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Newburger, Jane

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Newburger

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Jane

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Newburger, Jane
Author's Publications: search.filters.isAuthorOfPublication.c1f4e082-3974-4d55-8d59-3c6da14441aa

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Now showing 1 - 10 of 15
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    Graph theory analysis of cortical thickness networks in adolescents with d‐transposition of the great arteries
    (John Wiley and Sons Inc., 2018) Watson, Christopher G.; Stopp, Christian; Newburger, Jane; Rivkin, Michael
    Abstract Objective: Adolescents with d‐transposition of the great arteries (d‐TGA) who had the arterial switch operation in infancy have been found to have structural brain differences compared to healthy controls. We used cortical thickness measurements obtained from structural brain MRI to determine group differences in global brain organization using a graph theoretical approach. Methods: Ninety‐two d‐TGA subjects and 49 controls were scanned using one of two identical 1.5‐Tesla MRI systems. Mean cortical thickness was obtained from 34 regions per hemisphere using Freesurfer. A linear model was used for each brain region to adjust for subject age, sex, and scanning location. Structural connectivity for each group was inferred based on the presence of high inter‐regional correlations of the linear model residuals, and binary connectivity matrices were created by thresholding over a range of correlation values for each group. Graph theory analysis was performed using packages in R. Permutation tests were performed to determine significance of between‐group differences in global network measures. Results: Within‐group connectivity patterns were qualitatively different between groups. At lower network densities, controls had significantly more long‐range connections. The location and number of hub regions differed between groups: controls had a greater number of hubs at most network densities. The control network had a significant rightward asymmetry compared to the d‐TGA group at all network densities. Conclusions: Using graph theory analysis of cortical thickness correlations, we found differences in brain structural network organization among d‐TGA adolescents compared to controls. These may be related to the white matter and gray matter differences previously found in this cohort, and in turn may be related to the cognitive deficits this cohort presents.
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    Neighborhood Socioeconomic Status and Outcomes Following the Norwood Procedure: An Analysis of the Pediatric Heart Network Single Ventricle Reconstruction Trial Public Data Set
    (John Wiley and Sons Inc., 2018) Bucholz, Emily; Sleeper, Lynn; Newburger, Jane
    Background: Children with single ventricle heart disease require frequent interventions and follow‐up. Low socioeconomic status (SES) may limit access to high‐quality care and place these children at risk for poor long‐term outcomes. Methods and Results: Data from the SVR (Pediatric Heart Network Single Ventricle Reconstruction Trial Public Use) data set were used to examine the relationship of US neighborhood SES with 30‐day and 1‐year mortality or cardiac transplantation and length of stay among neonates undergoing the Norwood procedure (n=525). Crude rates of death or transplantation at 1 year after Norwood were highest for patients living in neighborhoods with low SES (lowest tertile 37.0% versus middle tertile 31.0% versus highest tertile 23.6%, P=0.024). After adjustment for patient demographics, birth characteristics, and anatomy, patients in the highest SES tertile had significantly lower risk of death or transplant than patients in the lowest SES tertile (hazard ratio 0.62, 95% confidence interval, 0.40, 0.96). When SES was examined continuously, the hazard of 1‐year death or transplant decreased steadily with increasing neighborhood SES. Hazard ratios for 30‐day transplant‐free survival and 1‐year transplant‐free survival were similar in magnitude. There were no significant differences in length of stay following the Norwood procedure by SES. Conclusions: Low neighborhood SES is associated with worse 1‐year transplant‐free survival after the Norwood procedure, suggesting that socioeconomic and environmental factors may be important determinants of outcome in critical congenital heart disease. Future studies should investigate aspects of SES and environment amenable to intervention. Clinical Trial Registration URL:http://www.clinicaltrials.gov> http://www.clinicaltrials.gov. Unique identifier: NCT00115934.
