PEDIATRICS Vol. 121 No. 3 March 2008, pp. 476-483 (doi:10.1542/10.1542/peds.2007-1282)
ARTICLE |
Neurodevelopmental Outcomes After Staged Palliation for Hypoplastic Left Heart Syndrome
Department of Pediatrics, Divisions of a Cardiology
d General Pediatrics
e Psychology
f Genetics
g Neurology
b Department of Anesthesia and Critical Care Medicine
h Department of Surgery, Division of Cardiothoracic Surgery, Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
c Department of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington
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ABSTRACT |
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 TOP ABSTRACT METHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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OBJECTIVE. The goal was to determine the relative effects of underlying genetic factors and current management strategies on neurodevelopmental disabilities among one-year old survivors of palliation for hypoplastic left heart syndrome.
METHODS. Children who underwent staged reconstruction for hypoplastic left heart syndrome and variants were assessed at 1 year of age by using a neuromuscular examination and the Bayley Scales of Infant Development II, which provide the Mental Development Index and the Psychomotor Development Index. The effects of perioperative, operative, and genetic variables on developmental scores were evaluated.
RESULTS. The median birth weight was 3.3 kg (range: 2.1–4.5 kg). Eight-three patients (94%) underwent multiple operations with cardiopulmonary bypass during the first year of life (median: 2 operations). Seven patients (8%) required extracorporeal membrane oxygenation. Twenty-five patients (28%) had a confirmed or suspected genetic syndrome. At 1 year of age, the neuromuscular examination results were abnormal or suspect for 57 patients (65%). The median Mental Development Index score was 90, and 10 patients (11%) had scores of <70 (2 SDs below the general population mean). The median Psychomotor Development Index score was 73, and 42 patients (48%) had scores of <70. In multivariate analyses, younger gestational age, the presence of a genetic syndrome, and the need for preoperative intubation had significant negative effects on neurodevelopmental outcomes. No association was found with operative factors, including duration of deep hypothermic circulatory arrest.
CONCLUSIONS. At 1 year of age, there was a significant incidence of neurodevelopmental disabilities in children with hypoplastic left heart syndrome and variants; motor scores were particularly concerning. Many children had suspected or confirmed genetic syndromes, which negatively affected neurodevelopmental outcomes. Surgical variables did not affect neurologic outcomes.
Key Words: developmental outcomes • hypoplastic left heart syndrome
Abbreviations: HLHS—hypoplastic left heart syndrome • DHCA—deep hypothermic circulatory arrest • CPB—cardiopulmonary bypass • MDI—Mental Development Index • PDI—Psychomotor Development Index • ECMO—extracorporeal membrane oxygenation • LOS—length of stay • S1R—stage 1 reconstruction • PVL—periventricular leukomalacia • mBTS—modified Blalock-Taussig shunt
Survival rates for patients undergoing stage 1 reconstruction (S1R) (the Norwood procedure) for hypoplastic left heart syndrome (HLHS) and variants have improved dramatically over the past decade.1–4 Prenatal diagnosis and improved surgical strategies and perioperative care are likely important contributors. Early reports revealed a concerning incidence of significant developmental problems in patients. More-recent studies of neurodevelopmental outcomes in patients with HLHS and variants demonstrated improving outcomes but continued evidence of developmental delays, compared with population normative values (Mahle et al5: 4 centers, n = 48; mean age: 12 years; mean full-scale IQ: 86; Mahle et al6: single center, n = 28; mean age: 9 years; mean full-scale IQ: 86; Goldberg et al7: single center, n = 51; mean age: 4.8 years; mean full-scale IQ: 93; Visconti et al8: single center, n = 29; age: 1 year; Mental Development Index [MDI]: 88; Psychomotor Development Index [PDI]: 75). However, patient numbers in those series were small, and comprehensive follow-up evaluation often is difficult. Neurologic compromise may begin in utero because of diminished cerebral blood flow, which has been shown to be associated with preoperative periventricular leukomalacia (PVL).9 Microcephaly is more frequent in patients with HLHS.10,11 Preoperative brain MRI demonstrates an increased frequency of ischemic lesions.12,13 Confirmed or suspected genetic syndromes are frequent in patients with HLHS. Because early surgical palliation is necessary for survival, identifying specific patient-related and preoperative risk factors for worsened neurodevelopmental outcomes can be difficult.
