OUTLINE
In October 2000, Left Heart Matters agreed to fund a ClinPsyD research project into the intellectual and neurological functioning of children with hypoplastic left heart syndrome (HLHS). The aim of this study was to examine the intelligence and adaptive behaviour of a cohort of classic HLHS children who had completed all three stages of the Norwood procedure between 01/06/91 and 31/12/98, at the Birmingham Children's Hospital (BCH).

Using Wechsler age appropriate intelligence tests, 36 children were assessed between 25 February and 25 November 2000. These included 11 HLHS children, 9 siblings and thirteen children with a range of other congenital heart disorders.

Data relating to possible predictors of neurological and intellectual outcome were retrieved from medical notes and a comprehensive neurological examination performed. Parents completed the Child Behaviour Checklist (CBCL) and two self-report measures of anxiety and depression.

Summary of Findings
Statistically significant differences were found in intellectual functioning between the HLHS group and sibling controls in verbal IQ (p=.017) and full-scale IQ (p=.011). Mean VIQ scores were 86.27 for the nine HLHS children with siblings, 98.11 for the siblings and 93.69 for the children with other heart disorders. FSIQ scores were 88.27, 98.56 and 87.23 respectively. There were no statistically significant differences in IQ scores between the children with HLHS and other cardiac lesions.

Other specific cognitive deficits, such as memory, attention and executive problems are not reflected in a single IQ score. Additional difficulties such as these may lead to learning difficulties later on and should be taken into account when considering the longer-term outcomes of HLHS children.

One HLHS child had a neurological score that was lower than expected suggesting a mild functional impairment, and one sibling had lateral nystagmus. Factors most predictive of intellectual outcome are seizures, length of stay in intensive care and duration of cardiopulmonary bypass. However, due to the small sample size the analysis of predictors can only be exploratory and the results should be treated with caution.

The CBCL results demonstrated differences in the conduct of children with heart conditions compared to a sibling control group. This may be because of cognitive problems that were not assessed in the present study.

Mothers of HRHS children were more anxious than mothers of HLHS children and fathers of the HRHS children had a higher mean depression score than fathers of the group of HLHS children.

The Assessments and Measures
To assess intellectual functioning, children under the age of 6 completed the Wechsler Pre-school and Primary Scale of Intelligence-Revised (WPPSI-R). Older children completed the Wechsler Intelligence Scale for Children (WISC-III). The WISC III and WPPSI-R are well-constructed and standardised tests for the assessment of intellectual ability in children and adolescents.

Both scales contain a variety of verbal and performance subtests. The verbal subtests measure planning ability, non-verbal reasoning, abstract thinking, short and long-term memory, visual perception, social judgement, social adaptability, speed of mental processing, learning ability and problem solving ability. The performance dimension reflects non-verbal reasoning, visual-spatial and visuo-motor skills.

Neurological development was assessed using a functional assessment instrument especially designed for use with children. This instrument is used as a measure of severity of disability and the need for assistance to perform activities of daily living. The rating procedure involved direct observation and an interview with the parents to obtain detailed information regarding their children's abilities. Among other things, these measures included self-care, bladder and bowel control, communication and comprehension, social interaction and physical abilities. Parents also completed a Child Behaviour Checklist, which provided information regarding the children's social functioning and development.

Since caring for a child with a serious illness can be extremely difficult, information was also obtained from parents about their own levels of stress and anxiety. Additional detailed medical information regarding clinical and operational data, was obtained from children's medical records.

This study was approved by the Birmingham Children's Hospital Ethics Committee and signed consent obtained from parents and children

The Outcomes

• It is possible to assess the intellectual, behavioural and neurological functioning in HLHS children following the Fontan procedure.
• Results of these tests can be compared with relevant surgical information to allow predictions to be made regarding intellectual functioning post-surgery.
• None of the HLHS children demonstrated significant neurological abnormalities or severe functional impairment. Three HLHS children showed mild functional impairment.
• Among the children with other congenital heart malformations, two performed poorly on measures of neurological functioning and three had microcephaly.
• A number of outcomes appeared to be associated with a reduction in intellectual functioning such as the presence of clinical seizures, length of stay in ITU and, to a lesser extent, duration of cardiopulmonary bypass. Although seizures frequently occur after open-heart surgery (Miller 1994) there were only 2 recorded in this study population.
• Compared to children with other congenital heart conditions, HLHS children do not necessarily have a poor outcome in terms of intellectual functioning.
• Based on a relatively small sample size, the generalisability of these findings is limited.

Background
Despite the improvement in treatment for children with HLHS, little is known regarding their intellectual and neurological functioning. Because of their satisfactory psychomotor development, there has been little stimulus to examine the question of the effects of numerous surgical procedures on their neurological and intellectual functioning to date.

Studies show that the effects of chronic cyanosis, multiple cardiac operations, and the known incidence of congenital and acquired brain problems associated with HLHS, increase the possibilities for intellectual deficit. Reports have demonstrated that children who have been operated on for other congenital heart conditions have a below normal IQ, particularly in the presence of chronic cyanosis, or cardiac arrest. There is also evidence that heart surgery performed with circulatory arrest is associated with a higher risk of delayed motor development and neurologic problems than is surgery with low-flow bypass. Past studies have found that some children have persisting long-term neurological problems directly related to the perioperative period., and/or major developmental disabilities.

