Transplantation-free survival and interventions at 3 years in the single ventricle reconstruction trial.

BACKGROUND: In the Single Ventricle Reconstruction (SVR) trial, 1-year transplantation-free survival was better for the Norwood procedure with right ventricle-to-pulmonary artery shunt (RVPAS) compared with a modified Blalock-Taussig shunt (MBTS). At 3 years, we compared transplantation-free survival, echocardiographic right ventricular ejection fraction, and unplanned interventions in the treatment groups. METHODS AND RESULTS: Vital status and medical history were ascertained from annual medical records, death indexes, and phone interviews. The cohort included 549 patients randomized and treated in the SVR trial. Transplantation-free survival for the RVPAS versus MBTS groups did not differ at 3 years (67% versus 61%; P=0.15) or with all available follow-up of 4.8±1.1 years (log-rank P=0.14). Pre-Fontan right ventricular ejection fraction was lower in the RVPAS group than in the MBTS group (41.7±5.1% versus 44.7±6.0%; P=0.007), and right ventricular ejection fraction deteriorated in RVPAS (P=0.004) but not MBTS (P=0.40) subjects (pre-Fontan minus 14-month mean, -3.25±8.24% versus 0.99±8.80%; P=0.009). The RVPAS versus MBTS treatment effect had nonproportional hazards (P=0.004); the hazard ratio favored the RVPAS before 5 months (hazard ratio=0.63; 95% confidence interval, 0.45-0.88) but the MBTS beyond 1 year (hazard ratio=2.22; 95% confidence interval, 1.07-4.62). By 3 years, RVPAS subjects had a higher incidence of catheter interventions (P<0.001) with an increasing HR over time (P=0.005): <5 months, 1.14 (95% confidence interval, 0.81-1.60); from 5 months to 1 year, 1.94 (95% confidence interval, 1.02-3.69); and >1 year, 2.48 (95% confidence interval, 1.28-4.80). CONCLUSIONS: By 3 years, the Norwood procedure with RVPAS compared with MBTS was no longer associated with superior transplantation-free survival. Moreover, RVPAS subjects had slightly worse right ventricular ejection fraction and underwent more catheter interventions with increasing hazard ratio over time. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00115934.

The relationship of patient medical and laboratory characteristics to changes in functional health status in children and adolescents after the Fontan procedure.

Despite hypothesized concerns about deterioration beginning in adolescence, longitudinal data and associated factors regarding standardized assessment of physical functioning are not available for Fontan patients. Parents who participated in the Fontan Cross-Sectional Study completed the Child Health Questionnaire at 2 time points for 245 subjects ages 6-18 years. Associations between change in Physical Functioning Summary Score and baseline patient, medical, and laboratory characteristics (mean age 9.5 ± 1.7 years) and follow-up patient and medical characteristics (mean age 16.2 ± 1.6 years) were determined by regression analyses. During a mean of 6.7 ± 0.4 years, a small (not clinically important) but statistically significant decrease in score from 46.2 ± 11.7 to 44.5 ± 12.1 (p < 0.03) was noted. Subjects with higher baseline scores had a greater decrease in score (r = -0.48; p < 0.001). A multivariable model of patient and medical characteristics (R(2) = 0.11) showed that a greater decrease in score was significantly associated with interim development of asthma (n = 13; parameter estimate [PE] -6.6; p < 0.05) or other chronic respiratory, lung, or breathing problems (n = 13; PE -12.5; p < 0.001) and the presence of protein-losing enteropathy at any time (n = 12; PE -9.4; p = 0.006). Change in score was not significantly associated with baseline laboratory measures of exercise capacity and ventricular characteristics and function. Therefore, although physical functioning may be stable during adolescence for many Fontan patients, deterioration occurs in some in association with respiratory conditions and protein-losing enteropathy. Further longitudinal study is necessary to better understand the relationship between clinical morbidities and functional health status as these patients transition into adulthood.

Association of impaired linear growth and worse neurodevelopmental outcome in infants with single ventricle physiology: a report from the pediatric heart network infant single ventricle trial.

