Pediatr Cardiol (2014) 35:536–541 DOI 10.1007/s00246-013-0820-3
Health-Related Quality of Life Experienced by Children With Chromosomal Abnormalities and Congenital Heart Defects Gonzalo Garcia Guerra • Ari R. Joffe • Charlene M. T. Robertson • Joseph Atallah • Gwen Alton • Reg S. Sauve • Irina A. Dinu • David B. Ross • Ivan M. Rebeyka • Western Canadian Complex Pediatric Therapies Follow-up Group
Received: 21 June 2013 / Accepted: 3 October 2013 / Published online: 26 October 2013 Ó Springer Science+Business Media New York 2013
Abstract Long-term outcomes are fundamental in advising parents about the potential future of their children with congenital heart disease (CHD). No published reports have described the health-related quality of life (HRQL) experienced by children with chromosomal abnormalities who had surgery in early infancy for CHD. A study was undertaken to assess HRQL among children with chromosomal abnormalities and CHD. The authors hypothesized that these children have a worse HRQL than healthy children or a cohort of children matched for CHD diagnosis. Infants with chromosomal abnormalities undergoing cardiac surgery for CHD at 6 weeks of age or younger at the Stollery Children’s Hospital between July 2000 and June 2005 were included in
The members of the Western Canadian Complex Pediatric Therapies Follow-up Group are listed in Appendix. G. Garcia Guerra (&) A. R. Joffe C. M. T. Robertson J. Atallah G. Alton I. M. Rebeyka Department of Pediatrics, University of Alberta, 3A3.07 Stollery Children’s Hospital, 8440-112 Street, Edmonton, AB T6G 2B7, Canada e-mail: [email protected]
C. M. T. Robertson G. Alton Pediatric Rehabilitation Outcomes Evaluation and Research Unit, Glenrose Rehabilitation Hospital, Edmonton, AB, Canada R. S. Sauve Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada I. A. Dinu School of Public Health, University of Alberta, Edmonton, AB, Canada D. B. Ross I. M. Rebeyka Department of Surgery, University of Alberta, Edmonton, AB, Canada
the study. The HRQL of these infants was assessed using the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales completed by their parents at a 4-year follow-up evaluation. The study compared the scores for 16 children with normative data. The children with chromosomal abnormalities and CHD had significantly lower mean total PedsQL (71.3 vs. 87.3; p \ 0.0001), Psychosocial Summary (70.3 vs. 86.1; p \ 0.0001), and Physical Summary (74.3 vs. 89.2; p = 0.0006) scores. Compared with the matched children, those with chromosomal abnormalities had a significantly lower median total PedsQL (75.0 vs. 84.6; p = 0.03), Physical Summary (79.5 vs. 96.9; p = 0.007), and School Functioning (68.5 vs. 83.0; p = 0.03) scores. A better understanding of the mechanisms and determinants of HRQL in these children has the potential to yield important implications for clinical practice including clarity for treatment decision making as well as determination of targeted supports and services to meet the needs of these children and their families differentially. Keywords Congenital heart disease Chromosomal abnormalities Pediatric cardiac surgery Healthrelated quality of life
Improved perioperative care for children with complex congenital heart disease (CHD) has led to decreased mortality. Increasing attention currently is being given to longterm outcomes for children after cardiac surgery. Longterm outcomes include neurodevelopment, social performance, and health-related quality of life (HRQL). These long-term outcomes are not only important as markers of a pediatric cardiovascular program performance, but more importantly, they are fundamental in advising parents about the potential future of their children.
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As a multidimensional construct, HRQL includes physical, mental, and social well-being dimensions and not merely the absence of disease. The literature consistently suggests that the clinical condition or severity of disease is not necessarily associated with perceived quality of life . Accordingly, HRQL refers to a person’s subjective and emotional evaluation of his or her health condition and reaction to it . Assessment of HRQL experienced by children with CHD is challenging because of the variability in age, neurodevelopmental capabilities, and diagnoses. No published reports have described the quality of life experienced by children with chromosomal abnormalities who had surgery in early infancy for CHD. To address this issue, a study was undertaken to assess the HRQL of children with chromosomal abnormalities who were treated in infancy for CHD. We hypothesized that children with chromosomal abnormalities who had undergone cardiac surgery for CHD in early life have lower HRQL scores than healthy children or children of the same age with a CHD diagnosis.