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    The impact of socio-economic status on health related quality of life for children and adolescents with heart disease
    (BioMed Central, 2013) Cassedy, Amy; Drotar, Dennis; Ittenbach, Richard; Hottinger, Shawna; Wray, Jo; Wernovsky, Gil; Newburger, Jane; Mahony, Lynn; Mussatto, Kathleen; Cohen, Mitchell I; Marino, Bradley S
    Background: Socioeconomic status (SES) is known to influence children’s health-related quality of life. Many SES indicators assess distinct dimensions of a family’s position rather than measuring the same underlying construct. Many researchers, however, see SES indicators as interchangeable. The primary aim of this study was to determine which measure of SES had the strongest impact on health-related quality of life. Methods: This is a secondary analysis of the Pediatric Cardiac Quality of Life Inventory Validation Study. The SES variables were family income, Hollingshead Index (occupational prestige), and highest parent educational attainment level. Health-related quality of life was measured using the Pediatric Cardiac Quality of Life Inventory. Correlations tested the relationship among the three SES indicators. Regression-based modeling was used to calculate the strength of the association between SES measures and the Pediatric Cardiac Quality of Life Inventory. Results: The correlations among the SES measures were moderately high, with the correlation between the Hollingshead Index and parental education being r = 0.62 (95% CI = 0.56-0.65). There were equally high correlations between family income and the Hollingshead (r = 0.61, 95% CI = 0.57-0.65) and a slightly lower correlation between family income and parental education (r = 0.55, 95% CI = 0.52-0.59). Family income had the highest explanatory value compared to the Hollingshead Index or parental educational attainment, while controlling for sex, race, current cardiac status, and original diagnosis, accounting for 4-5% of the variation in patient and parent Pediatric Cardiac Quality of Life Inventory Total score, respectively, compared to the other SES measures. Conclusion: Family income as an SES measure demonstrated the greatest fidelity with respect to health-related quality of life as measured by the Pediatric Cardiac Quality of Life Inventory across respondent groups and explained more of the variation compared to the Hollingshead Index or highest parental educational attainment.
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    Longitudinal Assessment of Growth in Hypoplastic Left Heart Syndrome: Results From the Single Ventricle Reconstruction Trial
    (Blackwell Publishing Ltd, 2014) Burch, Phillip T.; Gerstenberger, Eric; Ravishankar, Chitra; Hehir, David A.; Davies, Ryan R.; Colan, Steven; Sleeper, Lynn A.; Newburger, Jane; Clabby, Martha L.; Williams, Ismee A.; Li, Jennifer S.; Uzark, Karen; Cooper, David S.; Lambert, Linda M.; Pemberton, Victoria L.; Pike, Nancy A.; Anderson, Jeffrey B.; Dunbar‐Masterson, Carolyn; Khaikin, Svetlana; Zyblewski, Sinai C.; Minich, L. LuAnn
    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.
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    Temporal Trends in Pulse Pressure and Mean Arterial Pressure During the Rise of Pediatric Obesity in US Children
    (Blackwell Publishing Ltd, 2014) Zachariah, Justin P.; Graham, Dionne; de Ferranti, Sarah D.; Vasan, Ramachandran S.; Newburger, Jane; Mitchell, Gary F.
    Background: Somatic growth in childhood is accompanied by substantial remodeling of the aorta. Obesity is associated with increased aortic stiffness and flow and may interfere with aortic remodeling during growth. Wide pulse pressure (PP) indicates mismatch between aortic impedance and pulsatile flow and increases risk for future systolic hypertension and cardiovascular disease (CVD). We hypothesized that the rise of pediatric obesity would be associated with a temporal trend to higher PP. Methods and Results: We analyzed demographic, anthropometric, and blood pressure (BP) data for 8‐ to 17‐year‐old children (N=16 457) from the cross‐sectional National Health and Nutrition Examination Surveys (NHANES) for 1976 through 2008. Multivariable adjusted survey regression was used to examine temporal trends in PP and mean arterial pressure (MAP) and the relation to obesity. Across this period, unadjusted PP was higher (0.29 mm Hg/y, 95% CI 0.26 to 0.33 mm Hg/y; P<0.0001), while MAP was lower (−0.24 mm Hg/y, 95% CI −0.27 to −0.20 mm Hg/y; P<0.0001) across examinations. Adjusting for body mass index partially attenuated the temporal trend for PP by 32% (P<0.0001). Obesity amplified the relation between taller height and higher PP (from 0.23 [95% CI 0.19 to 0.28] to 0.27 [95% CI 0.21 to 0.34] mm Hg/cm height in boys and from 0.08 [95% CI 0.04 to 0.13] to 0.22 [95% CI 0.13 to 0.31] mm Hg/cm height in girls; P<0.01 for both). Conclusions: PP has increased during the rise of pediatric obesity. Higher PP may indicate mismatch between aortic diameter, wall stiffness, and flow in obese children during a period of rapid somatic growth when the aorta is already under considerable remodeling stress.
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    Non-invasive Assessment of Cerebral Blood Flow and Oxygen Metabolism in Neonates during Hypothermic Cardiopulmonary Bypass: Feasibility and Clinical Implications
    (Nature Publishing Group, 2017) Ferradal, Silvina L.; Yuki, Koichi; Vyas, Rutvi; Ha, Christopher G.; Yi, Francesca; Stopp, Christian; Wypij, David; Cheng, Henry; Newburger, Jane; Kaza, Aditya; Franceschini, Maria; Kussman, Barry; Grant, P.