OBJECTIVES: To describe neurodevelopmental outcomes in infants with single ventricle (SV) physiology and determine factors associated with worse outcomes. STUDY DESIGN: Neurodevelopmental outcomes for infants with SV enrolled in a multicenter drug trial were assessed at 14 months of age using the Bayley Scales of Infant Development-II. Multivariable regression analysis was used to identify factors associated with worse outcomes. RESULTS: Neurodevelopmental testing was performed at 14 ± 1 months in 170/185 subjects in the trial. Hypoplastic left heart syndrome was present in 59% and 75% had undergone the Norwood operation. Mean Psychomotor Developmental Index (PDI) and mental developmental index (MDI) were 80 ± 18 and 96 ± 14, respectively, (normal 100 ± 15, P < .001 for each). Group-based trajectory analysis provided a 2-group model ("high" and "low") for height z-score trajectory and brain type natriuretic peptide (BNP) trajectory. The predicted PDI scores were 15 points higher in the "high" height z-score trajectory compared with the "low" cluster (P < .001). A higher number of serious adverse events during the trial was associated with lower PDI scores (P = .02). The predicted MDI scores were 13-17 points lower in "low height trajectory-high BNP trajectory" group compared with the other 3 groups (P < .001). MDI scores were also lower in subjects who required extracorporeal membrane oxygenation during the neonatal hospitalization (P = .01) or supplemental oxygen at discharge (P = .01). CONCLUSIONS: Neurodevelopmental outcome at 14 months of age is impaired in infants with SV physiology. Low height trajectory and high BNP trajectory were associated with worse neurodevelopmental outcomes. Efforts to improve nutritional status alone may not improve neurodevelopmental outcomes.

Evaluation of the utility of radiography in acute bronchiolitis.

OBJECTIVES: To determine the proportion of radiographs inconsistent with bronchiolitis in children with typical presentation of bronchiolitis and to compare rates of intended antibiotic therapy before radiography versus those given antibiotics after radiography. STUDY DESIGN: We conducted a prospective cohort study in a pediatric emergency department of 265 infants aged 2 to 23 months with radiographs showing either airway disease only (simple bronchiolitis), airway and airspace disease (complex bronchiolitis), and inconsistent diagnoses (eg, lobar consolidation). RESULTS: The rate of inconsistent radiographs was 2 of 265 cases (0.75%; 95% CI 0-1.8). A total of 246 children (92.8%) had simple radiographs, and 17 radiographs (6.9%) were complex. To identify 1 inconsistent and 1 complex radiograph requires imaging 133 and 15 children, respectively. Of 148 infants with oxygen saturation >92% and a respiratory disease assessment score <10 of 17 points, 143 (96.6%) had a simple radiograph, compared with 102 of 117 infants (87.2%) with higher scores or lower saturation (odds ratio, 3.9; 95% CI, 1.3-14.3). Seven infants (2.6%) were identified for antibiotics pre-radiography; 39 infants (14.7%) received antibiotics post-radiography (95% CI, 8-16). CONCLUSIONS: Infants with typical bronchiolitis do not need imaging because it is almost always consistent with bronchiolitis. Risk of airspace disease appears particularly low in children with saturation higher than 92% and mild to moderate distress.

Remote ischemic preconditioning in children undergoing cardiac surgery with cardiopulmonary bypass: a single-center double-blinded randomized trial.

BACKGROUND: Remote ischemic preconditioning (RIPC) harnesses an innate defensive mechanism that protects against inflammatory activation and ischemia-reperfusion injury, known sequelae of cardiac surgery with cardiopulmonary bypass. We sought to determine the impact of RIPC on clinical outcomes and physiological markers related to ischemia-reperfusion injury and inflammatory activation after cardiac surgery in children. METHODS AND RESULTS: Overall, 299 children (aged neonate to 17 years) were randomized to receive an RIPC stimulus (inflation of a blood pressure cuff on the left thigh to 15 mm Hg above systolic for four 5-minute intervals) versus a blinded sham stimulus during induction with a standardized anesthesia protocol. Primary outcome was duration of postoperative hospital stay, with serial clinical and laboratory measurements for the first 48 postoperative hours and clinical follow-up to discharge. There were no significant baseline differences between RIPC (n=148) and sham (n=151). There were no in-hospital deaths. No significant difference in length of postoperative hospital stay was noted (sham 5.4 versus RIPC 5.6 days; difference +0.2; adjusted P=0.91), with the 95% confidence interval (-0.7 to +0.9) excluding a prespecified minimal clinically significant differences of 1 or 1.5 days. There were few significant differences in other clinical outcomes or values at time points or trends in physiological markers. Benefit was not observed in specific subgroups when explored through interactions with categories of age, sex, surgery type, Aristotle score, or first versus second half of recruitment. Adverse events were similar (sham 5%, RIPC 6%; P=0.68). CONCLUSIONS: RIPC is not associated with important improvements in clinical outcomes and physiological markers after cardiac surgery in children. CLINICAL TRIAL REGISTRATION URL: clinicaltrials.gov. Unique identifier: NCT00650507.