The primary aim of this study was to report the results of neurodevelopmental testing at 1 year of age in a large cohort of patients (n = 88) who underwent staged palliation for HLHS and variants. The secondary aim was to identify risk factors for compromised outcomes.
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METHODS |
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Patient Population
This study is a secondary analysis of a prospective trial assessing the effects of a genetic polymorphism on neurodevelopmental outcomes.14 Informed consent was obtained from the parents or legal guardians. The study was approved by our institutional review board.
Patients born with HLHS or variants between April 1998 and March 2003 were eligible. Entry criteria included all patients with single-ventricle physiologic features and systemic outflow obstruction undergoing staged palliation. Exclusion criteria before surgical intervention included (1) multiple congenital anomalies, (2) recognizable chromosomal or phenotypic syndrome at birth (patients with 22q11 deletion were included in the study), and (3) non–English language primarily spoken in the home. Patients who were diagnosed as having chromosomal or phenotypic syndromes after their initial operation or at the time of 1-year neurodevelopmental testing were included. Anatomic diagnoses included (1) HLHS with a combination of mitral stenosis or atresia and aortic stenosis or atresia and (2) variants including single ventricles (right or left) with systemic outflow obstruction.
Five surgeons performed S1R during the study period. Patients were cared for by a dedicated group of cardiac anesthesiologists and recovered in a dedicated cardiac ICU. Surgical strategies included (1) deep hypothermic circulatory arrest (DHCA) for all patients with a goal nasopharyngeal temperature of 18°C, (2) 
-stat blood gas management, and (3) use of modified ultrafiltration. The right ventricle-pulmonary artery conduit was introduced in March 2002. Before that time, the modified Blalock-Taussig shunt (mBTS) was the shunt of preference, with a central shunt being used rarely if there was inadequate pulmonary blood flow with the mBTS. After March 2002, the choice of shunt was at the discretion of the surgeon, with 70% of shunts being the mBTS. Routine postoperative infusions were fentanyl (1–2 µg/kg per hour), pancuronium (the first postoperative night; 0.05–0.1 mg/kg per hour), dopamine (3–5 µg/kg per minute), and milrinone (0.25–1 µg/kg per minute). Delayed sternal closure was not routine, and extracorporeal membrane oxygenation (ECMO) was reserved for failure to separate from cardiopulmonary bypass (CPB), cardiac arrest, or near-arrest. Surgical data are described for the S1R and for all operations requiring CPB during the first year of life. Length of stay (LOS) was determined by the time of discharge or transfer. Data included in the risk factor analyses are listed in the Appendix.
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Neurodevelopmental Examination
The neurodevelopmental evaluation was described previously.14 Children were evaluated at 1 year (±2 weeks; adjusted for prematurity), by using the Bayley Scales of Infant Development II. These scales include the PDI, which assesses gross motor and fine motor skills, and the MDI, which assesses memory, problem-solving, number concepts, generalization, vocalization, language, and social skills. The mean score for both tests is 100, with a SD of 15; the lowest assigned score was 50. A score of <70 is >2 SDs below the mean. The neuromuscular examination results (active tone, passive tone, reflexes, gross motor abilities, and fine motor abilities) were classified as normal if no abnormalities affecting motor skills were noted, suspect if a moderate degree of abnormality was noted, and abnormal if functionally significant abnormalities of tone, reflexes, or motor skills were present. At the 1-year testing, a genetic specialist evaluated every patient. Chromosomal and microdeletion testing was performed when possible. The genetic evaluation results were classified as normal, suspect (evidence of a genetic syndrome was present but chromosomal confirmation was not possible), or abnormal (a specific genetic diagnosis was confirmed). The genetic specialist was blinded with respect to the results of the developmental testing. The familial socioeconomic status was assessed through parental report, by using the Hollingshead scale, during the visit at 1 year of age. Ethnicity was classified as Asian/Pacific Islander, black, Hispanic, Native American, other, or white, as reported by the parent.
Statistical Analyses
Continuous variables were expressed as mean ± SD or median (with range). Dichotomous and categorical variables were presented as proportions. To identify risk factors for negative neurodevelopmental outcomes, the variables listed in the Appendix were tested in a univariate manner for association with MDI, PDI, and neuromuscular examination results by using linear and logistic regression analyses. Categorical data were coded as dummy variables for the regression analyses, with the most common category being used as the reference group, and the overall model P values are reported. After univariate analyses, variables associated with an outcome with P < .1 in the univariate models were included in multivariate analyses of MDI, PDI, and neuromuscular examination results. Only variables that were associated with an outcome were included in the multivariate analysis for that outcome. In the multivariate analyses, we considered forward and backward stepwise regression models, with the most parsimonious set of significant predictors being reported in the final model for each outcome. All analyses used SPSS 10.0 for Windows (SPSS, Chicago, IL) and the R statistical software environment (R Project for Statistical Computing, Vuebba, Austria).
