50 results on '"Jane, Lougheed"'
Search Results
2. Association between maternal marginalization and infants born with congenital heart disease in Ontario Canada
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Qun Miao, Sandra Dunn, Shi Wu Wen, Jane Lougheed, Phoebe Yang, Michael Davies, Carolina Lavin Venegas, and Mark Walker
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Retrospective cohort study ,Mother ,Pregnancy ,Infant ,Congenital heart disease ,Socioeconomic status ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background This study aims to evaluate the impact of socioeconomic status (SES) on the risk of congenital heart disease (CHD) since previous studies have yielded inconsistent results. Methods We conducted a population-based retrospective cohort study, including all singleton live and still births in Ontario hospitals from April 1, 2012, to March 31, 2018. We used linked records from the Better Outcomes Registry & Network Information System, the Canadian Institute for Health Information databases, and the Ontario Marginalization Index (ON_Marg). ON_Marg was estimated at a dissemination area level using Canadian Census 2016 data and categorized into quintiles. Multivariable logistic regression models were performed to examine the relationships between four ON_Marg indices (material deprivation, dependency, ethnic concentration, residential instability), as proxies for maternal SES and the risk of infant CHD. We adjusted for maternal age at birth, assisted reproductive technology, obesity, pre-existing health conditions, substance use during pregnancy, mental health conditions before and during pregnancy, rural residence, and infant’s sex in the analysis. Results Among the cohort of 776,799 singletons, 9,359 infants had a diagnosis of CHD. Of those, 3,069 were severe CHD and 493 cases were single ventricle CHD. The prevalence of all infant CHD types was higher for males relative to females. Compared to mothers living in neighbourhoods with the lowest material deprivation, mothers with highest material deprivation had a 27% (adjusted OR = 1.27; 95% CI: 1.18–1.37) higher odds of having an infant diagnosed with CHD. Mothers living in neighbourhoods with the highest minority ethnic and immigrant concentration tend to have infants with 11% lower odds of CHD (adjusted OR = 0.89; 95% CI: 0.82–0.97) as compared to those living in the least ethnically diverse communities. Maternal dependency and residential stability quintiles were not significantly associated with the risk of CHD. Conclusion Higher maternal material deprivation was associated with increasing odds of infant CHD, whereas neighbourhood minority ethnic concentration was inversely associated with the odds of infant CHD. Our study further confirms that poverty is associated with CHD development. Future investigations might focus on the causal pathways between social deprivation, immigrant status, ethnicity, and the risk of infant CHD.
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- 2023
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3. Impacting Children’s Physical and Mental Health through Kinesiology Support in Clinical Care: A Randomized Controlled Trial Protocol
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Nacera Hanzal, Jenna Yaraskavitch, Patricia E. Longmuir, Anna M. McCormick, Jane Lougheed, Christine Lamontagne, Kristian B. Goulet, Leanne M. Ward, Sherri L. Katz, Marie-Eve Robinson, Lesleigh S. Abbott, Thomas A. Kovesi, John J. Reisman, Daniela Pohl, and Hana Alazem
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physical activity disability ,pediatric ,physical functioning ,chronic medical condition ,Sports medicine ,RC1200-1245 - Abstract
Objectives To enhance the confidence of children and adolescents with medical conditions and disabilities to engage in healthy, active lifestyles. Children with medical conditions and disabilities often exhibit more sedentary lifestyles relative to peers and are at increased risk of poor health outcomes. Clinical experience suggests physical activity confidence is an important factor influencing physical activity participation. Methods This randomized controlled trial evaluates an evidence-based intervention targeting physical activity confidence among children and adolescents with medical conditions and disabilities. Potential participants, 8 to 18 years of age diagnosed with a medical condition or disability, will be screened for adequate physical activity motivation but a lack confidence. Consenting participants (n=128) will be randomized 1:1 to a 12-week in-person or virtual physical activity intervention (24 hours/week total) led by a Registered Kinesiologist or control (assessments only). The intervention will combine physical activity participation with education about physical activity knowledge, goal setting, motivation and self-management. Primary outcomes are self-reported physical activity confidence and motivation at baseline, post-intervention and three months following intervention completion. A secondary outcome will be daily physical activity minutes assessed by accelerometry. A repeated measures mixed model will be used to compare outcomes between the in-person intervention, virtual intervention, and control groups (alpha=0.05). Conclusions This trial aims to assess the impact of a novel application of behaviour change theory on physical activity confidence among children and adolescents living with medical conditions or disabilities. Increased physical activity confidence, knowledge and skills could enable these youth to lead a more active lifestyle.
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- 2023
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4. Associations of congenital heart disease with deprivation index by rural-urban maternal residence: a population-based retrospective cohort study in Ontario, Canada
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Qun Miao, Sandra Dunn, Shi Wu Wen, Jane Lougheed, Fayza Sharif, and Mark Walker
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The BORN database ,The Canadian Institute for Health Information Discharge Abstract Database and National Ambulatory Care Reporting System database ,Congenital heart disease ,Social-economic status ,Maternal deprivation index ,Social deprivation index ,Pediatrics ,RJ1-570 - Abstract
Abstract Background The risk of congenital heart disease (CHD) has been found to vary by maternal socioeconomic status (SES) and rural-urban residence. In this study, we examined associations of CHD with two maternal SES indicators and stratified the analysis by maternal rural-urban residence. Methods This was a population-based retrospective cohort study. We included all singleton stillbirths and live hospital births from April 1, 2012 to March 31, 2018 in Ontario, Canada. We linked the BORN Information System and Canadian Institute for Health Information databases. Multivariable logistic regression models were used to examine associations of CHD with material deprivation index (MDI), social deprivation index (SDI), and maternal residence while adjusting for maternal age at birth, assisted reproductive technology, obesity, pre-pregnancy maternal health conditions, mental health illness before and during pregnancy, substance use during pregnancy, and infant’s sex. MDI and SDI were estimated at a dissemination area level in Ontario and were categorized into quintiles (Q1-Q5). Results This cohort study included 798,173 singletons. In maternal urban residence, the p trend (Cochran–Armitage test) was less than 0.0001 for both MDI and SDI; while for rural residence, it was 0.002 and 0.98, respectively. Infants living in the most materially deprived neighbourhoods (MDI Q5) had higher odds of CHD (aOR: 1.21, 95% CI: 1.12–1.29) compared to Q1. Similarly, infants living in the most socially deprived neighbourhoods (SDI Q5) had an 18% increase in the odds of CHD (aOR: 1.18, 95% CI: 1.1–1.26) compared to Q1. Rural infants had a 13% increase in the odds of CHD compared to their urban counterparts. After stratifying by maternal rural-urban residence, we still detected higher odds of CHD with two indices in urban residence but only MDI in rural residence. Conclusion Higher material and social deprivation and rural residence were associated with higher odds of CHD. Health interventions and policies should reinforce the need for optimal care for all families, particularly underprivileged families in both rural and urban regions. Future studies should further investigate the effect of social deprivation on the risk of CHD development.