    The neonatal brain is extremely vulnerable to injury during periods of hypoxia and/or ischemia. Risk of brain injury is increased during neonatal cardiac surgery, where pre-existing hemodynamic instability and metabolic abnormalities are combined with long periods of low cerebral blood flow and/or circulatory arrest. Our understanding of events associated with cerebral hypoxia-ischemia during cardiopulmonary bypass (CPB) remains limited, largely due to inadequate tools to quantify cerebral oxygen delivery and consumption non-invasively and in real-time. This pilot study aims to evaluate cerebral blood flow (CBF) and oxygen metabolism (CMRO2) intraoperatively in neonates by combining two novel non-invasive optical techniques: frequency-domain near-infrared spectroscopy (FD-NIRS) and diffuse correlation spectroscopy (DCS). CBF and CMRO2 were quantified before, during and after deep hypothermic cardiopulmonary bypass (CPB) in nine neonates. Our results show significantly decreased CBF and CMRO2 during hypothermic CPB. More interestingly, a change of coupling between both variables is observed during deep hypothermic CPB in all subjects. Our results are consistent with previous studies using invasive techniques, supporting the concept of FD-NIRS/DCS as a promising technology to monitor cerebral physiology in neonates providing the potential for individual optimization of surgical management.
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    Coronary Artery Aneurysms in Kawasaki Disease: Risk Factors for Progressive Disease and Adverse Cardiac Events in the US Population
    (John Wiley and Sons Inc., 2016) Friedman, Kevin; Gauvreau, Kimberly; Hamaoka‐Okamoto, Akiko; Tang, Alexander; Berry, Erika; Tremoulet, Adriana H.; Mahavadi, Vidya S.; Baker, Annette; deFerranti, Sarah D.; Fulton, David; Burns, Jane C.; Newburger, Jane
    Background: The natural history of coronary artery aneurysms (CAA) after intravenous immunoglobulin (IVIG) treatment in the United States is not well described. We describe the natural history of CAA in US Kawasaki disease (KD) patients and identify factors associated with major adverse cardiac events (MACE) and CAA regression. Methods and Results: We evaluated all KD patients with CAA at 2 centers from 1979 to 2014. Factors associated with CAA regression, maximum CA z‐score over time (zMax), and MACE were analyzed. We performed a matched analysis of treatment effect on likelihood of CAA regression. Of 2860 KD patients, 500 (17%) had CAA, including 90 with CAA z‐score >10. Most (91%) received IVIG within 10 days of illness, 32% received >1 IVIG, and 27% received adjunctive anti‐inflammatory medications. CAA regression occurred in 75%. Lack of CAA regression and higher CAA zMax were associated with earlier era, larger CAA z‐score at diagnosis, and bilateral CAA in univariate and multivariable analyses. MACE occurred in 24 (5%) patients and was associated with higher CAA z‐score at diagnosis and lack of IVIG treatment. In a subset of patients (n=132) matched by age at KD and baseline CAA z‐score, those receiving IVIG plus adjunctive medication had a CAA regression rate of 91% compared with 68% for the 3 other groups (IVIG alone, IVIG ≥2 doses, or IVIG ≥2 doses plus adjunctive medication). Conclusions: CAA regression occurred in 75% of patients. CAA z‐score at diagnosis was highly predictive of outcomes, which may be improved by early IVIG treatment and adjunctive therapies.
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    Relationship of white matter network topology and cognitive outcome in adolescents with d-transposition of the great arteries
    (Elsevier, 2015) Panigrahy, Ashok; Schmithorst, Vincent J.; Wisnowski, Jessica L.; Watson, Christopher G.; Bellinger, David C.; Newburger, Jane; Rivkin, Michael
    Patients with congenital heart disease (CHD) are at risk for neurocognitive impairments. Little is known about the impact of CHD on the organization of large-scale brain networks. We applied graph analysis techniques to diffusion tensor imaging (DTI) data obtained from 49 adolescents with dextro-transposition of the great arteries (d-TGA) repaired with the arterial switch operation in early infancy and 29 healthy referent adolescents. We examined whether differences in neurocognitive functioning were related to white matter network topology. We developed mediation models revealing the respective contributions of peri-operative variables and network topology on cognitive outcome. Adolescents with d-TGA had reduced global efficiency at a trend level (p = 0.061), increased modularity (p = 0.012), and increased small-worldness (p = 0.026) as compared to controls. Moreover, these network properties mediated neurocognitive differences between the d-TGA and referent adolescents across every domain assessed. Finally, structural network topology mediated the neuroprotective effect of longer duration of core cooling during reparative neonatal cardiac surgery, as well as the detrimental effects of prolonged hospitalization. Taken together, worse neurocognitive function in adolescents with d-TGA is mediated by global differences in white matter network topology, suggesting that disruption of this configuration of large-scale networks drives neurocognitive dysfunction. These data provide new insights into the interplay between perioperative factors, brain organization, and cognition in patients with complex CHD.