Methods This study was part of a prospective interprovincial inception cohort outcomes follow-up project conducted in four provinces of Western Canada. Infants were identified at the time of complex cardiac surgery and followed prospectively. In this study, we included all infants 6 weeks of age or younger with chromosomal abnormalities who were undergoing complex cardiac surgery for CHD, including cardiopulmonary bypass, at the Stollery Children’s Hospital between July 2000 and June 2005. We excluded those patients who received a heart transplant or needed extracorporeal life support. Karyotype and DNA analysis was routinely performed for these patients. Children with chromosomal abnormalities were matched with patients the same age at surgery who had a CHD lesion but no chromosomal abnormalities. Demographic, preoperative, intraoperative, and postoperative variables previously agreed upon were collected prospectively . Long-term follow-up evaluation was discussed with parents or guardians once survival was probable, and after their written consent for participation, contact was made with their respective follow-up clinics at the tertiary site of origin. The follow-up study and database received institutional health research ethics board approval. History and physical measurements were obtained as described previously . The family socioeconomic status was determined using the Blishen Index . Maternal education was indicated by years of schooling. At the age
of 4 years, outcomes assessments were completed at the tertiary site of origin. The HRQL Instrument Assessment of HRQL was performed via the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales (Mapi Research, Lyon, France) completed by the children’s parents at the time of the 4-year-old follow-up visit. This instrument invites parents to report on the quality of life experienced by their child during the past 30 days as seen from the perspective of the child. The PedsQL 4.0 Generic Core Scales is a 23-item tool that encompasses the following domains: Physical Functioning (8 items), Emotional Functioning (5 items), Social Functioning (5 items), and School Functioning (5 items). The items are reverse-scored and linearly transformed to a scale of 0–100. Higher scores indicate better HRQL. A Physical Health Summary score (8 items) is the same as the Physical Functioning subscale. To create a Psychosocial Health Summary score, the mean is computed as the sum of the items divided by the number of items in the emotional, social, and school functioning scales. The PedsQL 4.0 is a well-known instrument used to measure the HRQL of children. Its validity and reliability have been demonstrated and are acceptable for group comparisons [23, 24]. Statistical Analysis Categorical variables are described as frequencies and continuous variables as means ± SDs or as medians and interquartile ranges as appropriate. The PedsQL 4.0 scores for patients with chromosomal abnormalities were compared with published normative values for patients the same age using the t test for independent samples . We also compared the results between patients with chromosomal abnormalities and a cohort of children with the same CHD diagnosis but no chromosomal abnormality using the Mann–Whitney U test. Statistical analysis was performed using STATA (Stata Statistical Software, release 10, 2007; StataCorp LP, College Station, TX, USA), and SAS 9.1 (SAS Institute, Cary, NC, USA) A p value lower than 0.05 was considered statistically significant.
Results During the study period, 21 infants with chromosomal abnormalities underwent complex heart surgery for CHD. Three children were excluded from the study because they received extracorporeal life support, and two patients were lost to follow-up evaluation. Of the remaining 16 children,
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Table 1 Demographics and patient characteristics of children with congenital heart disease With chromosomal abnormality (n = 16) Median (IQR)
Without chromosomal abnormality (n = 16) Median (IQR)
Weight at birth (kg)
Gender: boys: n (%)
Highest inotrope score, preoperative Highest lactate, preoperative (mmol/L)
0 (0–1.5) 1.9 (1.0–2.5)
0 (0–5) 2.8 (1.4–6.9)
Preoperative mechanical ventilation (days)
Lowest PaO2, preoperative (mmHg)
CPB time (min)
DHCA yes: n (%)
Highest inotrope score day 1, postoperative
Highest lactate day 1, postoperative
Postoperative mechanical ventilation (days)
Hospital stay (days)
CPR yes: n (%)
Mother’s years of schooling
PaO2 partial pressure of arterial oxygen; RACHS-1 risk adjustment for congenital heart surgery; CPB cardiopulmonary bypass; DHCA deep hypothermic circulatory arrest; PICU pediatric intensive care unit; CPR cardiopulmonary resuscitation
Table 2 Mean Pediatric Quality of Life Inventory (PedsQL) 4.0 scores for children with chromosomal abnormality and congenital heart disease compared with a normative population Quality scores
Chromosomal (n = 16)
Normative data (n = 907)
Physical Health Summary
Psychosocial Health Summary
Total PedsQL 4.0
SD standard deviation
9 had deletion 22q11.2, 2 had Down syndrome, 1 had Turner syndrome, 2 had deletion 1q21.1, 1 had cri du chat syndrome, and 1 had cat-eye syndrome. The cardiac diagnoses included interrupted aortic arch (n = 9), truncus arteriosus (n = 3), atrioventricular septal defect (n = 2), total anomalous pulmonary venous return (n = 1), and tetralogy of Fallot (n = 1). The children were