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- 2022
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5. Whole genome sequencing delineates regulatory, copy number, and cryptic splice variants in early onset cardiomyopathy
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Robert Lesurf, Abdelrahman Said, Oyediran Akinrinade, Jeroen Breckpot, Kathleen Delfosse, Ting Liu, Roderick Yao, Gabrielle Persad, Fintan McKenna, Ramil R. Noche, Winona Oliveros, Kaia Mattioli, Shreya Shah, Anastasia Miron, Qian Yang, Guoliang Meng, Michelle Chan Seng Yue, Wilson W. L. Sung, Bhooma Thiruvahindrapuram, Jane Lougheed, Erwin Oechslin, Tapas Mondal, Lynn Bergin, John Smythe, Shashank Jayappa, Vinay J. Rao, Jayaprakash Shenthar, Perundurai S. Dhandapany, Christopher Semsarian, Robert G. Weintraub, Richard D. Bagnall, Jodie Ingles, Genomics England Research Consortium, Marta Melé, Philipp G. Maass, James Ellis, Stephen W. Scherer, and Seema Mital
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Medicine ,Genetics ,QH426-470 - Abstract
Abstract Cardiomyopathy (CMP) is a heritable disorder. Over 50% of cases are gene-elusive on clinical gene panel testing. The contribution of variants in non-coding DNA elements that result in cryptic splicing and regulate gene expression has not been explored. We analyzed whole-genome sequencing (WGS) data in a discovery cohort of 209 pediatric CMP patients and 1953 independent replication genomes and exomes. We searched for protein-coding variants, and non-coding variants predicted to affect the function or expression of genes. Thirty-nine percent of cases harbored pathogenic coding variants in known CMP genes, and 5% harbored high-risk loss-of-function (LoF) variants in additional candidate CMP genes. Fifteen percent harbored high-risk regulatory variants in promoters and enhancers of CMP genes (odds ratio 2.25, p = 6.70 × 10−7 versus controls). Genes involved in α-dystroglycan glycosylation (FKTN, DTNA) and desmosomal signaling (DSC2, DSG2) were most highly enriched for regulatory variants (odds ratio 6.7–58.1). Functional effects were confirmed in patient myocardium and reporter assays in human cardiomyocytes, and in zebrafish CRISPR knockouts. We provide strong evidence for the genomic contribution of functionally active variants in new genes and in regulatory elements of known CMP genes to early onset CMP.
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- 2022
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6. To Be or Not to Be: Surviving Immune‐Mediated Fetal Heart Disease
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Edgar Jaeggi, Lisa Hornberger, Bettina Cuneo, Anita J. Moon‐Grady, Marie‐Josée Raboisson, Jane Lougheed, Karim Diab, Wadi Mawad, and Earl Silverman
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Published
- 2022
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7. Children with Cardiomyopathy have Active Lifestyles Despite Reporting Disease-Specific Barriers to Physical Activity: A Mixed-Methods Study
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Kevin Moncion, Letizia Gardin, Jane Lougheed, Kristi Adamo, and Patricia E. Longmuir
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physical activity ,exercise physiology ,pediatric cardiomyopathy ,mixed methodology ,Sports medicine ,RC1200-1245 - Abstract
OBJECTIVES This exploratory mixed-methods study explored the barriers to physical activity, daily physical activity and submaximal exercise capacity among children with and at risk for cardiomyopathy and children with atrial septal defects. METHODS The study followed a convergent parallel mixed methodology design. Semi-structured interviews explored physical activity barriers. Seven-day accelerometry assessed moderate-to-vigorous physical activity, and an intermittent cardiopulmonary exercise test measured submaximal exercise capacity. RESULTS Twenty children, including 5 with cardiomyopathy (n=2 females, 14.2 ± 2.7 years old), 7 who were genotype-positive phenotype-negative for cardiomyopathy (n=5 females, 10.6 ± 3.3 years old) and 8 with atrial septal defects (n=4 females, 9.4 ± 3.8 years old) were recruited. Children with cardiomyopathy reported disease-specific physical activity barriers, while children who were genotype-positive phenotype-negative perceived barriers related to lack of time, parent support or activity motivation. The average daily moderate-to-vigorous physical activity was less than the recommended 60-minutes/day (n=20, mean 48.1 ± 18.0 minutes). Children with cardiomyopathy participated a median of 141.2 [interquartile range (IQR): 98.8) minutes of light-intensity physical activity and a median of 55.6 (IQR: 34.6) minutes of moderate-to-vigorous physical activity. The average submaximal exercise capacity was low (n=16, 25.2 ± 5.7 mL/kg/min). Estimated submaximal exercise capacity, including metabolic equivalent (4.5 ± 3.1 METs), respiratory exchange ratio (median = 1.0, IQR: 0.09) and ratings of perceived exertion (median = 7, IQR: 5) at peak exercise suggest that children with cardiomyopathy appear to have the exercise capacity to participate in low-to-moderate intensity activities. CONCLUSIONS These novel data suggest that a diagnosis of cardiomyopathy may not preclude children from participating in a healthy, active lifestyle. However, they perceive disease-specific physical activity barriers and may require support to optimize their level of participation for optimal health.