A recently study that compared the neurodevelopment of two groups of children with congenital heart disease, found that whilst HLHS children had significantly lower scores than the non-HLHS group, neither subgroup scored significantly different to the standard population on measures of IQ. However, they did find that circulatory arrest and perioperative seizures were predictive of neurodevelopmental outcome.

In the present study, a total of eleven HLHS children were assessed and compared with thirteen other children with a range of other congenital heart disorders. Nine of the HLHS children had siblings, which allowed for a direct comparison of their IQ scores and neurological functioning. The use of sibling control participants allowed for the exclusion of socio-economic differences otherwise inherent in any comparison with the normal population. Whilst no control group can be considered truly ideal, the groups in this study may be as close as we can get to that ideal.

The British Psychological Society's guidelines on the criteria that should be used to determine Learning Disability, states that a person has a learning disability if there is a significant impairment of intellectual functioning, a significant impairment in social/adaptive functioning, age of onset before adulthood and an IQ score at or below 70. Whilst none of the children assessed in this study met these criteria, some had specific learning difficulties necessitating additional educational support and statementing.

For families considering surgical intervention, knowledge of the intellectual and neurodevelopmental outlook for patients with HLHS is an important aspect in the early decision making process. It is hoped that data on intellectual development will provide families with more information to guide their expectations of children with HLHS.

FURTHER DETAILS OF RESEARCH
The Participants
In this study the diagnosis of HLHS consisted specifically of an underdeveloped (hypoplastic) left ventricle, mitral valve and aortic arch; normally related great vessels; and a right ventricular dependent circulation. Hypoplastic left hearts with additional complex features (e.g., transposition of the great arteries, double outlet right ventricle and/or atrioventricular septal defect) were excluded. Siblings chosen were those closest in age to the child with HLHS.

Between 1996 and 2000 twenty-three children were operated on at BCH for HLHS. Of these, twenty-one children survived the Fontan procedure and contact information obtained for all of them. Individual letters inviting families to participate, together with information about the study, were sent to the families of HLHS children by Left Heart Matters. This was followed up a few weeks later with a phone call, which provided the opportunity of making direct contact with families.

Two children were later excluded from the study because they live abroad and two families could not be contacted. Nineteen families were subsequently approached to participate in the study. Of these, three declined participation mainly because they were reluctant to allow their children to undergo further testing which they did not consider relevant to the child's general health. These reasons were respected with no further contact made. Assessment appointments were offered to two families who failed to attend.

In total fourteen families participated in the study. Of these, three children were later excluded from the analysis because they did not meet the full inclusion criteria. The average ages of children at the time of assessment were 5.6 years for the HLHS children, 7.2 years for the HRHS children and 6.7 years for the siblings.

Conclusion
The mean full-scale IQ for HLHS children in this study is no worse than that of HRHS children and is similar to that reported by other investigators, although the sample size was small and the study may not have been sensitive to smaller differences in IQ. Statistically significant differences were found between the verbal and full-scale IQs of HLHS children post Fontan and their corresponding siblings.

Furthermore, IQ scores do not take into account other specific cognitive deficits, such as memory, attention and executive difficulties. Additional problems, such as these may lead to learning difficulties later on. All of these factors should be taken into account when considering longer-term outcomes of HLHS children.

Remaining Questions
There are many factors that impact upon intellectual and developmental outcome in children undergoing open-heart surgery for HLHS. Reports indicate that abnormal brain MRI is common after cardiopulmonary bypass with deep hypothermia, which may be associated with abnormal neurologic examination and a reduction in IQ.

However IQ scores do not provide diagnostic information regarding specific cognitive deficits, such as memory, attention and executive difficulties, which may lead to learning difficulties later on. Future research should therefore include a detailed neuropsychological assessment of factors such as memory, attention, executive functioning and language skills.

Since the present study did not assess the range of cognitive deficits that can give rise to behavioural problems, it is possible that difficulties with memory, attention and executive skills could be contributing to the increase in behavioural problems found in children with heart conditions. This remains an area for future research.

One should also consider the fact that a child's intellectual development is greatly dependent upon psychological and psychosocial influences. As well as information regarding neuropsychological functioning, it is equally as important to gain insight into other difficulties faced by HLHS children. Future research should assess the daily fears and challenges HLHS children are faced with, such as altered physical appearance, demanding treatment regimes, school absences and lack of stamina, which may impact on their quality of life.

In order to provide families with comprehensive information regarding outcome following surgical intervention for congenital heart disease, it is recommended that a detailed analysis of the whole problem, not only from a clinical and surgical perspective, but also from the psychological and cognitive aspects, should be conducted.

Whilst parents can be more optimistic about their child's intellectual functioning (in that it may not be any worse than children with HRHS), a long-term prospective analysis is required to address the questions raised by the study.

Further Information
Summary information was presented at the Birmingham Pediatric Cardiac Workshop and at the 3rd World Pediatric Cardiology Congress in Toronto in May 2001. Further information will be presented at the Hypoplastic Left Heart Syndrome Symposium in Liverpool in September 2001. A detailed report of these findings will be submitted to the Archives of Disease in Childhood for peer review.

Further enquiries about this study can be made by contacting Dr. Jacqueline Blyth email: Jacqueline.Blyth@bhamchildrens.wmids.nhs.uk