Objective. To assess intellect and adaptive behavior in children with hypoplastic left heart syndrome (HLHS) who had undergone at least two surgical stages of the Norwood procedure.
Methods. Fourteen children with HLHS >3 years of age participated in the study. The patients underwent intelligence quotient (IQ) testing, and their parents were interviewed regarding their children's adaptive behavior. Results were compared with those of 10 family controls. Outcomes were studied for possible correlation with perioperative variables.
Results. Among the HLHS patients, the median scores for full scale IQ and adaptive behavior were 88 and 91, respectively (normal = 100 ± 15). One child met criteria for mental retardation. Family controls scored generally higher than did HLHS patients, but only differences in adaptive behavior were statistically significant. A negative correlation was found between stage I circulatory arrest time and full scale IQ.
Conclusions. Children with HLHS most often function in the low-normal range of intelligence and adaptive behavior. A prolonged circulatory arrest time may result in decreased intellectual function.
- HLHS =
- hypoplastic left heart syndrome •
- WPPSI-R =
- Wechsler Preschool and Primary Scale of Intelligence–Revised •
- IQ =
- intelligence quotient •
- PPVT =
- Peabody Picture Vocabulary Test •
- VMI =
- Beery Visual Motor Integration Test •
- VABS =
- Vineland Adaptive Behavior Scales •
- CA =
- circulatory arrest •
- CPB =
- cardiopulmonary bypass
Hypoplastic left heart syndrome (HLHS) is a congenital defect in which the left ventricle and aortic arch are underdeveloped or atretic, not allowing cardiac output from the left heart. Without surgery, infants with HLHS rarely survive beyond the first month of life.1 First described in 1980, the staged Norwood procedure has been an increasingly successful surgical approach for these patients.2 Ultimately, after a series of operations, the right ventricle functions as the systemic ventricle pumping into a reconstructed aortic arch, and pulmonary blood flow is achieved passively through a Fontan-type circulation. We and others have reported a 5-year actuarial survival exceeding 60%.3 ,4
Despite the improvement in survival, little is known regarding the intellectual and functional capabilities of these children. The effects of chronic cyanosis, multiple cardiac operations, and the known incidence of congenital and acquired brain abnormalities in association with HLHS5 ,6 increase the possibilities for intellectual deficit. One series that addressed intellectual outcome after the Norwood operation performed at various institutions found a high incidence of major developmental disabilities.7 The purpose of this study was to examine the intelligence and adaptive behavior of HLHS patients who had undergone the Norwood procedure at a single institution with uniform protocols and surgical technique.
All patients with HLHS, 3 years of age and older, who underwent at least two stages of the Norwood procedure at our institution were considered eligible for participation in the study. All operations were performed between January 1990 and January 1996. Total circulatory arrest (CA) (with a core body temperature of 18°C) was used for the first operation. All surgical procedures involved cardiopulmonary bypass (CPB) at a temperature of 24°C.
Each of the 14 eligible HLHS patients were successfully contacted, and each family agreed to at least partial developmental evaluation. Seventeen younger patients were not yet eligible for inclusion in the study. Informed consent was obtained before testing. There were 8 males and 6 females. The mean age at the time of testing was 4.4 years (range, 3.2–6.0 years). The mean interval between the most recent operation and developmental testing was 33 months (range, 3–61 months).
The average age at the first operation was 8 days. The mean CA and CPB times during stage I were 56 minutes and 188 minutes, respectively (Table 1). Three patients (patients 3, 8, and 14) experienced low cardiac output and evidence of hepatic or renal injury at initial presentation (defined by serum transaminases greater than 200 U/L or serum creatinine greater than 1.5 mg/dL [132.6 micromoles/L]). None of the patients were diagnosed prenatally. All abnormal laboratory findings had improved before surgery. The average length of stay during the initial hospitalization was 25 days (range, 11–42 days). No patient was known to have preoperative neurologic deficits. Two patients experienced seizures limited to the immediate postoperative period after stage I (patients 4 and 5). There were no central nervous system symptoms or neurologic deficits on physical examination after the second or third stage. No patient was on anticonvulsant therapy at the time of developmental evaluation. Average ages at times of second and third operations were 9.3 and 24.3 months, respectively. These ages reflect usual institutional timing for these operations.3 Ten patients had completed the Norwood procedure and had Fontan-type circulations. Four patients each were awaiting one more planned operation (patients 1, 2, 9, and 11).
A control group of 10 children included siblings (n = 9) and a first cousin (n = 1). The average age of this group was 5.7 years (range, 3.1–9.1 years). There were 4 males and 6 females (Table 1).