assessed at a median age of 54 months [interquartile range (IQR), 50–55 months]. The demographic and perioperative variables did not differ significantly between the children with and without chromosomal abnormalities (Table 1). Compared with normative data, the children with chromosomal abnormalities and CHD had significantly lower mean scores for total PedsQL (71.3 vs. 87.3; p \ 0.0001), Psychosocial Summary (70.3 vs. 86.1; p \ 0.0001), Physical Summary (74.3 vs. 89.2; p = 0.0006), Social Functioning (74.0 vs. 87.7; p = 0.001), School Functioning (61.4 vs. 85.4; p \ 0.0001), and Emotional Functioning (75.0 vs. 84.7; p = 0.006) (Table 2). Compared with matched children who had no chromosomal abnormalities underwent the same cardiac surgery, the children with chromosomal abnormalities had significantly lower median scores for total PedsQL (75.0 vs. 84.6; p = 0.03), Physical Summary (79.5 vs. 96.9; p = 0.007), and School Functioning (68.5 vs. 83.0; p = 0.037). Their Psychosocial Summary (72.0 vs. 79.0; p = 0.205) and Emotional Functioning (75.0 vs. 85.0; p = 0.447) scores were lower, but this difference was not statistically significant. The Social Functioning scores (77.5 vs. 75.0; p = 0.57) were similar in the two groups (Table 3). The HRQL scores did not differ significantly between the children with deletion 22q11.2 and those with other chromosomal abnormalities (data not shown).
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Table 3 Median Pediatric Quality of Life Inventory (PedsQL) 4.0 scores for children with congenital heart disease with and without chromosomal abnormality Quality scores
With chromosomal abnormality (n = 16)
Without chromosomal abnormality (n = 16)
Social Functioning School Functioning
Physical Health Summary
Psychosocial Health Summary
Total PedsQL 4.0
IQR interquartile range
Discussion In this prospective cohort study of 16 children with chromosomal abnormalities who underwent complex heart surgery for CHD during early infancy, HRQL was evaluated at the age of 4 years using the PedsQL 4.0. The children with chromosomal abnormalities and CHD had significantly lower total PedsQL 4.0 scores than the normative population, reflecting overall worse HRQL. These children also had significantly lower scores in all the HRQL dimensions (i.e., Emotional Functioning, School Functioning, Social Functioning, Physical Summary, and Psychosocial Health Summary) compared with population norms. Compared with the children who had similar CHD but no chromosomal abnormalities, the patients with chromosomal abnormalities also showed significantly lower total HRQL, Physical Summary, and School Functioning scores. However, those with chromosomal abnormalities had Psychosocial Summary, Emotional Functioning, and Social Functioning scores similar to those of other children with CHD who had surgery in early infancy. The increased survival after surgical repair of CHD has meant that outcome studies investigating this group of patients have evolved to include more comprehensive longterm outcomes such as neurodevelopment function and HRQL [1, 4, 12]. Having a greater understanding of the multidimensional impact that these surgical procedures have on the long-term experience of these children with CHD and their families is important to the optimization of health care interventions and improvement of long-term outcomes. However, the few HRQL studies that have investigated children with CHD usually excluded patients with chromosomal abnormalities . Children with chromosomal abnormalities, especially those with deletion 22q11.2, are known to have a higher incidence of developmental delay as well as behavioral and
psychiatric disorders [2, 8]. Looman et al.  reported that children with deletion 22q11.2 have a lower HRQL than a normative population or children with chronic disease. However, their study included children with and without CHD. Developmental delay, behavioral problems, and lower HRQL also are common among children with trisomy 21 . Consequently, they have been systematically excluded from most studies on HRQL and CHD [3, 5–7, 9–11, 14, 15, 17, 18, 21]. This may be premature because findings have shown that physical conditions and severity of disease are not always well correlated with the quality of life level . Previous HRQL studies investigating children with CHD have been performed with different patient populations, have included different reference populations, have used different HRQL instruments, and have shown conflicting results . Our results for children with chromosomal abnormalities are similar to those of previous studies in which children with CHD had worse HRQL than healthy control subjects [3, 5, 7, 10, 17, 19, 21]. Moyen Laane et al.  conducted a study on HRQL and CHD in which a subgroup analysis of 29 children with CHD and ‘‘associated syndromes/congenital defects’’ showed lower scores for self-esteem and peer acceptance (meaning low self-esteem and low peer acceptance) and higher scores for satisfaction with social support and psychosomatic problems than healthy control subjects. Children with CHD and chromosomal abnormalities may generate social support for the family, or these families may develop coping mechanisms that protect these children in their social sphere, at least while they are young. In a population-based study, children with trisomy 21 showed lower HRQL scores than a normative population, but the study did not include a separate analysis comparing these children and children with CHD . These studies, despite similar results, differed from ours in several