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RESULTS |
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Between April 1998 and March 2003, 161 patients undergoing S1R for HLHS and variants were enrolled, with a hospital survival rate of 148 (92%). There were 15 deaths (9%) after hospital discharge and before 1 year of age. Of the 133 survivors, 88 (66%) returned for 1-year neurodevelopmental evaluations and constitute the study population. Anatomic subtypes of the study group are shown in Table 1. The preoperative and intraoperative statistics comparing the study group with (1) the nonsurvivors and (2) the enrolled patients who survived to 1 year but did not return are shown in Table 2. Delayed sternal closure was used for 38 patients (23%), and ECMO was needed for 13 patients (8%). There was no difference in the distance of travel between the patients who died (median: 102 miles; range: 1.8–1401 miles) and the patients who returned for 1-year testing (median: 83 miles; range: 2.9–1041 miles; P = .14). However, the travel distance was greater for surviving patients who did not return for testing (median: 124 miles; range: 2.9–4910 miles; P = .012). No research funds were available to support travel.
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The study subjects who underwent 1-year neurodevelopmental testing were primarily of the white race and had a significantly older gestational age, higher birth weight, and larger birth head circumference than did those who did not return or did not survive. In addition, the study population had a shorter postoperative LOS, compared with survivors who did not return for testing. However, all survivors who had been supported with ECMO (n = 7) returned for testing.
At the time of neurodevelopmental testing, the median age was 1.01 years (range: 0.95–1.08 years), the median weight was 8.5 kg (range: 6.1–11 kg), and the median head circumference was 45.8 cm (range: 40.5–49 cm). At the time of 1-year follow-up evaluation, a genetic syndrome or chromosomal abnormality was found or suspected for 31 patients (35%). Chromosomal abnormalities in those tested included balanced translocation 13:14 (1 case), X-linked immunodeficiency (1 case), 11p deletion (1 case), and partial Turner syndrome (1 case). Diagnosed syndromes included Kabuki syndrome (1 case) and syndromic but undefined (3 cases). Patients with definite or suspected genetic conditions were not significantly different with respect to birth weight, birth head circumference, gestational age, preoperative intubation, use of ECMO, use of delayed sternal closure, and length of DHCA or CPB. They did, however, have a longer postoperative LOS after their S1R (22 ± 19 vs 13 ± 9.5 days; P = .02).
Abnormal or suspect neuromuscular examination results were found for 56 patients (64%), with no significant difference between those without genetic syndromes (n = 35; 59%) and those with known (n = 6; 100%; P = .08) or suspected (n = 13; 72%; P = .41) genetic syndromes. In multivariate analyses, patients with a longer postoperative LOS for the S1R were more likely to have abnormal or suspect neuromuscular examination results (β = 0.091; 95% confidence interval: 0.02–0.21; SE: 0.046; P = .05), and patients of black race were less likely to have abnormal or suspect neuromuscular examination results (β = –2.57; 95% confidence interval: –5.21 to –0.73; SE: 1.07; P = .017).
For the overall study group, the median MDI score was 90 (range: 50–129), and 10 (11%) had scores of <70 (2 SDs below the mean for the general population). The median PDI score was 73 (range: 50–117), and 42 (48%) had scores of <70 (Fig 1). Significant univariate and multivariate risk factors for lower scores are shown in Table 3. Multivariate risk factors for lower MDI score were younger gestational age (P = .011), abnormal (P = .001) or suspect (P = .011) genetic evaluation results at 1 year of age, preoperative endotracheal intubation (P = .002), and younger gestational age (P = .011). Multivariate risk factors for lower PDI score were abnormal (P = .005) or suspect (P = .011) genetic evaluation results at 1 year of age and preoperative intubation (0.002) (Fig 2).