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- 2022
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8. Neighbourhood maternal socioeconomic status indicators and risk of congenital heart disease
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Qun Miao, Sandra Dunn, Shi Wu Wen, Jane Lougheed, Jessica Reszel, Carolina Lavin Venegas, and Mark Walker
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The Better Outcomes Registry & Network (BORN) database ,The Canadian Institute for Health Information Discharge Abstract Database (CIHI-DAD) ,Congenital heart disease ,Socioeconomic status ,Immigrants ,Minorities ,Gynecology and obstetrics ,RG1-991 - Abstract
Abstract Background This study aimed to examine the relationships between various maternal socioeconomic status (SES) indicators and the risk of congenital heart disease (CHD). Methods This was a population-based retrospective cohort study, including all singleton stillbirths and live births in Ontario hospitals from April 1, 2012 to March 31, 2018. Multivariable logistic regression models were performed to examine the relationships between maternal neighbourhood household income, poverty, education level, employment and unemployment status, immigration and minority status, and population density and the risk of CHD. All SES variables were estimated at a dissemination area level and categorized into quintiles. Adjustments were made for maternal age at birth, assisted reproductive technology, obesity, pre-existing maternal health conditions, substance use during pregnancy, rural or urban residence, and infant’s sex. Results Of 804,292 singletons, 9731 (1.21%) infants with CHD were identified. Compared to infants whose mothers lived in the highest income neighbourhoods, infants whose mothers lived in the lowest income neighbourhoods had higher likelihood of developing CHD (adjusted OR: 1.29, 95% CI: 1.20–1.38). Compared to infants whose mothers lived in the neighbourhoods with the highest percentage of people with a university or higher degree, infants whose mothers lived in the neighbourhoods with the lowest percentage of people with university or higher degree had higher chance of CHD (adjusted OR: 1.34, 95% CI: 1.24–1.44). Compared to infants whose mothers lived in the neighbourhoods with the highest employment rate, the odds of infants whose mothers resided in areas with the lowest employment having CHD was 18% higher (adjusted OR: 1.18, 95% CI: 1.10–1.26). Compared to infants whose mothers lived in the neighbourhoods with the lowest proportion of immigrants or minorities, infants whose mothers resided in areas with the highest proportions of immigrants or minorities had 18% lower odds (adjusted OR: 0.82, 95% CI: 0.77–0.88) and 16% lower odds (adjusted OR: 0.84, 95% CI: 0.78–0.91) of CHD, respectively. Conclusion Lower maternal neighbourhood household income, poverty, lower educational level and unemployment status had positive associations with CHD, highlighting a significant social inequity in Ontario. The findings of lower CHD risk in immigrant and minority neighbourhoods require further investigation.
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- 2021
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9. Prevention of post-cardiac surgery vitamin D deficiency in children with congenital heart disease: a pilot feasibility dose evaluation randomized controlled trial
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James Dayre McNally, Katie O’Hearn, Dean A. Fergusson, Jane Lougheed, Dermot R. Doherty, Gyaandeo Maharajh, Hope Weiler, Glenville Jones, Ali Khamessan, Stephanie Redpath, Pavel Geier, Lauralyn McIntyre, Margaret L. Lawson, Tara Girolamo, Kusum Menon, and on behalf of the Canadian Critical Care Trials Group
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Vitamin D deficiency ,Congenital heart disease ,Critical care ,Pediatric intensive care unit ,Cholecalciferol ,High-dose ,Medicine (General) ,R5-920 - Abstract
Abstract Background The vast majority of children undergoing cardiac surgery have low vitamin D levels post-operative, which may contribute to greater illness severity and worse clinical outcomes. Prior to the initiation of a large phase III clinical trial focused on clinical outcomes, studies are required to evaluate the feasibility of the study protocol, including whether the proposed dosing regimen can safely prevent post-operative vitamin D deficiency in this high-risk population. Methods We conducted a two-arm, double-blind dose evaluation randomized controlled trial in children requiring cardiopulmonary bypass for congenital heart disease. Pre-operatively, participants were randomized to receive cholecalciferol representing usual care (< 1 year = 400 IU/day, > 1 year = 600 IU/day) or a higher dose approximating the Institute of Medicine tolerable upper intake level (< 1 year = 1600 IU/day, > 1 year = 2400 IU/day). The feasibility outcomes were post-operative vitamin D status (primary), vitamin D-related adverse events, accrual rate, study withdrawal rate, blinding, and protocol non-adherence. Results Forty-six children were randomized, and five withdrew prior to surgery, leaving 41 children (21 high dose, 20 usual care) in the final analysis. The high dose group had higher 25-hydroxyvitamin D concentrations both intraoperatively (mean difference + 25.9 nmol/L; 95% CI 8.3–43.5) and post-operatively (mean difference + 17.2 nmol/L; 95% CI 5.5–29.0). Fewer participants receiving high-dose supplementation had post-operative serum 25-hydroxyvitamin D concentrations under 50 nmol/L, compared with usual care (RR 0.31, 95% CI 0.11–0.87). Post-operative vitamin D status was associated with the treatment arm and the number of doses received. There were no cases of hypercalcemia, and no significant adverse events related to vitamin D. While only 75% of the target sample size was recruited (limited funding), the consent rate (83%), accrual rate (1.5 per site month), number of withdrawals (11%), and ability to maintain blinding support feasibility of a larger trial. Conclusions Pre-operative daily high-dose supplementation improved vitamin D status pre-operatively and at time of pediatric ICU admission. The protocol for a more definitive trial should limit enrollment of children with at least 30 days between randomization and surgery to allow adequate duration of supplementation or consider a loading dose. Trial registration ClinicalTrials.gov, NCT01838447 . Registered on April 24, 2013
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- 2020
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10. Outcome of Antibody‐Mediated Fetal Heart Disease With Standardized Anti‐Inflammatory Transplacental Treatment
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Wadi Mawad, Lisa Hornberger, Bettina Cuneo, Marie‐Josée Raboisson, Anita J. Moon‐Grady, Jane Lougheed, Karim Diab, Julia Parkman, Earl Silverman, and Edgar Jaeggi
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cardiomyopathy ,fetal ,heart block ,outcome ,steroids ,treatment ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background Transplacental fetal treatment of immune‐mediated fetal heart disease, including third‐degree atrioventricular block (AVB III) and endocardial fibroelastosis, is controversial. Methods and Results To study the impact of routine transplacental fetal treatment, we reviewed 130 consecutive cases, including 108 with AVB III and 22 with other diagnoses (first‐degree/second‐degree atrioventricular block [n=10]; isolated endocardial fibroelastosis [n=9]; atrial bradycardia [n=3]). Dexamethasone was started at a median of 22.4 gestational weeks. Additional treatment for AVB III included the use of a β‐agonist (n=47) and intravenous immune globulin (n=34). Fetal, neonatal, and 1‐year survival rates with AVB III were 95%, 93%, and 89%, respectively. Variables present at diagnosis that were associated with perinatal death included an atrial rate
