Original Article
Surgical outcome of congenital heart disease in Down’s syndrome
Asian Cardiovascular & Thoracic Annals 21(2) 166–169 ß The Author(s) 2012 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0218492312450701 aan.sagepub.com
Praveen S Lal, Bhushan Chavan, Vimala Rani Devendran, Roy Varghese, Uday Charan Murmu and Raghavannair Suresh Kumar
Abstract Background and objective: only a few studies have compared surgical outcomes in children with and without Down’s syndrome. The purpose of this study was to investigate the surgical outcome in children with Down’s syndrome and congenital heart disease and to compare it with that in age- and sex-matched non-Down controls. Patients and methods: the charts of 32 consecutive Down’s syndrome patients who underwent surgery for congenital heart disease in a single center from January 2006 to May 2010, were compared with the data of 32 age- and sex-matched non-Down controls, focusing on comparative echocardiographic details, surgical outcome, and intensive care unit data. The data were compared using the 2-group t test. The children were followed up for a median period of 48 months. Results: the most common cardiac lesion in the study group was ventricular septal defect (41%) followed by atrioventricular septal defect (28%). Ventilation and intensive care unit stay were significantly longer in Down’s syndrome children, with a trend towards more respiratory complications. At a median follow-up of 48 months, there were no cardiac events or mortality in the study group. Simple lesions were more common than atrioventricular septal defect in Down’s syndrome. Conclusion: children with Down’s syndrome can be operated on with negligible mortality and good functional outcome, but with a higher surgical morbidity.
Keywords Complete atrioventricular septal defect, down syndrome, heart defects, congenital, postoperative complications, treatment outcome
Introduction Down’s syndrome (DS) is the most common genetic cause of developmental disability and mental retardation in children. It occurs in 1:700 live births. Whereas the incidence of congenital heart disease (CHD) in the general population is 0.8%, it is as high as 40%–50% in children with DS. Although atrioventricular septal defect (AVSD) is the best-known CHD associated with DS (43%), the range and frequency of CHD in DS children seem to differ in different parts of the world. Previous studies have shown conflicting outcomes after CHD surgery for patients with DS; some reports showed good outcomes, and others found high morbidity and mortality. There are very few studies that have made a head-to-head comparison of DS children with non-DS children with regard to surgical outcomes in CHD. The previous studies focused primarily
on patients undergoing AVSD repair. The purpose of this study was to investigate the surgical outcome of CHD in DS and compare it with that in age- and sex-matched non-DS children with similar CHD.
Patients and methods This was a retrospective chart review of 32 DS patients who underwent surgery for CHD in a single center Departments of Paediatric Cardiology and Cardiac Surgery, Institute of Cardiovascular Diseases, The Madras Medical Mission, Chennai, India Corresponding author: Raghavannair Suresh Kumar, DM, Department of Paediatric Cardiology, Institute of Cardiovascular Diseases, Madras Medical Mission, 4A Dr J.J. Nagar, Mogappair, Chennai–600037, India. Email: [email protected]
Lal et al.
167 Table 1. Intensive care unit data of children with and without Down’s syndrome undergoing cardiac surgery. Group
Ventilation (h)
ICU stay (days)
Additional support* (n)
Study Controls p value
63.2 100.45 28.3 22.58 Not significanty
6.9 5.68 4.0 3.60 Not significanty
15 14 Not significantz
*The standard inotropic support protocol during the study period was dopamine 5 mg kg1 min1. Any additional inotropics (adrenaline, noradrenaline, milrinone) were administered when there was an indication (hypotension or bradycardia). yPaired t test. zFischer’s exact test. ICU: intensive care unit.
from January 2006 to May 2010. The records of 32 ageand sex-matched non-DS children operated during the same period were analyzed as a control group. The study was approved by the institutional ethics committee. DS was confirmed in all cases by karyotyping. A detailed chart review was made focusing on twodimensional echocardiographic diagnosis, surgical outcome, intensive care unit (ICU) data (duration of ventilation, ICU stay, inotropic support), and complications. The diagnostic categories were identical. The children were followed up for a period ranging from 22 to 72 months (median, 48 months). Data are given as mean standard deviation or median and range. The ICU parameters in the 2 groups were compared using the two-group t test. Categorical data were analyzed using Fisher’s exact test. A p value < 0.05 was considered significant.