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Patients were evenly divided between earlier (April 1998 through January 2001; n = 44) and later (January 2001 through March 2003; n = 44) eras of S1R. There were no significant differences between the eras of surgery in the perioperative and surgical parameters measured, with the following exceptions: (1) lower hematocrit levels on CPB in the earlier era (26 ± 2.8% vs 30.7 ± 3.3%; P < .0001), (2) more-frequent use of preoperative intubation in the earlier era (26 of 44 patients [59%] vs 14 of 44 patients [32%]; P = .018), (3) longer preoperative LOS in the earlier era (2.9 ± 1.7 days vs 2.0 ± 1.2 days; P = .004), and (4) more-frequent diagnosis of HLHS in the later era (29 of 44 patients [66%] vs 39 of 44 patients [88%]; P = .02). However, there were trends in the later era toward improved MDI scores (85.2 ± 17.0 vs 91.5 ± 15.6; P = .079) and PDI scores (67.2 ± 17 vs 73.7 ± 18; P = .084).
Twenty-eight of the 89 patients who returned for testing underwent their initial palliative surgery after March 1, 2002, when the right ventricle-pulmonary artery conduit was introduced; the right ventricle-pulmonary artery conduit was used for 10 patients and the mBTS for 18 patients. There was no significant difference in MDI (right ventricle-pulmonary artery conduit: median: 94.5; range: 77-105; mBTS: median: 97.5; range: 64-129; P = .53) and PDI (right ventricle-pulmonary artery conduit: median: 87; range: 69-105; mBTS: median: 87; range: 55-117; P = .73) scores between shunt types.
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DISCUSSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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Reported risk factors for death in patients with HLHS include low birth weight,1–4,15,16 preoperative shock,2 single right ventricle (compared with left ventricle),4 obstruction to pulmonary venous return,2 severe ventricular dysfunction,2,4,16 genetic syndrome,3 and size of the ascending aorta.1,4 The current study identified similar patient-specific risk factors (gestational age, genetic syndromes, and ethnicity), rather than operative variables, as risk factors for worse neurodevelopmental outcomes. Although these patient-related risk factors cannot be modified, there exist surgical and perioperative management strategies that likely affect long-term morbidities, including suboptimal neurologic outcomes.
Studies showed that neonates with HLHS have evidence of preoperative factors that likely compromise neurologic outcomes. Dent et al12 performed preoperative brain MRI in term infants (n = 22) without hemodynamic decompensation or genetic syndromes and found that 23% of patients had ischemic lesions or areas of small hemorrhage and only 50% of patients had completely normal study results. Metabolic acidosis (base deficit: median: 4 mmol/L; range: 1–7.5) was the only identified preoperative risk factor to affect MRI findings (P = .024). These preoperative MRI findings are similar to those reported previously for newborns with complex congenital heart disease.13 Microcephaly is more common in patients with HLHS, compared with both normal infants and other newborns with complex heart disease, and may result from abnormal in utero physiologic features and cerebral blood flow.10,11 Preoperative cerebral blood flow, as measured by MRI, is decreased9 and is associated with increased incidence of PVL.
Early postoperative neurologic evaluations have detected abnormalities, but the impact on long-term neurologic outcomes remains uncertain. Postoperative brain MRI demonstrated new or enlarged ischemic injury, including PVL, in 73% of patients with HLHS (11 of 15 patients).12 Operative variables were not found to affect the incidence of MRI abnormalities in this small series. Prolonged (chosen as >3 cumulative hours) low (<45%) cerebral oxygen saturation, as measured with a near-infrared spectroscopy surface probe, was associated with MRI abnormalities.12 Postoperative hypoxemia and low diastolic blood pressure were shown to be associated with an increased incidence of PVL on postoperative MRI scans.17 Authors at the University of Michigan compared MRI results and neurodevelopmental scores in patients after Fontan palliation (n = 29; age of testing: 4.8 years) and were unable to show a significant correlation between ischemia or infarction and lower test scores.7
