Subtle hemorrhagic brain injury is associated with neurodevelopmental impairment in infants with repaired congenital heart disease.

OBJECTIVE: Perioperative stroke and periventricular leukomalacia have been reported to occur commonly in infants with congenital heart disease. We aimed to determine the incidence and type of brain injury in infants undergoing 2-ventricle repair in infancy and to determine risk factors associated with such injury. METHODS: Forty-eight infants enrolled in a trial comparing 2 different hematocrits during surgical repair of congenital heart disease underwent brain magnetic resonance imaging scans and neurodevelopmental testing at 1 year of age. RESULTS: Eighteen (38%) of our subjects had tiny foci of hemosiderin by susceptibility imaging, without evidence of abnormalities in corresponding regions on conventional magnetic resonance imaging sequences. Subjects with foci of hemosiderin had a significantly lower Psychomotor Developmental Index at 1 year of age (79.6 +/- 16.5, mean +/- standard deviation) compared with subjects without these foci (89.5 +/- 15.3; P = .04). Older age at surgery and diagnostic group were significantly associated with the presence of hemosiderin foci. Only 1 subject had a small stroke (2%), and 2 subjects had periventricular leukomalacia (4%). CONCLUSION: Foci of hemosiderin without radiologic evidence of ischemic brain injury are an abnormality associated with adverse neurodevelopmental outcome not previously described in magnetic resonance imaging studies of children with surgically repaired congenital heart disease. The association of hemosiderin foci with older age at surgery and cardiac diagnosis, and not with risk factors associated with brain injury, in previous studies suggests that the cause and pathogenesis of this abnormality are different from ischemic brain lesions reported previously.

Randomized trial of hematocrit 25% versus 35% during hypothermic cardiopulmonary bypass in infant heart surgery.

OBJECTIVES: We previously reported that postoperative hemodynamics and developmental outcomes were better among infants randomized to a higher hematocrit value during hypothermic cardiopulmonary bypass. However, worse outcomes were concentrated in patients with hematocrit values of 20% or below, and the benefits of hematocrit values higher than 25% were uncertain. METHODS: We compared perioperative hemodynamics and, at 1 year, developmental outcome and brain magnetic resonance imaging in a single-center, randomized trial of hemodilution to a hematocrit value of 25% versus 35% during hypothermic radiopulmonary bypass for reparative heart surgery in infants undergoing 2-ventricle repairs without aortic arch obstruction. RESULTS: Among 124 subjects, 56 were assigned to the lower-hematocrit strategy (24.8% +/- 3.1%, mean +/- SD) and 68 to the higher-hematocrit strategy (32.6% +/- 3.5%). Infants randomized to the 25% strategy, compared with the 35% strategy, had a more positive intraoperative fluid balance (P = .007) and lower regional cerebral oxygen saturation at 10 minutes after cooling (P = .04) and onset of low flow (P = .03). Infants with dextro-transposition of the great arteries in the 25% group had significantly longer hospital stay. Other postoperative outcomes, blood product usage, and adverse events were similar in the treatment groups. At age 1 year (n = 106), the treatment groups had similar scores on the Psychomotor and Mental Development Indexes of the Bayley Scales; both groups scored significantly worse than population norms. CONCLUSIONS: Hemodilution to hematocrit levels of 35% compared with those of 25% had no major benefits or risks overall among infants undergoing 2-ventricle repair. Developmental outcomes at age 1 year in both randomized groups were below those in the normative population.

Regional low-flow perfusion versus circulatory arrest in neonates: one-year neurodevelopmental outcome.