Results There were 21 girls and 11 boys in the study group, with a mean age of 38.3 7.6 months and a mean weight of 10.6 6.4 kg. The control group had an identical sex distribution, a mean age of 37.3 6.8 months, and a mean weight of 11.8 7.6 kg. The most common CHD in the DS group was ventricular septal defect (41%) followed by AVSD (28%), tetralogy of Fallot (15%), patent ductus arteriosus (13%), and ostium secundum atrial septal defect (3%). The ICU data are shown in Table 1. There was no significant difference between the 2 groups with regards to complications (Table 2), although the DS group had a tendency to have more numbers in each category. The data were separately analyzed for AVSD (Table 3); the mean duration of ICU stay was significantly longer for DS children in this subgroup (p = 0.01). At a median follow up of 48 months (range, 22–72 months), there were no cardiac events or mortality in the DS group, but there was one death in a non-DS child, due to septicemia. The non-DS group had more residual mitral regurgitation (6 vs. 2), but the numbers were too small for statistical analysis.
Table 2. Major complications in the intensive care unit. Complication
Study group
Controls
p value*
Respiratory Arrhythmias PH crisis Mortality
10 4 0 0
5 2 2 1
Not Not Not Not
significant significant significant significant
*Fischer’s exact test. PH: pulmonary hypertensive.
Discussion The last few decades have shown a significant change in the approach to CHD surgery in children with DS. As the life expectancy and treatment for non-cardiovascular morbidity in DS patients has improved, it has became necessary and ethical to take care of their CHD effectively. Because the outcome of CHD surgery in general has been steadily improving due to refinements in surgical technique and perioperative care, it is possible to take up the challenge of cardiac surgery in DS children. The prevalence of DS in the US has increased by 31% (from 9 to 12 per 10,000 live births) in the last 3 decades.1 This means that the number of children with DS seeking cardiac care has risen in the recent past, and will continue to rise. With the current standard of pediatric cardiac care, it is important to see whether DS children have a different surgical outcome to non-DS patients in terms of ICU requirements, to predicted resource consumption in health care. Complete AVSD is the characteristic cardiac lesion in DS.2,3 However the prevalence of this lesion in DS seems to vary in different geographical regions of the world. In epidemiological studies in the United States and Europe, complete AVSD was found in 60% of patients.4,5 In Asia, isolated ventricular septal defect has been reported to be the most common defect, observed in approximately 40% of patients.6 In Latin America, secundum atrial septal defect was reported to be the most common lesion.7 In our series, AVSD contributed to only 28% of DS children undergoing surgery, with simpler lesions such as atrial septal defect,
168
Asian Cardiovascular & Thoracic Annals 21(2) Table 3. Surgical outcome of complete atrioventricular septal defect repair. Variable
Study group
Controls
p value*
Mortality Duration of ventilation (h) ICU stay (days) Additional inotropic support Complications Respiratory Arrhythmia Late redo surgery
0 68.2 46 7.9 4.0 7
0 37.4 29 5.7 5.5 5
0.0025 Not significant Not significant
4 2 0
1 1 1
Not significant Not significant Not significant
*Fischer’s exact test. ICU: intensive care unit.
