other studies of chronically ill children.25, 26 Increased levels of anxiety, depression, and aggression post-operatively have also been found in paediatric kidney and bone marrow transplant recipients.14, 15, 27

The prevalence of problem behaviour at school was lower than that expected in the normal population (10%) and was also low compared with the reference groups. However, this must be interpreted with caution because of the small sample size. Teachers typically commented that the patients had adjusted well to their hospitalisation, and one explanation for the exceptionally low prevalence of problems in the transplant group is that the teachers' own feelings about the enormity of a transplant and their resulting perception of the children affected their responses. Many teachers seemed to regard children with transplants differently from other pupils, making allowances that they would not make for the child's peer group.

Comparability of study groups

It would be preferable if the transplant and reference groups had been individually matched. In practice this is impossible, particularly in matching transplant and cardiac groups. The only significant difference between the three groups in any of the matching criteria was in overall mean ages. Clinically, however, the difference in mean ages of the total groups is of little relevance with respect to psychological outcome and it is of far greater clinical significance to look at the patients within smaller age bands. When the groups were split into more meaningful age bands - according to the basis on which the tests were conducted - these differences were no longer significant. Also, there were no significant correlations between age and any of the outcome measures. A further source of variation within the transplant group concerned the length of time between transplantation and assessment, but there were no significant correlations between time since transplantation and any cognitive or behavioural parameters.

Conclusions

Our data, despite their limitations, provide indications of the behavioural and cognitive status of paediatric patients after heart and heart-lung transplantation. Our study was perceived positively by both families and staff, which was one of the objectives to be assessed. Despite the fact that patients were seen only once for a retrospective assessment, these preliminary observations indicate that there are important psychological effects associated with heart and heart-lung transplantation for children. A similar conclusion was also reached by Uzark and Crowley.28

The preliminary data emphasise the importance of conducting a controlled, prospective study including all family members, in which patients and their families are seen before and at regular intervals after transplantation. More detailed assessment of the child's emotional and behavioural status is necessary, and with larger numbers it will be possible to look more specifically at the influence of family, personality, and medical variables. Such a prospective study is now under way. It will enable us to ascertain whether the transplant group shows changes over time in psychosocial functioning and to look at how the children and their families compare, firstly, with other groups of chronically ill children having stressful and intrusive medical procedures and, secondly, with healthy children. Ultimately our data should allow the development of interventions tailored to the particular needs of this very specialised group of paediatric patients and families.

We thank Dr Tom Sensky (department of psychiatry, West Middlesex University Hospital) and Dr Derek Robinson (school of mathematical and physical sciences, University of Sussex) for helpful comments in the final preparation of the manuscript.