BACKGROUND: Regional low-flow perfusion of the brain is a bypass technique commonly used during stage 1 reconstruction in neonates with hypoplastic left heart syndrome and related variants. The neurodevelopmental outcome of these children is unknown. METHODS: Twenty-nine infants (22 boys, 7 girls) with hypoplastic left heart syndrome or variant requiring single ventricle palliation and aortic arch reconstruction were studied between 1999 and 2004. Mental Developmental Index (MDI) and Psychomotor Developmental Index were assessed using Bayley Scales of Infant Development and correlated with intraoperative and perioperative variables. Results are reported as mean +/- standard deviation. RESULTS: Average age at stage 1 operation and at bidirectional Glenn was 7 +/- 8 days and 6.0 +/- 2 months, respectively. The MDI was in the low average range (87.7 +/- 13.2). The Psychomotor Developmental Index was in the mildly delayed range (75.2 +/- 14.5). Regional low-flow perfusion was used in 31% (9 of 29 patients), with an average circulatory arrest time of 23.5 +/- 13.4 minutes. Deep hypothermia and circulatory arrest was used as the primary operative strategy in 69% of patients (20 of 29 patients), with an average circulatory arrest time of 44.3 +/- 15.3 minutes (p = 0.003). No differences in MDI or Psychomotor Developmental Index scores were observed between the regional low-flow perfusion and non-regional low-flow perfusion groups (MDI, 88.0 +/- 12.1 versus 87.6 +/- 14.0; p = 0.93, respectively; Psychomotor Developmental Index, 75.5 +/- 15.1 versus 75.0 +/- 14.6; p = 0.93, respectively). Lowest operative temperature (<16 degrees C) and birth order (<2 versus >3) significantly related to MDI (89.6 versus 72.8; p = 0.047). CONCLUSIONS: At 1 year of age, neurodevelopmental outcomes of patients undergoing stage 1 using regional low-flow perfusion were similar to outcomes observed in children exposed to circulatory arrest. The association of birth order and MDI suggests that early intervention may benefit these patients.

Relationship of surgical approach to neurodevelopmental outcomes in hypoplastic left heart syndrome.

OBJECTIVE: Two strategies for surgical management are used for infants with hypoplastic left heart syndrome (HLHS), primary heart transplantation and the Norwood procedure. We sought to determine how these 2 surgical approaches influence neurodevelopmental outcomes at school age. METHODS: A multicenter, cross-sectional study of neurodevelopmental outcomes among school-aged children (>8 years of age) with HLHS was undertaken between July 2003 and September 2004. Four centers enrolled 48 subjects, of whom 47 completed neuropsychologic testing. Twenty-six subjects (55%) had undergone the Norwood procedure and 21 (45%) had undergone transplantation, with an intention-to-treat analysis. The mean age at testing was 12.4 +/- 2.5 years. Evaluations included the Wechsler Abbreviated Scale of Intelligence, Clinical Evaluation of Language Fundamentals, Wechsler Individual Achievement Test, and Beery-Buktenica Developmental Test of Visual-Motor Integration. RESULTS: The mean neurocognitive test results were significantly below population normative values. The mean full-scale IQ for the entire cohort was 86 +/- 14. In a multivariate model, there was no association of surgical strategy with any measure of developmental outcome. A longer hospital stay, however, was associated significantly with lower verbal, performance, and full-scale IQ scores. Aortic valve atresia was associated with lower math achievement test scores. CONCLUSIONS: Neurodevelopmental deficits are prevalent among school-aged children with HLHS, regardless of surgical approach. Complications that result in prolonged hospitalization at the time of the initial operation are associated with neurodevelopmental status at school age.

The influence of hemodilution on outcome after hypothermic cardiopulmonary bypass: results of a randomized trial in infants.

BACKGROUND: We hypothesized that cognitive impairment and hemodynamic instability after infant cardiac surgery with cardiopulmonary bypass might be exacerbated by hemodilution. METHODS: In a single-center randomized trial with blinded assessment of outcomes, we compared use of 2 hemodilution protocols during hypothermic cardiopulmonary bypass with infant cardiac surgery. The primary perioperative end point was lowest cardiac index in the first 24 hours postoperatively, and primary end points at age 1 year were scores on the Psychomotor Development Index and Mental Developmental Index of the Bayley Scales. RESULTS: Among 147 subjects, 74 were assigned to the lower-hematocrit strategy (21.5% +/- 2.9%, mean +/- SD at onset of low-flow bypass) and 73 to the higher-hematocrit strategy (27.8% +/- 3.2%). In intent-to-treat analyses the lower-hematocrit group had lower nadirs of cardiac index (P =.02), higher serum lactate levels 60 minutes after cardiopulmonary bypass (P =.03), and a greater percentage increase in total body water on the first postoperative day (P =.006). Blood product use and adverse events were similar in the 2 groups. At age 1 year (113 children), the lower-hematocrit group had worse scores on the Psychomotor Development Index (81.9 +/- 15.7 vs 89.7 +/- 14.7, P =.008), as well as more Psychomotor Development Index scores at least 2 SDs below the population mean (16/56 [29%] vs 5/53 [9%], P =.01). The groups had similar Mental Developmental Index scores and findings on neurologic examination. Inferences using hematocrit as a continuous variable were similar to those based on intent-to-treat analyses. CONCLUSIONS: Hemodilution to a hematocrit level in wide use for cardiopulmonary bypass and thought to be safe is associated with adverse perioperative and developmental outcomes in infants.