ventricular septal defect, and patent ductus arteriosus together accounting for 50%. Fudge and colleagues8 recently reported the surgical outcome of DS patients, based on a US national database, compared to that of non-DS children; in this large series (n = 4350), there was no difference in mortality between the 2 groups, even though patients with DS were younger at surgery (median age 5.2 months). Duration of hospital stay was longer for atrial and ventricular septal defect closure and intracardiac repair of tetralogy of Fallot in DS children. In our series, we also observed no difference in mortality between the 2 groups. Median age at surgery was 10 months, and DS children had a significantly longer period of ventilation and ICU stay compared to non-DS children. These findings could be attributed to a larger proportion of patients with DS having preoperative risk factors and postoperative complications. Malec and colleagues9 also reported prolonged ventilation and longer duration of ICU stay in patients with DS. Respiratory complications and infections are known to play a significant role in morbidity and mortality in DS.10 Chronic upper airway obstruction, increased secretions and gastroesophageal reflux leading to chronic aspiration may be some of the contributing factors. Abnormalities in T lymphocyte maturation and function in DS patients predispose them to frequent infections.11 Fudge and colleagues8 also reported a higher incidence of respiratory and infectious complications in their study. Our study observed a trend towards a higher incidence of respiratory and infectious complications in DS, but it was not statistically significant. Several reports have noted lower mortality for AVSD in DS compared to non-DS children.8,12,13 It has been postulated that more favorable cardiac anatomic features, such as better atrioventricular valve morphology and fewer left-sided obstructive lesions, may be responsible for better outcomes in DS children
with AVSD. In the subgroup analysis of complete AVSD in our study, there was a significant difference in the mean duration of ventilation, while all other parameters were similar to those of non-AVSD surgery. Residual and progressive mitral regurgitation is a matter of major concern following AVSD surgery. Residual mitral regurgitation and redo surgery are more common after a non-DS AVSD repair.12 The observation in our study, where 6 patients in this category had 52þ mitral regurgitation (one requiring redo surgery), compared to only 2 with significant regurgitation in the DS group, supports this theory, but the numbers were too small for statistical analysis. Our series did not contain any patient undergoing Fontan track surgery. In view of the reported high mortality and morbidity of univentricular surgery in DS,8 the approach that we have followed is to avoid Fontan surgery in DS children in our resource-scarce scenario. Tucker and colleagues1 reported a higher incidence of postoperative complete heart block in DS children undergoing ventricular septal defect closure. A similar finding was also noted by Fudge and colleagues.8 In our series, there was no complete heart block in DS children; indeed, the only pacemaker implantation was performed in a non-DS patient for postoperative complete heart block following ventricular septal defect closure. This was a retrospective case-control study. The study design may have inherent statistical limitations that could affect conclusions with regard to significance. However, we concluded that simpler lesions outnumbered complete AVSD in this series, and DS children could be operated on with negligible mortality. There was a significantly longer duration of ventilation and ICU stay in such children, compared to non-DS patients, and a trend towards a higher incidence of respiratory complications. The intermediate-term functional status of DS children was comparable to that of non-DS children, with isolated instances of reintervention.
Lal et al. Acknowledgment The authors gratefully acknowledge the contribution of Dr Nagarajan Gurumani, MSc, PhD, in the statistical analysis of the study.
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Conflicts of interest statement None declared.
References 1. Shin M, Besser LM, Kucik JE, Lu C, Siffel C, Correa A, et al. Prevalence of Down syndrome among children and adolescents in 10 regions of the United States. Pediatrics 2009; 124: 1565–1571. 2. Tubman TR, Shields MD, Craig BG, Mulholland HC and Nevin NC. Congenital heart disease in Down’s syndrome: two-year prospective early screening study. BMJ 1991; 302: 1425–1427. 3. Laursen HB. Congenital heart disease in Down’s syndrome. Br Heart J 1976; 38: 32–38. 4. Mathew P, Moodie D, Sterba R, Murphy D, Rosenkranz E and Homa A. Long-term follow-up of children with Down syndrome with cardiac lesions. Clin Pediatr (Phila) 1990; 29: 569–574. 5. Figueroa JD, Magana BD, Hach J, Jimenez C and Urbina R. Heart malformations in children with Down syndrome. Rev Esp Cardiol 2003; 56: 894–895. 6. Jacobs EG, Leung MP and Karlberg J. Distribution of symptomatic congenital heart disease in Hong Kong. Pediatr Cardiol 2000; 21: 148–157.