Longitudinal assessment of growth in hypoplastic left heart syndrome: results from the single ventricle reconstruction trial.

BACKGROUND: We sought to characterize growth between birth and age 3 years in infants with hypoplastic left heart syndrome who underwent the Norwood procedure. METHODS AND RESULTS: We performed a secondary analysis using the Single Ventricle Reconstruction Trial database after excluding patients <37 weeks gestation (N=498). We determined length-for-age z score (LAZ) and weight-for-age z score (WAZ) at birth and age 3 years and change in WAZ over 4 clinically relevant time periods. We identified correlates of change in WAZ and LAZ using multivariable linear regression with bootstrapping. Mean WAZ and LAZ were below average relative to the general population at birth (P<0.001, P=0.05, respectively) and age 3 years (P<0.001 each). The largest decrease in WAZ occurred between birth and Norwood discharge; the greatest gain occurred between stage II and 14 months. At age 3 years, WAZ and LAZ were <-2 in 6% and 18%, respectively. Factors associated with change in WAZ differed among time periods. Shunt type was associated with change in WAZ only in the Norwood discharge to stage II period; subjects with a Blalock-Taussig shunt had a greater decline in WAZ than those with a right ventricle-pulmonary artery shunt (P=0.002). CONCLUSIONS: WAZ changed over time and the predictors of change in WAZ varied among time periods. By age 3 years, subjects remained small and three times as many children were short as were underweight (>2 SD below normal). Failure to find consistent risk factors supports the strategy of tailoring nutritional therapies to patient- and stage-specific targets. CLINICAL TRIAL REGISTRATION URL: http://clinicaltrials.gov/. Unique identifier: NCT00115934.

Prenatal diagnosis and risk factors for preoperative death in neonates with single right ventricle and systemic outflow obstruction: screening data from the Pediatric Heart Network Single Ventricle Reconstruction Trial(∗).

OBJECTIVES: The purpose of this analysis was to assess preoperative risk factors before the first-stage Norwood procedure in infants with hypoplastic left heart syndrome and related single-ventricle lesions and to evaluate practice patterns in prenatal diagnosis, as well as the role of prenatal diagnosis in outcome. METHODS: Data from all live births with morphologic single right ventricle and systemic outflow obstruction screened for the Pediatric Heart Network's Single Ventricle Reconstruction Trial were used to investigate prenatal diagnosis and preoperative risk factors. Demographics, gestational age, prenatal diagnosis status, presence of major extracardiac congenital abnormalities, and preoperative mortality rates were recorded. RESULTS: Of 906 infants, 677 (75%) had prenatal diagnosis, 15% were preterm (<37 weeks' gestation), and 16% were low birth weight (<2500 g). Rates of prenatal diagnosis varied by study site (59% to 85%, P < .0001). Major extracardiac congenital abnormalities were less prevalent in those born after prenatal diagnosis (6% vs 10%, P = .03). There were 26 (3%) deaths before Norwood palliation; preoperative mortality did not differ by prenatal diagnosis status (P = .49). In multiple logistic regression models, preterm birth (P = .02), major extracardiac congenital abnormalities (P < .0001), and obstructed pulmonary venous return (P = .02) were independently associated with preoperative mortality. CONCLUSIONS: Prenatal diagnosis occurred in 75%. Preoperative death was independently associated with preterm birth, obstructed pulmonary venous return, and major extracardiac congenital abnormalities. Adjusted for gestational age and the presence of obstructed pulmonary venous return, the estimated odds of preoperative mortality were 10 times greater for subjects with a major extracardiac congenital abnormality.