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- 2022
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11. Association of maternal socioeconomic status and race with risk of congenital heart disease: a population-based retrospective cohort study in Ontario, Canada
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Mark Walker, Jessica Reszel, Shi Wu Wen, Sandra Dunn, Cynthia Maxwell, Qun Miao, Jane Lougheed, and Kaamel Hafizi
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Medicine - Published
- 2022
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12. Return of genetic and genomic research findings: experience of a pediatric biorepository
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Tanya Papaz, Eriskay Liston, Laura Zahavich, Dimitri J. Stavropoulos, Rebekah K. Jobling, Raymond H. Kim, Miriam Reuter, Anastasia Miron, Erwin Oechslin, Tapas Mondal, Lynn Bergin, John F. Smythe, Luis Altamirano-Diaz, Jane Lougheed, Roderick Yao, Oyediran Akinrinade, Jeroen Breckpot, and Seema Mital
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Return of research findings ,Genome sequencing ,Primary findings ,Cost of return ,Navigating return ,Internal medicine ,RC31-1245 ,Genetics ,QH426-470 - Abstract
Abstract Background Assess process, uptake, validity and resource needs for return of actionable research findings to biobank participants. Methods Participants were prospectively enrolled in a multicenter biorepository of childhood onset heart disease. Clinically actionable research findings were reviewed by a Return of Research Results Committee (RRR) and returned to the physician or disclosed directly to the participant through a research genetic counselor. Action taken following receipt of this information was reviewed. Results Genetic data was generated in 1963 of 7408 participants. Fifty-nine new findings were presented to the RRR committee; 20 (34%) were deemed reportable. Twelve were returned to the physician, of which 7 were disclosed to participants (median time to disclosure, 192 days). Seven findings were returned to the research genetic counselor; all have been disclosed (median time to disclosure, 19 days). Twelve families (86%) opted for referral to clinical genetics after disclosure of findings; 7 results have been validated, 5 results are pending. Average cost of return and disclosure per reportable finding incurred by the research program was $750 when utilizing a research genetic counselor; clinical costs associated with return were not included. Conclusions Return of actionable research findings was faster if disclosed directly to the participant by a research genetic counselor. There was a high acceptability amongst participants for receiving the findings, for referral to clinical genetics, and for clinical validation of research findings, with all referred cases being clinically confirmed.
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- 2019
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13. Pedometer Efficacy for Clinical Care in Pediatric Cardiology
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Angelica Blais, Patricia E. Longmuir, and Jane Lougheed
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Orthopedics and Sports Medicine - Abstract
Background: Physical activity is essential to the long-term health of children living with cardiac disease. The simplicity and cost of pedometers make them an attractive alternative to accelerometers for monitoring the physical activity behaviors of these children. This study compared measures obtained from commercial-grade pedometers and accelerometers. Methods: Pediatric cardiology outpatients (n = 41, mean age = 8.4 [3.7] y, 61% female) wore a pedometer and accelerometer daily for 1 week. Step counts and minutes of moderate to vigorous physical activity were compared between devices, accounting for age group, sex, and diagnostic severity, using univariate analysis of variance. Results: While pedometer data were significantly correlated with accelerometers (r > .74, P P ). For step counts, there was a significant age by sex interaction observed where preschool and adolescent males tended to have greater differences between accelerometer and step count data than females (P ). Differences between devices were not associated with severity of diagnosis. Conclusions: The distribution of pedometers in a pediatric outpatient clinic was feasible, yet the data collected significantly overestimated physical activity, especially among younger children. Practitioners who want to introduce objective measurements as part of their physical activity counseling practice should use pedometers to monitor individual changes in physical activity and consider patient age before administering these devices for clinical care.
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- 2023
14. Participation in a Community-Based Sport Program is Feasible for Children with Congenital Heart Disease and May Benefit Physical Literacy Development: A Pilot Study
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Angelica Z. Blais, Jane Lougheed, Kristi B. Adamo, and Patricia E. Longmuir
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developmental delay ,motor development ,movement skill ,muscular endurance ,physical activity ,Sports medicine ,RC1200-1245 - Abstract
OBJECTIVES Children with congenital heart disease (CHD) often lack confidence and demonstrate limited movement skills during physical activity. Community-based sport programs have been suggested to build their confidence and competence. This study examined the feasibility and physical literacy impact of an existing community-based sport program for children with moderate to complex CHD. METHODS This pilot study employed a parallel mixed method, single-case experimental design to evaluate the feasibility and impact of a weekly, community-based sport intervention (Sportball©). Intervention field notes and focus group transcripts were analysed deductively to inform feasibility. Physical literacy outcomes were measured using the Canadian Assessment of Physical Literacy. Paired t-tests examined changes in physical literacy scores, while qualitative data informed perceived changes in physical literacy tasks. RESULTS Participants (n=11, 45% female) were 8.2 ± 1.2 years. Nine children completed >80% of the 1-hour Sportball© sessions (10 lessons total). No adverse events occurred during or as a result of the intervention. Enabling participants to recognize the sensations of exercise and whether or not they needed to rest, designing activities and instructions to mitigate the risk of body contact, and accommodating the needs of participants with developmental/attentional limitations were important factors embedded into the design of the program, contributing to its feasibility. Participants reported perceived improvements in movement skill and torso endurance/strength, changes which were reflected in the objective physical literacy measures (movement skill: ∆ mean= 2.0 ± 0.98 points, p=0.07, r=0.57; torso endurance/strength: ∆ mean= 5.27 ± 7.20 seconds, p=0.44, r=0.26). CONCLUSIONS The Sportball© intervention was feasible for children with CHD, including those with activity restrictions or developmental delays. Children enjoyed the program and wanted it to continue. Measurable improvements in movement skill and muscular endurance were recognized by participants. Future trials evaluating Sportball©’s impact with larger samples and multiple 10-week sessions are recommended.