169 7. Vida VL, Barnoya J, Larrazabal LA, Gaitan G, de Maria Garcia F and Castan˜eda AR. Congenital cardiac disease in children with Down’s syndrome in Guatemala. Cardiol Young 2005; 15: 286–290. 8. Fudge JC, Li S, Jagger J, O’Brain SM, Peterson ED, Jacob JP, et al. Congenital heart surgery outcomes in Down syndrome. Analysis of a national clinical database. Pediatrics 2010; 126: 315–322. 9. Malec E, Mroczek T, Pajak J, Januszewska K and Zdebska E. Results of surgical treatment of congenital heart defects in children with Down’s syndrome. Pediatr Cardiol 1999; 20: 351–354. 10. Yang Q, Rasmussen SA and Friedman JM. Mortality associated with Down’s syndrome in the USA from 1983 to 1997: a population-based study. Lancet 2002; 359: 1019–1025. 11. Kusters MA, Verstegen RH, Gemen EF and de Vries E. Intrinsic defect of the immune system in children with Down syndrome: a review. Clin Exp Immunol 2009; 156: 189–193. 12. Formigari R, Di Donato RM, Gargiulo G, Di Carlo D, Feltri C, Picchio FM, et al. Better surgical prognosis for patients with complete atrioventricular septal defect and Down’s syndrome. Ann Thorac Surg 2004; 78: 666–672. 13. Nisli K. Prevalence of congenital heart defect in patients with Down’s syndrome. J Pediatr (Rio J) 2009; 85: 377–378. 14. Tucker EM, Pyles LA, Bass JL and Moller JH. Permanent pacemaker for atrioventricular conduction block after operative repair of perimembranous ventricular septal defect. J Am Coll Cardiol 2007; 50: 1196–1200.
Surgical outcome of congenital heart disease in Down’s syndrome
Asian Cardiovascular & Thoracic Annals 21(2) 166–169 ß The Author(s) 2012 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0218492312450701 aan.sagepub.com
Praveen S Lal, Bhushan Chavan, Vimala Rani Devendran, Roy Varghese, Uday Charan Murmu and Raghavannair Suresh Kumar
Abstract Background and objective: only a few studies have compared surgical outcomes in children with and without Down’s syndrome. The purpose of this study was to investigate the surgical outcome in children with Down’s syndrome and congenital heart disease and to compare it with that in age- and sex-matched non-Down controls. Patients and methods: the charts of 32 consecutive Down’s syndrome patients who underwent surgery for congenital heart disease in a single center from January 2006 to May 2010, were compared with the data of 32 age- and sex-matched non-Down controls, focusing on comparative echocardiographic details, surgical outcome, and intensive care unit data. The data were compared using the 2-group t test. The children were followed up for a median period of 48 months. Results: the most common cardiac lesion in the study group was ventricular septal defect (41%) followed by atrioventricular septal defect (28%). Ventilation and intensive care unit stay were significantly longer in Down’s syndrome children, with a trend towards more respiratory complications. At a median follow-up of 48 months, there were no cardiac events or mortality in the study group. Simple lesions were more common than atrioventricular septal defect in Down’s syndrome. Conclusion: children with Down’s syndrome can be operated on with negligible mortality and good functional outcome, but with a higher surgical morbidity.