It is institutional policy to obtain neuroimaging studies of the brain, consisting of either computed tomography or magnetic resonance imaging, in all newborns with HLHS. This was not always possible, however, because of surgical timing. Neuroimaging was performed in 7 of the 14 HLHS patients. Three children (patients 4, 8, and 11) were found to have ischemic changes or infarcts (2 before the Norwood I and 1 after surgery). Another infant (patient 2) had cerebral atrophy (noted postoperatively). Three studies (patients 1, 6, and 7) were interpreted as normal (1 preoperatively, 2 postoperatively). Five infants underwent electroencephalograms (patients 2, 3, 4, 5, and 8). Four of the studies exhibited a mild degree of diffuse cerebral dysfunction. One study was interpreted as normal (patient 2). None of the controls underwent neuroimaging. Chromosomal analyses were not performed.
Methods of Evaluation
The following measures were used:
The Wechsler Preschool and Primary Scale of Intelligence-Revised, (WPPSI-R), which provides a full scale intelligence quotient (IQ), comprised of a verbal IQ and performance IQ.
The Peabody Picture Vocabulary Test (PPVT), which evaluates single word comprehension as an estimate of verbal IQ.
The Beery Visual Motor Integration Test (VMI), which measures skills in copying and construction as an estimate of performance IQ. Because of the lack of standardized scoring of the VMI <4 years of age, those patients between 3 and 4 years (3 HLHS patients and 1 control) were scored as 4-year-olds.
The Vineland Adaptive Behavior Scales (VABS), obtained through parent interviews, which provides information regarding adaptive behavior. An overall score was compiled, as well as scores of individual subsets, including skills of daily living, communication, social interactions, and motor capabilities.
Individual scores on each measure were compared with age-appropriate values (normal = 100 ± 15).8 Patients with scores more than two standard deviations below the mean were considered significantly impaired.
Twelve of the 14 patients completed the WPPSI-R, PPVT, and VMI. Two patients were unable to participate: 1 child lived at too great a distance to come for the evaluation and 1 patient did not speak English. The VABS were completed for each of the 14 children in the group.
The WPPSI-R was not administered to the controls. Seven of the 10 controls participated in the PPVT. Six children completed the VMI. The VABS were completed for all 10 controls.
Performances of the HLHS patients in the PPVT, VMI, and VABS were compared with those of the paired family controls utilizing the pairedt test. Patients without controls were not included in this comparison.
Risk Factor Analysis
Several factors were evaluated as possible contributors to intellectual and behavioral outcome. These included age at testing, number of operations completed, operative age at time of the first surgical stage, stage 1 CPB time, and stage 1 CA time. Scores of the HLHS patients in the WPPSI-R and VABS were analyzed for possible correlation with the above variables using Pearson correlation analyses.
Standardized IQ scores in the HLHS patients, as obtained through the WPPSI-R, are shown in Table 2. The median full scale IQ was 88, with median scores in performance IQ and verbal IQ of 83 and 91, respectively. Seven children had full-scale IQ scores of 85 or more. Three patients had scores between 70 and 84. Two patients scored <70 (greater than two standard deviations below the normal average). The 4 patients with the lowest full-scale IQ scores each had abnormalities seen on brain imaging and/or electroencephalography (patients 2, 4, 5, and 11).
The mean standardized VMI and PPVT scores were 82 ± 16 and 84 ± 12, respectively. The mean VABS was 91 ± 20. Among the subsets of VABS, social skills was relatively strong (median score of 103). The weakest subset for the HLHS patients was motor skills (median score of 85).
One of the 12 patients met diagnostic criteria for mental retardation (both full-scale IQ and VABS <70).8 Two had mixed scores (one test >70 and 1 test <70). Nine of the 12 children scored >70 in both full- scale IQ and VABS.
Mean standardized VMI and PPVT scores for the control group were 103 ± 13 and 99 ± 10, respectively. These scores are within the range expected for normal children. The mean scores in adaptive behavior were also within the normal range: 107 ± 22.
Comparisons between the HLHS and control groups are shown in Tables 3 and 4. The HLHS group had lower mean scores in each of the tests. The differences between the 2 groups in intelligence testing (VMI and PPVT) did not reach statistical significance. There was a statistically significant difference, however, in VABS, which measures skills in adaptive behavior (P = .025). Scores for patients and controls in behavioral subsets of VABS are shown in Fig 1. The children with HLHS scored lower than the controls in each of the areas tested, with the greatest discrepancy seen in motor skills.
Risk Factor Analysis
There was no correlation between the intellectual measures studied and CPB time, operative age, number of operations, or age at testing. CA time, however, did correlate negatively with full scale IQ (r = −0.68, P = .014). This was because of the relatively strong negative correlation with performance IQ (r = −0.77, P = .004) (Fig 2). CA time did not correlate with verbal IQ (r = −0.47, P = .12) (Fig 3).
Knowledge of the neurodevelopmental outlook for patients with HLHS may be an important aspect of the early decision making process for families, because no surgical intervention can be an option offered to infants with this condition.9–11 Data on intellectual outcome also allows for a more complete picture of long-term expectations for surgical survivors. There are multiple studies in the literature documenting intellectual deficits in children with chronic cyanosis who had or had not undergone cardiac surgery.12–14 However, there is only a single report in the literature specifically dealing with neurodevelopment after the Norwood procedure in children with HLHS.7 In that article, Rogers and associates7 describe a generally unfavorable outcome, with 7 of 11 children having “major developmental disabilities” and at least moderate mental retardation. Only 1 of the 11 children was normal in both cognition and motor skills.