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    Idiopathic Pericarditis and Pericardial Effusion in Children: Contemporary Epidemiology and Management
    (Blackwell Publishing Ltd, 2014) Shakti, Divya; Hehn, Rebecca; Gauvreau, Kimberly; Sundel, Robert; Newburger, Jane
    Background: Multicenter studies on idiopathic or viral pericarditis and pericardial effusion (PPE) have not been reported in children. Colchicine use for PPE in adults is supported. We explored epidemiology and management for inpatient hospitalizations for PPE in US children and risk factors for readmission. Methods and Results: We analyzed patients in the Pediatric Health Information System database for (1) a code for PPE; (2) absence of codes for underlying systemic disease (eg, neoplastic, cardiac, rheumatologic, renal); (3) age ≥30 days and <21 years; and (4) discharge between January 1, 2007, and December 31, 2012, from 38 hospitals contributing complete data for each year of the study period. Among 11 364 hospitalizations with PPE codes during the study period, 543 (4.8%) met entry criteria for idiopathic or viral PPE. Significantly more boys were noted, especially among adolescents. No temporal trends were noted. Median age was 14.5 years (interquartile range 7.3 to 16.6 years); 78 patients (14.4%) underwent pericardiocentesis, 13 (2.4%) underwent pericardiotomy, and 11 (2.0%) underwent pericardiectomy; 157 (28.9%) had an intensive care unit stay, including 2.0% with tamponade. Median hospitalization was 3 days (interquartile range 2 to 4 days). Medications used at initial admission were nonsteroidal anti‐inflammatory drugs (71.3%), corticosteroids (22.7%), aspirin (7.0%), and colchicine (3.9%). Readmissions within 1 year of initial admission occurred in 46 of 447 patients (10.3%), mostly in the first 3 months. No independent predictors of readmission were noted, but our statistical power was limited. Practice variation was noted in medical management and pericardiocentesis. Conclusions: Our report provides the first large multicenter description of idiopathic or viral PPE in children. Idiopathic or viral PPE is most common in male adolescents and is treated infrequently with colchicine.
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    Organizational topology of brain and its relationship to ADHD in adolescents with d‐transposition of the great arteries
    (John Wiley and Sons Inc., 2016) Schmithorst, Vincent J.; Panigrahy, Ashok; Gaynor, J. William; Watson, Christopher G.; Lee, Vince; Bellinger, David C.; Rivkin, Michael; Newburger, Jane
    Abstract Objective: Little is currently known about the impact of congenital heart disease (CHD) on the organization of large‐scale brain networks in relation to neurobehavioral outcome. We investigated whether CHD might impact ADHD symptoms via changes in brain structural network topology in a cohort of adolescents with d‐transposition of the great arteries (d‐TGA) repaired with the arterial switch operation in early infancy and referent subjects. We also explored whether these effects might be modified by apolipoprotein E (APOE) genotype, as the APOE ε2 allele has been associated with worse neurodevelopmental outcomes after repair of d‐TGA in infancy. Methods: We applied graph analysis techniques to diffusion tensor imaging (DTI) data obtained from 47 d‐TGA adolescents and 29 healthy referents to construct measures of structural topology at the global and regional levels. We developed statistical mediation models revealing the respective contributions of d‐TGA, APOE genotype, and structural network topology on ADHD outcome as measured by the Connors ADHD/DSM‐IV Scales (CADS). Results: Changes in overall network connectivity, integration, and segregation mediated worse ADHD outcomes in d‐TGA patients compared to healthy referents; these changes were predominantly in the left and right intrahemispheric regional subnetworks. Exploratory analysis revealed that network topology also mediated detrimental effects of the APOE ε4 allele but improved neurobehavioral outcomes for the APOE ε2 allele. Conclusion: Our results suggest that disruption of organization of large‐scale networks may contribute to neurobehavioral dysfunction in adolescents with CHD and that this effect may interact with APOE genotype.