Keywords Complete atrioventricular septal defect, down syndrome, heart defects, congenital, postoperative complications, treatment outcome
Introduction Down’s syndrome (DS) is the most common genetic cause of developmental disability and mental retardation in children. It occurs in 1:700 live births. Whereas the incidence of congenital heart disease (CHD) in the general population is 0.8%, it is as high as 40%–50% in children with DS. Although atrioventricular septal defect (AVSD) is the best-known CHD associated with DS (43%), the range and frequency of CHD in DS children seem to differ in different parts of the world. Previous studies have shown conflicting outcomes after CHD surgery for patients with DS; some reports showed good outcomes, and others found high morbidity and mortality. There are very few studies that have made a head-to-head comparison of DS children with non-DS children with regard to surgical outcomes in CHD. The previous studies focused primarily
on patients undergoing AVSD repair. The purpose of this study was to investigate the surgical outcome of CHD in DS and compare it with that in age- and sex-matched non-DS children with similar CHD.
Patients and methods This was a retrospective chart review of 32 DS patients who underwent surgery for CHD in a single center Departments of Paediatric Cardiology and Cardiac Surgery, Institute of Cardiovascular Diseases, The Madras Medical Mission, Chennai, India Corresponding author: Raghavannair Suresh Kumar, DM, Department of Paediatric Cardiology, Institute of Cardiovascular Diseases, Madras Medical Mission, 4A Dr J.J. Nagar, Mogappair, Chennai–600037, India. Email: [email protected]
Lal et al.
167 Table 1. Intensive care unit data of children with and without Down’s syndrome undergoing cardiac surgery. Group
Ventilation (h)
ICU stay (days)
Additional support* (n)
Study Controls p value
63.2 100.45 28.3 22.58 Not significanty
6.9 5.68 4.0 3.60 Not significanty
15 14 Not significantz
*The standard inotropic support protocol during the study period was dopamine 5 mg kg1 min1. Any additional inotropics (adrenaline, noradrenaline, milrinone) were administered when there was an indication (hypotension or bradycardia). yPaired t test. zFischer’s exact test. ICU: intensive care unit.
from January 2006 to May 2010. The records of 32 ageand sex-matched non-DS children operated during the same period were analyzed as a control group. The study was approved by the institutional ethics committee. DS was confirmed in all cases by karyotyping. A detailed chart review was made focusing on twodimensional echocardiographic diagnosis, surgical outcome, intensive care unit (ICU) data (duration of ventilation, ICU stay, inotropic support), and complications. The diagnostic categories were identical. The children were followed up for a period ranging from 22 to 72 months (median, 48 months). Data are given as mean standard deviation or median and range. The ICU parameters in the 2 groups were compared using the two-group t test. Categorical data were analyzed using Fisher’s exact test. A p value < 0.05 was considered significant.
Results There were 21 girls and 11 boys in the study group, with a mean age of 38.3 7.6 months and a mean weight of 10.6 6.4 kg. The control group had an identical sex distribution, a mean age of 37.3 6.8 months, and a mean weight of 11.8 7.6 kg. The most common CHD in the DS group was ventricular septal defect (41%) followed by AVSD (28%), tetralogy of Fallot (15%), patent ductus arteriosus (13%), and ostium secundum atrial septal defect (3%). The ICU data are shown in Table 1. There was no significant difference between the 2 groups with regards to complications (Table 2), although the DS group had a tendency to have more numbers in each category. The data were separately analyzed for AVSD (Table 3); the mean duration of ICU stay was significantly longer for DS children in this subgroup (p = 0.01). At a median follow up of 48 months (range, 22–72 months), there were no cardiac events or mortality in the DS group, but there was one death in a non-DS child, due to septicemia. The non-DS group had more residual mitral regurgitation (6 vs. 2), but the numbers were too small for statistical analysis.
Table 2. Major complications in the intensive care unit. Complication
Study group
Controls
p value*
Respiratory Arrhythmias PH crisis Mortality
10 4 0 0
5 2 2 1
Not Not Not Not
significant significant significant significant
*Fischer’s exact test. PH: pulmonary hypertensive.