Several small series reported neurodevelopmental follow-up data for patients with HLHS. Some of those series examined perioperative factors to determine how they affected outcomes. Investigators at Children's Hospital of Wisconsin found that lower systemic venous oxygen saturation in the immediate postoperative period negatively affected neurodevelopmental outcomes (n = 13; mean age at testing: 4.5 years).18 Investigators at Boston Children's Hospital studied patients treated during their S1R with DHCA (44.3 ± 15 minutes), compared with regional low-flow perfusion with a shorter period of DHCA (23.5 ± 13 minutes), and found no significance in neurodevelopmental outcomes (n = 29; age at testing: 1 year). They did find that intraoperative temperature of <16°C and birth order (younger sibling) negatively affected MDI score and older age at S1R and birth order (younger sibling) negatively affected PDI score.8 Using a prospective, randomized strategy, investigators at the University of Michigan also compared the use of DHCA (41 ± 10 minutes) with the use of regional cerebral perfusion (mean DHCA time: 5.7 minutes) and also found no statistical difference in developmental testing results (n = 50; age at testing: 1 year).19 Similarly, they found the PDI (score: 77 ± 20) to be significantly more affected than the MDI (92 ± 21; P < .0001). They found no statistical difference between patients in the regional cerebral perfusion group (PDI: 74 ± 20; MDI: 88.9 ± 22) and patients in the DHCA group (PDI: 79.6 ± 21; P = .34; MDI: 94.1 ± 20; P = .39). The MDI and PDI scores in that study were very similar to those in the current study. Mahle et al5 evaluated survivors with HLHS from 4 centers, comparing the S1R with primary heart transplant (n = 48; age at testing: 12 years), and found that surgical approach was not associated with neurodevelopmental test scores. Multivariate analyses of many patient- and procedure-related risk factors found only longer LOS to affect test scores negatively. Neurodevelopmental testing after repair or palliation of neonatal heart disease demonstrated that clinical7 but not electrographic20 seizures affected neurodevelopmental outcomes.
In this study, we report the 1-year neurodevelopmental testing results for a significantly larger cohort of patients (n = 88) than reported previously, with a secondary aim of identifying patient-related and perioperative risk factors for compromised outcomes. Perioperative information was collected prospectively. In addition, perioperative and surgical data included all operations before the age of testing in the risk analyses. Similar to the smaller series of patients with HLHS reported from Boston Children's Hospital8 and from the University of Michigan,19 we found the PDI to be more seriously affected than the MDI, a finding that is consistent across many other diagnostic groups studied to date. Despite a fairly exhaustive list of patient-related and perioperative risk factors, multivariate analyses identified few risk factors for worsened neurodevelopmental testing results. The neuromuscular examination results were worse for patients with a longer S1R LOS and improved for patients of black race. These findings of higher motor scores for black patients, compared with other ethnic groups, have been reported previously.21 Suspected or confirmed genetic syndrome and earlier gestational age affected PDI scores negatively. These same risk factors, in addition to the need for preoperative intubation, affected MDI scores negatively. Interestingly, although there was a wide range of CPB and DHCA times, operative variables, including the duration of DHCA, were not associated with better or worse outcomes. Most concerning was the subgroup with 
2 statistically significant risk factors, in which no patient had a PDI score of >100 and only 3 patients had MDI scores of >100 (mean for normal populations). In fact, in the entire cohort, only 2 patients had both MDI and PDI scores of >100.
Comparisons of the earlier (1998–2001) and later (2001–2003) eras of surgery revealed only 2 expected differences in perioperative and surgical parameters, reflecting changes in practice. There was a higher hematocrit level during CPB and fewer preoperative endotracheal intubations in the later era. The change in hematocrit levels reflected a response to the intraoperative hemodilution study performed at Boston Children's Hospital (1996–2000), which demonstrated worsened outcome measures at lower hematocrit levels.22 In the multivariate analyses, however, higher hematocrit levels were not associated with improved outcomes. The increased incidence of prenatal diagnosis, use of lower doses of prostaglandin, and a trend away from intubation for transport have contributed to the decreased incidence of preoperative intubations. Other than the identified change in hematocrit strategy between the earlier and later eras, the operative management remained fairly stable. Perioperative management, in contrast, reflected many changes, including less frequent use of preoperative hypoxic gas mixtures, decreasing dosage of postoperative fentanyl infusions, less use of postoperative infusions of muscle relaxants, and more liberal use of postoperative oxygen therapy. Many of these factors in research models have been shown to affect neurologic outcomes. One must consider that perioperative management and perhaps postdischarge interventional factors play more important roles in determining neurologic outcomes than do surgical strategies. Our finding of improved neurologic outcomes, measured as the MDI and PDI of the Bayley scales, during the time course of the study period reinforces caution regarding the use of historical control data.