A single versus multiple doses of dexamethasone in infants wheezing for the first time.

RATIONALE: Corticosteroid therapy is not routinely recommended in true bronchiolitis. However, since bronchiolitis and the first asthma attack are impossible to distinguish, some infants with the first wheezing episode receive corticosteroids. Optimal duration of corticosteroid therapy in this scenario is unknown. This study compared efficacy of multiple administrations and a single dose of dexamethasone in bronchiolitis. METHODS: In this randomized double blind trial, previously healthy outpatients 2-23 months of age with bronchiolitis and Respiratory Disease Assessment Instrument (RDAI) score 6 or more received 1 mg/kg of oral dexamethasone in the Emergency Department. Prior to discharge at 4 hr they were randomized to either 4 daily doses of dexamethasone 0.15 mg/kg or placebo equivalent. Primary outcome was the proportion of subsequent hospitalizations or prescribed trials of bronchodilator/corticosteroid therapy for dyspnea by day 6 in the groups. Secondary outcomes were changes in the RDAI to day 6, and proportions with unscheduled visits by days 6 and 28. RESULTS: The rate of primary outcome in the single dose group (SDG, N = 64) was 9/64 or 14.1% versus 7/61 or 11.5% in the multiple dose group (MDG, N = 61) [95% CI 0.09; 0.14]. Twelve (18.8%) children in the SDG had unscheduled medical visits by day 6 versus 11 (18.0%) children in the MDG [95% CI 0.13; 0.14]. On day 6 the RDAI decreased from 9.5 +/- 2.1 to 2.1 +/- 2.4 in the SDG and from 9.8 +/- 2.2 to 1.6 +/- 2.3 in the MDG [95% CI 0.36; 2.06]. Between days 7-28, 24/64 (37.5%) SDG infants returned for care versus 20/61 (32.8%) of the MDG [95% CI 0.12; 0.21]. CONCLUSIONS: Our study suggests that, in outpatients with bronchiolitis who receive dexamethasone, continuation of this agent beyond the initial dose does not provide significant benefit.

High-dose inhaled fluticasone does not replace oral prednisolone in children with mild to moderate acute asthma.

BACKGROUND: Inhaled corticosteroids are not as effective as oral corticosteroids in school-aged children with severe acute asthma. It is uncertain how inhaled corticosteroids compare with oral corticosteroids in mild to moderate exacerbations. PRIMARY OBJECTIVE: The purpose of this work was to determine whether there is a significant difference in the percentage of predicted forced expiratory volume in 1 second in children with mild to moderate acute asthma treated with either inhaled fluticasone or oral prednisolone. METHODS: This was a randomized, double-blind controlled trial conducted between 2001 and 2004 in a tertiary care pediatric emergency department. We studied a convenience sample of 69 previously healthy children 5 to 17 years of age with acute asthma and forced expiratory volume in 1 second at 50% to 79% predicted value; 41 families refused participation. Albuterol was given in the emergency department and salmeterol was given after discharge to all patients, as well as either 2 mg of fluticasone via metered dose inhaler and valved holding chamber in the emergency department plus 500 microg twice daily via Diskus for 10 doses after discharge (fluticasone group, N = 35) or 2 mg/kg of oral prednisolone in the emergency department plus 5 daily doses of 1 mg/kg of prednisolone after discharge (prednisolone group, N = 34). We measured a priori defined absolute change in percent predicted forced expiratory volume in 1 second from baseline to 4 and 48 hours in the 2 groups. RESULTS. At 240 minutes, the forced expiratory volume in 1 second increased by 19.1% +/- 12.7% in the fluticasone group and 29.8% +/- 15.5% in the prednisolone group. At 48 hours, this difference was no longer significant (estimated difference: 4.0 +/- 3.4; P = .14). The relapse rates by 48 hours were 12.5% and 0% in the fluticasone group and prednisolone group, respectively. CONCLUSION: Airway obstruction in children with mild to moderate acute asthma in the emergency department improves faster on oral than inhaled corticosteroids.