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- 2020
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15. In Utero Enzyme-Replacement Therapy for Infantile-Onset Pompe's Disease
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Jennifer L. Cohen, Pranesh Chakraborty, Karen Fung-Kee-Fung, Marisa E. Schwab, Deeksha Bali, Sarah P. Young, Michael H. Gelb, Hamid Khaledi, Alicia DiBattista, Stacey Smallshaw, Felipe Moretti, Derek Wong, Catherine Lacroix, Dina El Demellawy, Kyle C. Strickland, Jane Lougheed, Anita Moon-Grady, Billie R. Lianoglou, Paul Harmatz, Priya S. Kishnani, and Tippi C. MacKenzie
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Glycogen Storage Disease Type II ,Humans ,Infant ,General Medicine - Abstract
Patients with early-onset lysosomal storage diseases are ideal candidates for prenatal therapy because organ damage starts in utero. We report the safety and efficacy results of in utero enzyme-replacement therapy (ERT) in a fetus with CRIM (cross-reactive immunologic material)-negative infantile-onset Pompe's disease. The family history was positive for infantile-onset Pompe's disease with cardiomyopathy in two previously affected deceased siblings. After receiving in utero ERT and standard postnatal therapy, the current patient had normal cardiac and age-appropriate motor function postnatally, was meeting developmental milestones, had normal biomarker levels, and was feeding and growing well at 13 months of age.
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- 2022
16. Neighbourhood maternal socioeconomic status indicators and risk of congenital heart disease
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Jane Lougheed, Jessica Reszel, Qun Miao, Carolina Lavin Venegas, Shi Wu Wen, Sandra Dunn, and Mark Walker
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Adult ,Heart Defects, Congenital ,Male ,Population ,Mothers ,Logistic regression ,lcsh:Gynecology and obstetrics ,Odds ,Young Adult ,Residence Characteristics ,Risk Factors ,Immigrants ,medicine ,Humans ,education ,Poverty ,Socioeconomic status ,Neighbourhood (mathematics) ,lcsh:RG1-991 ,Retrospective Studies ,Congenital heart disease ,Minorities ,Ontario ,education.field_of_study ,Pregnancy ,business.industry ,Infant, Newborn ,Infant ,Obstetrics and Gynecology ,Health Status Disparities ,medicine.disease ,The Canadian Institute for Health Information Discharge Abstract Database (CIHI-DAD) ,Socioeconomic Factors ,Child, Preschool ,The Better Outcomes Registry & Network (BORN) database ,Household income ,Female ,business ,Research Article ,Demography - Abstract
Background This study aimed to examine the relationships between various maternal socioeconomic status (SES) indicators and the risk of congenital heart disease (CHD). Methods This was a population-based retrospective cohort study, including all singleton stillbirths and live births in Ontario hospitals from April 1, 2012 to March 31, 2018. Multivariable logistic regression models were performed to examine the relationships between maternal neighbourhood household income, poverty, education level, employment and unemployment status, immigration and minority status, and population density and the risk of CHD. All SES variables were estimated at a dissemination area level and categorized into quintiles. Adjustments were made for maternal age at birth, assisted reproductive technology, obesity, pre-existing maternal health conditions, substance use during pregnancy, rural or urban residence, and infant’s sex. Results Of 804,292 singletons, 9731 (1.21%) infants with CHD were identified. Compared to infants whose mothers lived in the highest income neighbourhoods, infants whose mothers lived in the lowest income neighbourhoods had higher likelihood of developing CHD (adjusted OR: 1.29, 95% CI: 1.20–1.38). Compared to infants whose mothers lived in the neighbourhoods with the highest percentage of people with a university or higher degree, infants whose mothers lived in the neighbourhoods with the lowest percentage of people with university or higher degree had higher chance of CHD (adjusted OR: 1.34, 95% CI: 1.24–1.44). Compared to infants whose mothers lived in the neighbourhoods with the highest employment rate, the odds of infants whose mothers resided in areas with the lowest employment having CHD was 18% higher (adjusted OR: 1.18, 95% CI: 1.10–1.26). Compared to infants whose mothers lived in the neighbourhoods with the lowest proportion of immigrants or minorities, infants whose mothers resided in areas with the highest proportions of immigrants or minorities had 18% lower odds (adjusted OR: 0.82, 95% CI: 0.77–0.88) and 16% lower odds (adjusted OR: 0.84, 95% CI: 0.78–0.91) of CHD, respectively. Conclusion Lower maternal neighbourhood household income, poverty, lower educational level and unemployment status had positive associations with CHD, highlighting a significant social inequity in Ontario. The findings of lower CHD risk in immigrant and minority neighbourhoods require further investigation.
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- 2021
17. Machine Learning Identifies Clinical and Genetic Factors Associated With Anthracycline Cardiotoxicity in Pediatric Cancer Survivors
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Marie A. Chaix, James Ellis, Cedric Manlhiot, Emily Lam, Paul C. Nathan, Neha Parmar, Anne Christie, Jane Lougheed, Paul F. Kantor, Guoliang Meng, Luc Mertens, Anastasia Miron, Leonard S. Sender, Stacey Marjerrison, Shayna Zelcer, Ashok Kumar Manickaraj, David C. Hodgson, Rejane Dillenburg, Seema Mital, Oyediran Akinrinade, Herschel Rosenberg, Roderick Yao, Caroline Kinnear, Myriam Lafreniere-Roula, Mylene Bassal, and Pediatrics