Although our study population nearly doubles the next largest trial, risk factor analyses remain limited by statistical power. In addition, risk factor analyses are limited to the extensive but most likely incomplete list of factors measured prospectively in this trial. Because of the tertiary referral patterns, a substantial number of patients were unable to participate in the neurodevelopmental follow-up evaluation. Patients who returned for evaluation were disproportionately of white race, had greater gestational age and birth weight, and had shorter postoperative LOS. Therefore, the study population might have had better neurodevelopmental outcome scores than the entire cohort, had it been tested. The socioeconomic status was determined at the 1-year follow-up evaluation, which limited our ability to compare evaluated and nonevaluated patients. Our designation of suspected or confirmed genetic syndrome was determined through evaluation by a geneticist at 1 year of age. Genetic studies were ordered only when clinically indicated. Ideally, genetic testing of the entire cohort, with a combination of complete chromosome, telomere, and comparative genomic hybridization testing, might have improved our accuracy in identification of genetic syndromes. Finally, 1-year neurodevelopmental evaluations have limited predictive validity for longer-term neurologic and developmental outcomes. The cohort currently is undergoing developmental testing at 4 years of age.
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CONCLUSIONS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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Patients with HLHS demonstrate deficiencies in 1-year neurodevelopmental testing results, with motor scores (PDI) being more affected than cognitive scores (MDI). Multivariate analyses identified suspected or confirmed genetic syndrome and younger gestational age as risk factors negatively affecting outcomes, with no identifiable impact of intraopertative variables such as duration of DHCA or CPB. However, even among patients with no more than 1 significant risk factor, only 3 patients had PDI scores above the mean for normal control subjects (score: 100) and only 2 patients had both MDI and PDI scores of >100. Later era of surgery trended toward positively affecting both MDI and PDI scores. With little change in operative strategies, the lack of impact of intraoperative support techniques on 1-year outcomes suggests that future research should continue to focus on the role of perioperative management and postdischarge early interventions. Longer-term developmental follow-up evaluation of these patients is of utmost importance and currently is underway in this patient population. In addition, continued investigation to identify modifiable risk factors in this high-risk group of infants must be supported.
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ACKNOWLEDGMENTS |
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This work was supported by an American Heart Association national grant-in-aid (grant 9950480N, to Dr Gaynor), the Pew Biomedical Scholar Program (Dr Jarvik), and the Fannie E. Rippel Foundation (Dr Gaynor).
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FOOTNOTES |
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Accepted Aug 10, 2007.
Address correspondence to Sarah Tabbutt, MD, PhD, Cardiac Intensive Care Unit, Cardiac Center, Children's Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104. E-mail: tabbutt{at}email.chop.edu
The authors have indicated they have no financial relationships relevant to this article to disclose.
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REFERENCES |
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- Tweddell JS, Hoffman GM, Mussatto KA, et al. Improved survival of patients undergoing palliation of hypoplastic left heart syndrome: lessons learned from 115 consecutive patients. Circulation.2002; 106 (12 suppl 1):I82 –I89[Web of Science][Medline]
- Tabbutt S, Dominguez TE, Ravishankar C, et al. Outcomes after the stage 1 reconstruction comparing the right ventricular to pulmonary artery conduit with the modified Blalock-Taussig shunt.
Ann Thorac Surg.2005; 80
(5):1582
–1591
[Abstract/Free Full Text] - Stasik CN, Goldberg CS, Bove EL, Devaney EJ, Ohye RG. Current outcomes and risk factors for the Norwood procedure.
J Thorac Cardiovasc Surg.2006; 131
(2):412
–417
[Abstract/Free Full Text] - McGuirk SP, Stickley J, Griselli M, et al. Risk assessment and early outcome following the Norwood procedure for hypoplastic left heart syndrome.
Eur J Cardiothorac Surg.2006; 29
(5):675
–681
[Abstract/Free Full Text] - Mahle WT, Visconti KJ, Freier C, et al. Relationship of surgical approach to neurodevelopmental outcomes in hypoplastic left heart syndrome. Pediatrics.2006; 117 (1). Available at: www.pediatrics.org/cgi/content/full/117/1/e90
- Mahle WT, Clancy RR, Moss EM, Gerdes M, Jobes DR, Wernovsky G. Neurodevelopmental outcome and lifestyle assessment in school-aged and adolescent children with hypoplastic left heart syndrome.