Discussion The last few decades have shown a significant change in the approach to CHD surgery in children with DS. As the life expectancy and treatment for non-cardiovascular morbidity in DS patients has improved, it has became necessary and ethical to take care of their CHD effectively. Because the outcome of CHD surgery in general has been steadily improving due to refinements in surgical technique and perioperative care, it is possible to take up the challenge of cardiac surgery in DS children. The prevalence of DS in the US has increased by 31% (from 9 to 12 per 10,000 live births) in the last 3 decades.1 This means that the number of children with DS seeking cardiac care has risen in the recent past, and will continue to rise. With the current standard of pediatric cardiac care, it is important to see whether DS children have a different surgical outcome to non-DS patients in terms of ICU requirements, to predicted resource consumption in health care. Complete AVSD is the characteristic cardiac lesion in DS.2,3 However the prevalence of this lesion in DS seems to vary in different geographical regions of the world. In epidemiological studies in the United States and Europe, complete AVSD was found in 60% of patients.4,5 In Asia, isolated ventricular septal defect has been reported to be the most common defect, observed in approximately 40% of patients.6 In Latin America, secundum atrial septal defect was reported to be the most common lesion.7 In our series, AVSD contributed to only 28% of DS children undergoing surgery, with simpler lesions such as atrial septal defect,
168
Asian Cardiovascular & Thoracic Annals 21(2) Table 3. Surgical outcome of complete atrioventricular septal defect repair. Variable
Study group
Controls
p value*
Mortality Duration of ventilation (h) ICU stay (days) Additional inotropic support Complications Respiratory Arrhythmia Late redo surgery
0 68.2 46 7.9 4.0 7
0 37.4 29 5.7 5.5 5
0.0025 Not significant Not significant
4 2 0
1 1 1
Not significant Not significant Not significant
*Fischer’s exact test. ICU: intensive care unit.
ventricular septal defect, and patent ductus arteriosus together accounting for 50%. Fudge and colleagues8 recently reported the surgical outcome of DS patients, based on a US national database, compared to that of non-DS children; in this large series (n = 4350), there was no difference in mortality between the 2 groups, even though patients with DS were younger at surgery (median age 5.2 months). Duration of hospital stay was longer for atrial and ventricular septal defect closure and intracardiac repair of tetralogy of Fallot in DS children. In our series, we also observed no difference in mortality between the 2 groups. Median age at surgery was 10 months, and DS children had a significantly longer period of ventilation and ICU stay compared to non-DS children. These findings could be attributed to a larger proportion of patients with DS having preoperative risk factors and postoperative complications. Malec and colleagues9 also reported prolonged ventilation and longer duration of ICU stay in patients with DS. Respiratory complications and infections are known to play a significant role in morbidity and mortality in DS.10 Chronic upper airway obstruction, increased secretions and gastroesophageal reflux leading to chronic aspiration may be some of the contributing factors. Abnormalities in T lymphocyte maturation and function in DS patients predispose them to frequent infections.11 Fudge and colleagues8 also reported a higher incidence of respiratory and infectious complications in their study. Our study observed a trend towards a higher incidence of respiratory and infectious complications in DS, but it was not statistically significant. Several reports have noted lower mortality for AVSD in DS compared to non-DS children.8,12,13 It has been postulated that more favorable cardiac anatomic features, such as better atrioventricular valve morphology and fewer left-sided obstructive lesions, may be responsible for better outcomes in DS children
with AVSD. In the subgroup analysis of complete AVSD in our study, there was a significant difference in the mean duration of ventilation, while all other parameters were similar to those of non-AVSD surgery. Residual and progressive mitral regurgitation is a matter of major concern following AVSD surgery. Residual mitral regurgitation and redo surgery are more common after a non-DS AVSD repair.12 The observation in our study, where 6 patients in this category had 52þ mitral regurgitation (one requiring redo surgery), compared to only 2 with significant regurgitation in the DS group, supports this theory, but the numbers were too small for statistical analysis. Our series did not contain any patient undergoing Fontan track surgery. In view of the reported high mortality and morbidity of univentricular surgery in DS,8 the approach that we have followed is to avoid Fontan surgery in DS children in our resource-scarce scenario. Tucker and colleagues1 reported a higher incidence of postoperative complete heart block in DS children undergoing ventricular septal defect closure. A similar finding was also noted by Fudge and colleagues.8 In our series, there was no complete heart block in DS children; indeed, the only pacemaker implantation was performed in a non-DS patient for postoperative complete heart block following ventricular septal defect closure. This was a retrospective case-control study. The study design may have inherent statistical limitations that could affect conclusions with regard to significance. However, we concluded that simpler lesions outnumbered complete AVSD in this series, and DS children could be operated on with negligible mortality. There was a significantly longer duration of ventilation and ICU stay in such children, compared to non-DS patients, and a trend towards a higher incidence of respiratory complications. The intermediate-term functional status of DS children was comparable to that of non-DS children, with isolated instances of reintervention.