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H2AX, H2A family member X ,Oncology ,Cardiac & Cardiovascular Systems ,PREDICTION ,VARIANT ,Cardiomyopathy ,DMSO, dimethyl sulfoxide ,THERAPY ,Pediatrics ,LVEF - Left ventricular ejection fraction ,AUC, area under the curve ,risk prediction ,GSEA, gene set enrichment analysis ,IC50, half-maximal inhibitory concentration ,TUMOR ,LVEF, left ventricular ejection fraction ,echocardiography ,Genetic risk ,Original Research ,mRNA, messenger RNA ,PGP, Personal Genome Project ,RF, random forest ,machine learning ,Cardiology and Cardiovascular Medicine ,Life Sciences & Biomedicine ,Clinical risk factor ,Cancer survivorship ,SKAT, sequence kernel association test ,medicine.medical_specialty ,DOXORUBICIN ,Anthracycline ,MAF, minor allele frequency ,anthracycline ,MECHANISMS ,Internal medicine ,genomics ,medicine ,GENOME-WIDE ASSOCIATION ,LV, left ventricular ,SNV, single-nucleotide variant ,Cardiotoxicity ,Science & Technology ,CARDIOMYOPATHY ,hiPSC-CM, human induced pluripotent stem cell–derived cardiomyocyte ,business.industry ,medicine.disease ,DOX, doxorubicin ,Pediatric cancer ,CI, confidence interval ,OR, odds ratio ,cancer survivorship ,Cardiovascular System & Cardiology ,RISK-FACTORS ,business ,cardiomyopathy - Abstract
Background Despite known clinical risk factors, predicting anthracycline cardiotoxicity remains challenging. Objectives This study sought to develop a clinical and genetic risk prediction model for anthracycline cardiotoxicity in childhood cancer survivors. Methods We performed exome sequencing in 289 childhood cancer survivors at least 3 years from anthracycline exposure. In a nested case-control design, 183 case patients with reduced left ventricular ejection fraction despite low-dose doxorubicin (≤250 mg/m2), and 106 control patients with preserved left ventricular ejection fraction despite doxorubicin >250 mg/m2 were selected as extreme phenotypes. Rare/low-frequency variants were collapsed to identify genes differentially enriched for variants between case patients and control patients. The expression levels of 5 top-ranked genes were evaluated in human induced pluripotent stem cell–derived cardiomyocytes, and variant enrichment was confirmed in a replication cohort. Using random forest, a risk prediction model that included genetic and clinical predictors was developed. Results Thirty-one genes were differentially enriched for variants between case patients and control patients (p < 0.001). Only 42.6% case patients harbored a variant in these genes compared to 89.6% control patients (odds ratio: 0.09; 95% confidence interval: 0.04 to 0.17; p = 3.98 × 10–15). A risk prediction model for cardiotoxicity that included clinical and genetic factors had a higher prediction accuracy and lower misclassification rate compared to the clinical-only model. In vitro inhibition of gene-associated pathways (PI3KR2, ZNF827) provided protection from cardiotoxicity in cardiomyocytes. Conclusions Our study identified variants in cardiac injury pathway genes that protect against cardiotoxicity and informed the development of a prediction model for delayed anthracycline cardiotoxicity, and it also provided new targets in autophagy genes for the development of cardio-protective drugs. (Preventing Cardiac Sequelae in Pediatric Cancer Survivors [PCS2]; NCT01805778), Central Illustration
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- 2020
18. Prenatal Diagnosis of Transposition of the Great Arteries Reduces Postnatal Mortality: A Population-Based Study
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Michael J. Grattan, Edgar Jaeggi, Tapas Mondal, Lauren Glick, Jane Lougheed, Varsha Thakur, Steven M. Schwartz, and Hazumu Nagata
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Male ,medicine.medical_specialty ,Delayed Diagnosis ,Transposition of Great Vessels ,Improved survival ,Prenatal diagnosis ,030204 cardiovascular system & hematology ,Outcome and Process Assessment ,Pediatrics ,Tertiary care ,Ultrasonography, Prenatal ,Tertiary Care Centers ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Infant Mortality ,medicine ,Prenatal ,Humans ,030212 general & internal medicine ,Ultrasonography ,Ontario ,Obstetrics ,business.industry ,Respiration ,Infant, Newborn ,Infant ,Newborn ,Respiration, Artificial ,Survival Analysis ,Health Care ,Arterial Switch Operation ,Population based study ,Neonatal Malformation ,Perinatal Care ,Outcome and Process Assessment, Health Care ,Great arteries ,Artificial ,Cohort ,Female ,Detection rate ,Cardiology and Cardiovascular Medicine ,business - Abstract
Transposition of the great arteries (TGA) may present as a life-threatening neonatal malformation. Although prenatal detection facilitates the perinatal management, the impact on outcome is controversial.This study reviewed the differences in prenatal diagnosis of TGA from 2009 to 2014 among the 5 geographic areas in Ontario and compared the management, morbidity, and mortality among neonates with a prenatal (prenatal cohort; n = 70) vs a postnatal (postnatal cohort; n = 76) anomaly diagnosis. Cases were identified from prospective databases of the provincial cardiac tertiary centres and the coroner's office.Prenatal TGA detection rates varied significantly among areas (median: 50%; range: 14% to 72%; P = 0.03). Compared with the postnatal cohort, time from birth to tertiary care admission (1.4 vs 10.4 hours, P0.001), prostaglandin therapy (0.1 vs 5.3 hours; P0.001), balloon atrial septostomy (5.3 vs 14.9 hours; P0.001), and arterial switch operation (6 vs 9 days, P = 0.002) was significantly shorter in the prenatal cohort. Although other preoperative variables-including the need of ventilation and mechanical support, morbidity score, and lowest pH and preductal oxygen saturations-were comparable, a prenatal diagnosis was associated with improved 1-year survival (odds ratio: 0.108; 95% confidence interval, 0.013-0.88; P = 0.0184).Prenatal diagnosis of TGA significantly shortened time intervals from birth to neonatal care and surgery and was associated with improved survival. The prenatal detection rate of TGA in Ontario was low (50% or less) outside of Metropolitan Toronto, suggesting the need for new strategies to further improve intraprovincial detection rates.