Pediatrics.2000; 105
(5):1082
–1089
[Abstract/Free Full Text] - Goldberg CS, Schwartz EM, Brunberg JA, et al. Neurodevelopmental outcome of patients after the Fontan operation: a comparison between children with hypoplastic left heart syndrome and other functional single ventricle lesions. J Pediatr.2000; 137 (5):646 –652[CrossRef][Web of Science][Medline]
- Visconti KJ, Rimmer D, Gauvreau K, et al. Regional low-flow perfusion versus circulatory arrest in neonates: one-year neurodevelopmental outcome.
Ann Thorac Surg.2006; 82
(6):2207
–2213
[Abstract/Free Full Text] - Licht DJ, Wang J, Silvestre DW, et al. Preoperative cerebral blood flow is diminished in neonates with severe congenital heart defects.
J Thorac Cardiovasc Surg.2004; 128
(6):841
–849
[Abstract/Free Full Text] - Rosenthal GL. Patterns of prenatal growth among infants with cardiovascular malformations: possible fetal hemodynamic effects.
Am J Epidemiol.1996; 143
(5):505
–513
[Abstract/Free Full Text] - Shillingford AJ, Ittenbach RF, Marino BS, et al. Aortic morphometry and microcephaly in hypoplastic left heart syndrome. Cardiol Young.2007; 17 (2):189 –195[CrossRef][Medline]
- Dent CL, Spaeth JP, Jones BV, et al. Brain magnetic resonance imaging abnormalities after the Norwood procedure using regional cerebral perfusion.
J Thorac Cardiovasc Surg.2006; 131
(1):190
–197
[Abstract/Free Full Text] - Mahle WT, Tavani F, Zimmerman RA, et al. An MRI study of neurological injury before and after congenital heart surgery. Circulation.2002; 106 (suppl I):109 –114
- Gaynor JW, Gerdes M, Zackai EH, et al. Apolipoprotein E genotype and neurodevelopmental sequelae of infant cardiac surgery.
J Thorac Cardiovasc Surg.2003; 126
(6):1736
–1745
[Abstract/Free Full Text] - Artrip JH, Campbell DN, Ivy DD, et al. Birth weight and complexity are significant factors for the management of hypoplastic left heart syndrome.
Ann Thorac Surg.2006; 82
(4):1252
–1259
[Abstract/Free Full Text] - Nilsson B, Mellander M, Sudow G, Berggren H. Results of staged palliation for hypoplastic left heart syndrome: a complete population based series. Acta Paediatr.2006; 95 (12):1594 –1600[CrossRef][Medline]
- Gaynor JW, Jarvik GP, Bernbaum J, et al. The relationship of postoperative electrographic seizures to neurodevelopmental outcome at 1 year of age after neonatal and infant cardiac surgery.
J Thorac Cardiovasc Surg.2006; 131
(1):181
–189
[Abstract/Free Full Text] - Hoffman GM, Mussatto KA, Brosig CL, et al. Systemic venous oxygen saturation after the Norwood procedure and childhood neurodevelopmental outcome.
J Thorac Cardiovasc Surg.2005; 130
(4):1094
–1100
[Abstract/Free Full Text] - Goldberg CS, Bove EL, Devaney EJ, et al. A randomized clinical trial of regional cerebral perfusion versus deep hypothermic circulatory arrest: outcome for infants with functional single ventricle.
J Thorac Cardiovasc Surg.2007; 133
(4):880
–887
[Abstract/Free Full Text] - Galli KK, Zimmerman RA, Jarvik GP, et al. Periventricular leukomalacia is common after neonatal cardiac surgery.
J Thorac Cardiovasc Surg.2004; 127
(3):692
–704
[Abstract/Free Full Text] - Bayley N. Comparisons of mental and motor test-scores for ages 1–15 months by sex, birth-order, race, geographical location and education of parents. Child Dev.1965; 36 (2):379 –411[CrossRef][Web of Science][Medline]
- Jonas RA, Wypij D, Roth SJ, et al. The influence of hemodilution on outcome after hypothermic cardiopulmonary bypass: results of a randomized trial in infants. J Thorac Cardiovasc Surg.2003; 126 (6):1763 –1774
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 R. R. Thiagarajan Developmental Outcomes After Surgery for Hypoplastic Left Heart AAP Grand Rounds, July 1, 2008; 20(1): 6 - 7. [Full Text] [PDF]
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 M. R. Mercurio, S. M. Peterec, and B. Weeks Hypoplastic Left Heart Syndrome, Extreme Prematurity, Comfort Care Only, and the Principle of Justice Pediatrics, July 1, 2008; 122(1): 186 - 189. [Full Text] [PDF]
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