respects. Some of studies included surgical and nonsurgical patients. Others included only surgical patients, but the ages at surgical repair or assessment were variable [3, 10, 17, 19, 21]. Our previous study of 130 children with CHD who underwent surgical repair early in infancy but had no chromosomal abnormalities also showed a lower HRQL than a normative population of the same age . In the current study, the children with chromosomal abnormalities had a significantly lower HRQL than the children with the same CHD but no chromosomal abnormalities, especially in the Physical Functioning and School Functioning domains. However, the Psychosocial Summary and Social Functioning scores were not significantly lower. The lack of statistical significance could have been due to the lack of statistical power or could indicate that there really was no difference. In favor of the latter is the fact that the Emotional Functioning scores were very similar between the children with and without chromosomal abnormalities. This is an interesting and positive finding that might represent good adaptation of these children to their environment. Nevertheless, these patients were 4 years old and may not yet have faced some of the challenges that will come in their future school-age lives. At the age 4 years, most of their social activities and their emotions are still closely related to their parents . Our study has the strength of being an inception cohort of patients who all had their cardiac surgery very early in infancy, were assessed at the same age (age of 4 years), and were compared with a normative population of the same age and with a matched cohort of patients who had the same CHD but no chromosomal abnormality. To our knowledge, this is the first study specifically to report HRQL outcomes for children with chromosomal abnormalities and CHD.
Study Limitations The HRQL was evaluated using the parents’ perspective. Several studies have shown significant variability between parents and children in their reports of HRQL [16, 21]. At the time of the follow-up evaluation, most of these children were 4 years old, an age at which only proxy reports can be obtained. Reassessment of the same cohort in the future will allow comparison between children and parents. Two patients were lost to follow-up evaluation. Although this is a small number, it represents 12 % of our patients with chromosomal abnormalities, which could have caused selection bias. We did not have the socioeconomic status (SES) of the normative population used by Varni et al. to compare with our cohort. Nevertheless, the SES of our cohort did not
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differ significantly from that reported for the Canadian population [4, 24]. Most of our cohort had deletion 22q11.2. Whether our results can be extrapolated to children with other chromosomal abnormalities is unknown. Our cohort showed no significant differences in HRQL scores between the children with deletion 22q11.2 and those with other chromosomal abnormalities. Although a comparison of children who have deletion 22q11.2 between those with and without CHD seems ideal, we have not found any reports of HRQL for children with deletion 22q11.2 diagnosed in early infancy who had no CHD. One study of 45 children with deletion 22q11.2 showed no difference in HRQL between the children with and without CHD . This supports our finding that children with deletion 22q11.2 have lower HRQL scores than children with CHD but no chromosomal abnormalities. The chromosomal abnormality seems be responsible for much of the lower scores. Also, our results come from a small cohort of patients and should be interpreted with caution. Finally, the number of children did not allow investigation of potentially modifiable risk factors for lower HRQL.
Conclusions The findings of this study invite further research with the population investigated. A better understanding of mechanisms and determinants of HRQL experienced by these children has the potential to yield important implications for clinical practice including clarity for treatment decision making as well as determination of targeted supports and services to differentially meet the needs of these children and their families. At 4 years of age, the children in our cohort with chromosomal abnormalities and CHD had significantly lower HRQL than a normative population or a matched cohort with CHD but no chromosomal abnormalities. By describing how the survivors may perform in society and experience daily living, HRQL outcomes contribute to a better understanding of the outcome experienced by these patients and their families. Further research examining key elements that determine the long-term outcomes for these children and their change over time while the children are developing is needed. Strategies for the care of children with CHD should take into account not only the medical aspects of the disease and its treatment but also factors affecting the external, interpersonal, and personal spheres of these children’s lives. Acknowledgments Financial support for this study was provided by the Registry and Follow-up of Complex Pediatric Therapies Project, Alberta Health and Wellness.
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Appendix D Moddemann, Winnipeg, MB; P Blakley, Saskatoon, SK; J Bodani, Regina, SK.
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