Our study shows a somewhat more encouraging outcome. We found that 10 of 12 children age 3 to 6 years with HLHS had full scale IQs of 70 or more, indicating at least low-average intelligence. Of the 2 patients with full scale IQ scores <70, 1 also had an adaptive behavior score <70, meeting criteria for mental retardation. The HLHS patients scored lower on average than matched family controls in each of the tests performed, but only the difference in adaptive behavior reached statistical significance.
There are several important differences in the patient population in our group as compared with that of Rogers et al7: all operations in the present study were performed at a single institution, our patients with HLHS had a higher overall survival rate and were older when studied. In addition, the present study contains a sibling control group. Limitations of both reports include small sample size, retrospective rather than prospective longitudinal study design, lack of neuroimaging in each of the patients, and lack of chromosomal analyses.
Despite the more optimistic score results in this study, the children with HLHS did not perform as well as their peers. There are several possible explanations for this. First, the diagnosis of HLHS can be associated with chromosomal anomalies, some of which are not yet recognized, which may cause cognitive impairment.15 ,16 Our patients did not have distinct dysmorphology suggestive of any underlying chromosomal disorder. In addition, congenital brain anomalies, including microcephaly, abnormal cortical mantle formation, and agenesis of the corpus collosum have been reported to be common in newborns with isolated HLHS.5 In this report, computed tomography and magnetic resonance imaging studies in 7 patients did not disclose congenital brain abnormalities, although had neuroimaging been performed on the other children in the group, perhaps unsuspected lesions would have been discovered. Ischemic changes and/or cerebral atrophy, previously recognized in HLHS patients,6 were noted in 4 children in this series, 3 of whom were among the lowest functioning patients. These neuroimaging findings may be acquired either preoperatively or after any of the operations and seem to be a poor prognostic factor in terms of neurodevelopment.
Multiple reports have shown that children with congenital heart disease have a below normal IQ, particularly in the presence of chronic cyanosis.12–14 Patients with HLHS remain cyanotic to varying degrees until the final surgical stage at ∼2 years of age. The possible role that this plays in ultimate intellectual performance cannot be quantified.
Factors related to the surgical procedure performed in early infancy may also have contributed to the findings. Open heart surgery has been shown to have deleterious neurologic effects in a small percentage of infants, both clinically and on a cellular level.17–20These effects may be attributable to CPB and/or deep hypothermic CA. In our study, CPB time did not correlate with intelligence or adaptive behavior, suggesting its impact on overall daily function is not substantial. However, CA time did correlate with intellectual outcome. This is not surprising, because CA has been previously considered as a possible contributor to adverse intellectual outcomes in children with other types of congenital heart disease. The specific effects of CA on intellectual development have been the subject of debate.21–27 Safe periods of CA are reported to be anywhere from 30 to 60 minutes.22–24 The mean CA time in our patients was 56 minutes. The complexity of the stage I Norwood operation, however, does not allow for a short CA time. The correlation that we found between CA time and IQ was primarily in performance of nonverbal tests. The language measures tested in our patients did not correlate with CA time. The reason for this is unclear. Perhaps it is a reflection of the central nervous system's plasticity. That is, although damage sustained by the brain with a prolonged CA time is not likely localized to a specific cerebral hemisphere, certain skills, such as language, may be spared.
In summary, our findings provide evidence that although the staged Norwood procedure can be performed without subsequent severe intellectual or adaptive behavioral impairment, patients perform generally lower than controls. Development of techniques to shorten CA time may further improve the intellectual outcome of infants with HLHS. Longer follow-up and accumulation of additional patients will further contribute to our knowledge of the long-term outlook for children with HLHS.
- Received February 3, 1998.
- Accepted April 23, 1998.
Reprint requests to (J.H.K.) Division of Pediatric Cardiology, New York Hospital–Cornell Medical Center, 525 E 68th St, New York, NY 10021.
- ↵Mosca RS, Bove EL, Crowley DC, Sandhu SS, Schork MA, Kulik TJ. Hemodynamic characteristics of neonates following first stage palliation for hypoplastic left heart syndrome. Circulation. 1995;92:II-267–II-271
- Glauser TA,
- Rorke LB,
- Weinberg PM,
- Clancy RR
- Glauser TA,
- Rorke LB,
- Weinberg PM,
- Clancy RR
- ↵Lezak M. Neuropsychiatry and Assessment. 3rd ed. London, England: Oxford University Press; 1995
- O'Kelly SW,
- Bove EL
- Natowicz M,
- Chatten J,
- Clancy R,
- et al.
- Bellinger DC,
- Wernovsky G,
- Rappaport LA,
- et al.
- Dickinson DF,
- Sambrooks JE
- Copyright © 1998 American Academy of Pediatrics