Influence of parental stress and social support on the behavioral adjustment of children with transposition of the great arteries.

The joint role of parent stress and social support in the emotional adjustment of children was examined prospectively in a group of children with d-transposition of the great arteries (d-TGA). Questionnaires on parent perceptions of stress and social support were administered when children were 1 and 4 years of age (n = 143-153). Parent ratings of child behavior problems were collected at 4 years (n = 152). The findings indicate a favorable outcome for parents and children with congenital heart disease (CHD). Compared with normative samples, parents experienced less stress and more social support, and they rated children as showing fewer behavior problems. Parents with more stress at both ages reported more behavior problems. Families with less social support reported more stress at both 1 and 4 years. Social support, however, did not moderate the relationship between stress and child behavior problems. Early detection of distressed families may assist in alleviating stress and reducing behavior problems.

Neurodevelopmental outcome after congenital heart surgery: results from an institutional registry.

OBJECTIVE: Increased survival in children with critical congenital heart disease (CHD) has raised interest in the neurodevelopmental sequelae of these lesions. This investigation is part of an institutional effort to examine the neurodevelopment of 5-year-old children following repair or palliation of CHD. METHODS: We performed a battery of neuropsychological tests on a sample of 243 children between 1998 and 2001. RESULTS: In the sample as a whole, mean full-scale (FSIQ), verbal (VIQ), and performance (PIQ) IQ scores were in the normal range (96.8+/-15.9, 97.8+/-14.6, and 96.3+/-17.1, respectively). Anatomic, demographic, and perioperative factors were assessed for impact on neurodevelopment. In multiple regression analysis, lower socioeconomic status (SES) and the diagnosis of velocardiofacial syndrome (VCFS) predicted a lower FSIQ (P=0.01, and P=0.001, respectively). A single ventricle diagnosis (P=0.06), longer postoperative ICU stay (P=0.08), and cumulative duration of hypothermic circulatory arrest (HCA) (P=0.09) approached significance as predictors of lower FSIQ. CONCLUSION: Children with CHD, on the whole, appear to be performing within the average range in terms of intellectual abilities. Lower SES and VCFS are associated with lower IQ scores. Trends toward worse outcomes were observed in single ventricle patients, biventricular patients with longer postrepair ICU stays, and patients subjected to longer periods of HCA.

Neurodevelopmental outcomes after biventricular repair of congenital heart defects.

OBJECTIVE: This study was undertaken to assess neurodevelopment of children after biventricular repair of congenital heart defects. METHODS: Full-scale, performance, and verbal IQs of 69 patients who had undergone biventricular repair were assessed at 5 years of age with the Wechsler Preschool and Primary Scales of Intelligence-Revised. The Wide Range Assessment of Visual-Motor Abilities was used to measure visual-motor skills. Regression analyses adjusting for parental IQ and socioeconomic status were used to evaluate outcome predictors. RESULTS: Median age at repair was 91 days (range 1-1558 days). Hypothermic circulatory arrest was used in 35 cases (mean duration of hypothermic circulatory arrest 33 +/- 17 minutes). Mean full-scale, performance, and verbal IQs for the entire study population were within the reference range (full-scale 96.9 +/- 15.9, performance 96.6 +/- 16.8, verbal 97.7 +/- 15.2). Anatomic diagnosis, age at operation, and use of hypothermic circulatory arrest did not influence full-scale IQ (P =.66, P =.14, and P =.46, respectively), performance IQ (P =.64, P =.36, and P =.73, respectively), or verbal IQ (P =.74, P =.08, and P =.39, respectively). Among patients subjected to hypothermic circulatory arrest, duration of arrest was evaluated as a predictor of outcome. After adjustment for parental IQ, full-scale (P =.12), performance (P =.07), and verbal (P =.22) IQ scores of patients with more than 39 minutes of hypothermic circulatory arrest were not different from those of patients who had arrest periods of 39 minutes or less. After adjustment for socioeconomic status, however, full-scale (P =.05) and performance (P =.03) IQ scores were lower among patients who had more than 39 minutes of hypothermic circulatory arrest. After adjustment for either parental IQ or socioeconomic status, patients with more than 39 minutes of arrest had lower scores on Wide Range Assessment of Visual-Motor Abilities subtests of visual-motor and fine motor abilities and on several performance IQ subtests. CONCLUSIONS: IQs of patients who had undergone biventricular repair of congenital heart defects were within the reference range. However, hypothermic circulatory arrest for longer than 39 minutes was associated with deficits in visual-motor and fine motor skills and possibly in full-scale IQ.