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- 2020
19. Whole genome sequencing delineates regulatory, copy number, and cryptic splice variants in early onset cardiomyopathy
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Robert, Lesurf, Abdelrahman, Said, Oyediran, Akinrinade, Jeroen, Breckpot, Kathleen, Delfosse, Ting, Liu, Roderick, Yao, Gabrielle, Persad, Fintan, McKenna, Ramil R, Noche, Winona, Oliveros, Kaia, Mattioli, Shreya, Shah, Anastasia, Miron, Qian, Yang, Guoliang, Meng, Michelle Chan Seng, Yue, Wilson W L, Sung, Bhooma, Thiruvahindrapuram, Jane, Lougheed, Erwin, Oechslin, Tapas, Mondal, Lynn, Bergin, John, Smythe, Shashank, Jayappa, Vinay J, Rao, Jayaprakash, Shenthar, Perundurai S, Dhandapany, Christopher, Semsarian, Robert G, Weintraub, Richard D, Bagnall, Jodie, Ingles, Marta, Melé, Philipp G, Maass, James, Ellis, Stephen W, Scherer, M, Zarowiecki, and Barcelona Supercomputing Center
- Subjects
Genetics & Heredity ,RISK ,Informàtica::Aplicacions de la informàtica::Bioinformàtica [Àrees temàtiques de la UPC] ,Science & Technology ,Genetic testing ,Cardiomyopathy ,FUKUTIN GENE ,MEDICAL GENETICS ,ASSOCIATION ,AMERICAN-COLLEGE ,DILATED CARDIOMYOPATHY ,Paediatric research ,CLASSIFICATION ,Gene regulation ,carbohydrates (lipids) ,JOINT CONSENSUS RECOMMENDATION ,Genòmica ,RESOURCE ,Genetics ,TRANSCRIPTION FACTOR ,Gene expression ,Life Sciences & Biomedicine ,Molecular Biology ,Genetics (clinical) ,Genetic diseases - Abstract
Cardiomyopathy (CMP) is a heritable disorder. Over 50% of cases are gene-elusive on clinical gene panel testing. The contribution of variants in non-coding DNA elements that result in cryptic splicing and regulate gene expression has not been explored. We analyzed whole-genome sequencing (WGS) data in a discovery cohort of 209 pediatric CMP patients and 1953 independent replication genomes and exomes. We searched for protein-coding variants, and non-coding variants predicted to affect the function or expression of genes. Thirty-nine percent of cases harbored pathogenic coding variants in known CMP genes, and 5% harbored high-risk loss-of-function (LoF) variants in additional candidate CMP genes. Fifteen percent harbored high-risk regulatory variants in promoters and enhancers of CMP genes (odds ratio 2.25, p = 6.70 × 10−7 versus controls). Genes involved in α-dystroglycan glycosylation (FKTN, DTNA) and desmosomal signaling (DSC2, DSG2) were most highly enriched for regulatory variants (odds ratio 6.7–58.1). Functional effects were confirmed in patient myocardium and reporter assays in human cardiomyocytes, and in zebrafish CRISPR knockouts. We provide strong evidence for the genomic contribution of functionally active variants in new genes and in regulatory elements of known CMP genes to early onset CMP. This project was supported by the Ted Rogers Centre for Heart Research (SM, JE), the Canadian Institutes of Health Research (PJT 175034) (SM, JE) and by the Canadian Institutes of Health Research (ENP 161429), under the frame of ERA PerMed (SM). SM holds the Heart and Stroke Foundation of Canada & Robert M Freedom Chair in Cardiovascular Science. SWS holds the GlaxoSmithKline Endowed Chair in Genome Sciences at the Hospital for Sick Children and the University of Toronto. PGM holds a Canada Research Chair Tier 2 in Non-coding Disease Mechanisms. PGM acknowledges the support of the Government of Canada’s New Frontiers in Research Fund (NFRF), [NFRFE-2018-01305]. EO holds the Bitove Family Professorship of Adult Congenital Heart Disease. MM holds a Ramon y Cajal grant from the Spanish Ministry of Science and Innovation (RYC-2017-22249). WO is supported by funding from Fundació La Marató (321/C/2019). JB is funded by a Frans Van de Werf fellowship for clinical cardiovascular research, and by a senior clinical investigator fellowship of the FWO Flanders. KM was a National Science Foundation Graduate Research Fellow under grant no. DGE1144152 during the majority of the project. CS is the recipient of a National Health and Medical Research Council (NHMRC) Practitioner Fellowship (1154992). JI is the recipient of an NHMRC Career Development Fellowship (1162929). RDB is the recipient of a New South Wales Health Cardiovascular Disease Senior Scientist Grant. PSD is supported by the DBT/Wellcome Trust- Indian Alliance. We acknowledge the Labatt Family Heart Centre Biobank at the Hospital for Sick Children for access to DNA samples, and The Centre for Applied Genomics at the Hospital for Sick Children for performing WGS. We thank Xiucheng Cui and Emanuela Pannia for performing the zebrafish experiments at the SickKids Zebrafish Genetics and Disease Models Core (CRISPR-Cas9 and gRNA syntheses, zebrafish embryo microinjections, gRNA PCR validation, qRT-PCR, cardiac imaging). This research was made possible through access to the data and findings generated by the 100,000 Genomes Project. The 100,000 Genomes Project is managed by Genomics England Limited (a wholly owned company of the Department of Health and Social Care). The 100,000 Genomes Project is funded by the National Institute for Health Research and NHS England. The Wellcome Trust, Cancer Research UK and the Medical Research Council have also funded research infrastructure. The 100,000 Genomes Project uses data provided by patients and collected by the National Health Service as part of their care and support. We thank members of the ICGC/PCAWG working groups for generating the variant calls used in our case-control burden analyses. Peer Reviewed "Article signat per 38 autors/es: Robert Lesurf, Abdelrahman Said, Oyediran Akinrinade, Jeroen Breckpot, Kathleen Delfosse, Ting Liu, Roderick Yao, Gabrielle Persad, Fintan McKenna, Ramil R. Noche, Winona Oliveros, Kaia Mattioli, Shreya Shah, Anastasia Miron, Qian Yang, Guoliang Meng, Michelle Chan Seng Yue, Wilson W. L. Sung, Bhooma Thiruvahindrapuram, Jane Lougheed, Erwin Oechslin, Tapas Mondal, Lynn Bergin, John Smythe, Shashank Jayappa, Vinay J. Rao, Jayaprakash Shenthar, Perundurai S. Dhandapany, Christopher Semsarian, Robert G. Weintraub, Richard D. Bagnall, Jodie Ingles, Genomics England Research Consortium, Marta Melé, Philipp G. Maass, James Ellis, Stephen W. Scherer & Seema Mital"
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- 2022
20. Association of maternal socioeconomic status and race with risk of congenital heart disease: a population-based retrospective cohort study in Ontario, Canada
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Qun Miao, Sandra Dunn, Shi Wu Wen, Jane Lougheed, Cynthia Maxwell, Jessica Reszel, Kaamel Hafizi, and Mark Walker
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Heart Defects, Congenital ,Ontario ,Infant, Newborn ,Infant ,Mothers ,General Medicine ,Cohort Studies ,Social Class ,Pregnancy ,Humans ,Medicine ,Female ,Retrospective Studies - Abstract
ObjectiveTo investigate the interrelationships between maternal socioeconomic status (SES), race and congenital heart diseases (CHD) among infants.DesignRetrospective cohort study.Study settingOntario, Canada.Study populationAll singleton stillbirths and live births born in hospitals between 1 April 2012 and 31 March 2018 in Ontario, Canada (n=804 292).OutcomeCHD.AnalysisMultivariable logistic regression models were performed to assess associations between maternal neighbourhood household income, education level, race and CHD while adjusting for maternal age at birth, assisted reproductive technology, obesity, pre-existing health conditions, substance use during pregnancy, maternal rural residence and infant’s sex.ResultsCompared with infants whose mothers lived in the highest median household income neighbourhoods, infants whose mothers lived in the lowest median income neighbourhoods had a higher likelihood of having CHD (adjusted OR 1.15, 95% CI 1.06 to 1.24). Compared with infants whose mothers lived in neighbourhoods with more people with a university or higher degree, those infants whose mothers lived in neighbourhoods with less people with a university or higher degree had a higher chance of developing CHD (adjusted OR 1.26, 95% CI 1.16 to 1.36). Compared with white mothers, black mothers had a higher odds of giving birth to a child with CHD (adjusted OR 1.40, 95% CI 1.27 to 1.54). No association was detected between White and Asian mothers and CHD among infants.ConclusionsOur study indicates that there are inequities in CHD burden by maternal SES and race in Ontario, Canada. Further investigation is needed to examine racial variation in CHD using more detailed ethnic data.