Lal et al. Acknowledgment The authors gratefully acknowledge the contribution of Dr Nagarajan Gurumani, MSc, PhD, in the statistical analysis of the study.
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Conflicts of interest statement None declared.
References 1. Shin M, Besser LM, Kucik JE, Lu C, Siffel C, Correa A, et al. Prevalence of Down syndrome among children and adolescents in 10 regions of the United States. Pediatrics 2009; 124: 1565–1571. 2. Tubman TR, Shields MD, Craig BG, Mulholland HC and Nevin NC. Congenital heart disease in Down’s syndrome: two-year prospective early screening study. BMJ 1991; 302: 1425–1427. 3. Laursen HB. Congenital heart disease in Down’s syndrome. Br Heart J 1976; 38: 32–38. 4. Mathew P, Moodie D, Sterba R, Murphy D, Rosenkranz E and Homa A. Long-term follow-up of children with Down syndrome with cardiac lesions. Clin Pediatr (Phila) 1990; 29: 569–574. 5. Figueroa JD, Magana BD, Hach J, Jimenez C and Urbina R. Heart malformations in children with Down syndrome. Rev Esp Cardiol 2003; 56: 894–895. 6. Jacobs EG, Leung MP and Karlberg J. Distribution of symptomatic congenital heart disease in Hong Kong. Pediatr Cardiol 2000; 21: 148–157.
169 7. Vida VL, Barnoya J, Larrazabal LA, Gaitan G, de Maria Garcia F and Castan˜eda AR. Congenital cardiac disease in children with Down’s syndrome in Guatemala. Cardiol Young 2005; 15: 286–290. 8. Fudge JC, Li S, Jagger J, O’Brain SM, Peterson ED, Jacob JP, et al. Congenital heart surgery outcomes in Down syndrome. Analysis of a national clinical database. Pediatrics 2010; 126: 315–322. 9. Malec E, Mroczek T, Pajak J, Januszewska K and Zdebska E. Results of surgical treatment of congenital heart defects in children with Down’s syndrome. Pediatr Cardiol 1999; 20: 351–354. 10. Yang Q, Rasmussen SA and Friedman JM. Mortality associated with Down’s syndrome in the USA from 1983 to 1997: a population-based study. Lancet 2002; 359: 1019–1025. 11. Kusters MA, Verstegen RH, Gemen EF and de Vries E. Intrinsic defect of the immune system in children with Down syndrome: a review. Clin Exp Immunol 2009; 156: 189–193. 12. Formigari R, Di Donato RM, Gargiulo G, Di Carlo D, Feltri C, Picchio FM, et al. Better surgical prognosis for patients with complete atrioventricular septal defect and Down’s syndrome. Ann Thorac Surg 2004; 78: 666–672. 13. Nisli K. Prevalence of congenital heart defect in patients with Down’s syndrome. J Pediatr (Rio J) 2009; 85: 377–378. 14. Tucker EM, Pyles LA, Bass JL and Moller JH. Permanent pacemaker for atrioventricular conduction block after operative repair of perimembranous ventricular septal defect. J Am Coll Cardiol 2007; 50: 1196–1200.