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- 2022
21. Associations of congenital heart disease with deprivation index by rural-urban maternal residence: a population-based retrospective cohort study in Ontario, Canada
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Qun Miao, Sandra Dunn, Shi Wu Wen, Jane Lougheed, Fayza Sharif, and Mark Walker
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Heart Defects, Congenital ,Ontario ,Rural Population ,Information Systems and Management ,Urban Population ,Infant, Newborn ,Infant ,Health Informatics ,Cohort Studies ,Socioeconomic Factors ,Pregnancy ,Residence Characteristics ,Pediatrics, Perinatology and Child Health ,Humans ,Female ,Information Systems ,Demography ,Retrospective Studies - Abstract
Background The risk of congenital heart disease (CHD) has been found to vary by maternal socioeconomic status (SES) and rural-urban residence. In this study, we examined associations of CHD with two maternal SES indicators and stratified the analysis by maternal rural-urban residence. Methods This was a population-based retrospective cohort study. We included all singleton stillbirths and live hospital births from April 1, 2012 to March 31, 2018 in Ontario, Canada. We linked the BORN Information System and Canadian Institute for Health Information databases. Multivariable logistic regression models were used to examine associations of CHD with material deprivation index (MDI), social deprivation index (SDI), and maternal residence while adjusting for maternal age at birth, assisted reproductive technology, obesity, pre-pregnancy maternal health conditions, mental health illness before and during pregnancy, substance use during pregnancy, and infant’s sex. MDI and SDI were estimated at a dissemination area level in Ontario and were categorized into quintiles (Q1-Q5). Results This cohort study included 798,173 singletons. In maternal urban residence, the p trend (Cochran–Armitage test) was less than 0.0001 for both MDI and SDI; while for rural residence, it was 0.002 and 0.98, respectively. Infants living in the most materially deprived neighbourhoods (MDI Q5) had higher odds of CHD (aOR: 1.21, 95% CI: 1.12–1.29) compared to Q1. Similarly, infants living in the most socially deprived neighbourhoods (SDI Q5) had an 18% increase in the odds of CHD (aOR: 1.18, 95% CI: 1.1–1.26) compared to Q1. Rural infants had a 13% increase in the odds of CHD compared to their urban counterparts. After stratifying by maternal rural-urban residence, we still detected higher odds of CHD with two indices in urban residence but only MDI in rural residence. Conclusion Higher material and social deprivation and rural residence were associated with higher odds of CHD. Health interventions and policies should reinforce the need for optimal care for all families, particularly underprivileged families in both rural and urban regions. Future studies should further investigate the effect of social deprivation on the risk of CHD development.
- Published
- 2021
22. Age and Sex Differences in the Genetics of Cardiomyopathy
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Oyediran Akinrinade, Luis Altamirano-Diaz, John Smythe, Erwin Oechslin, Tapas Mondal, Jane Lougheed, and Seema Mital
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medicine.medical_specialty ,education.field_of_study ,Genetic heterogeneity ,TNNT2 ,business.industry ,Population ,Cardiomyopathy ,Late onset ,Odds ratio ,medicine.disease ,MYL3 ,Internal medicine ,Medicine ,MYH7 ,business ,education - Abstract
AimsCardiomyopathy is a clinically and genetically heterogeneous disorder with age and sex-related differences in severity and outcomes. The aim of our study was to identify age and sex-related differences in the genetic architecture of cardiomyopathy.Methods and ResultsWe analyzed whole genome sequence data from 471 pediatric and 926 adult cardiomyopathy patients from our Heart Centre Biobank and from the Genomics England cohort. Overall yield of rare deleterious coding variants was higher in pediatric compared to adult onset cardiomyopathy, but not different by sex.MYH7, TNNT2, MYL3, andVCLvariants were more frequent in pediatric patients;TTNandOBSCNvariants were more frequent in adult patients, withMYH7(Odds ratio 3.6; CI 2.1-6.3) andOBSCN(Odds ratio 5.5, CI 2.0-21.4) remaining significant after adjusting for multiple testing. Variants in early-onset cardiomyopathy clustered in highly constrained coding regions compared to those in adult patients (p=3.9×10−3). There were also differences between pediatric and adult patients in variant location withinMYH7andTTNgenes. When analyzed by sex, variants in female compared to male patients were in more highly constrained coding regions (p=0.002).ConclusionOur findings highlight under-appreciated genetic differences in early versus late onset cardiomyopathy. Variants in childhood cardiomyopathy and in female patients were in highly constrained coding regions of the genome suggesting greater deleterious effects and strong purifying selection in the general population. Knowledge of the affected gene, variant location within the gene, and variant constraint scores may be useful in predicting early versus late onset cardiomyopathy.
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- 2021
23. Characterization of physical literacy in children with chronic medical conditions compared with healthy controls: a cross-sectional study
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Brian M. Feldman, Jeffrey Do, Anna McCormick, Hugh J. McMillan, Denise De Laat, F. Virginia Wright, Sherri L. Katz, Sunita Venkateswaran, Patricia E. Longmuir, Johannes Roth, Robert J. Klaassen, Daniela Pohl, Leonardo R. Brandão, Erick Sell, Asif Doja, Jane Lougheed, Angelica Z. Blais, Donna L. Johnston, Katherine M. Matheson, Gail Macartney, and Addo Boafo
- Subjects
Gerontology ,Male ,Canada ,Health Knowledge, Attitudes, Practice ,Physiology ,Cross-sectional study ,Endocrinology, Diabetes and Metabolism ,Health Behavior ,MEDLINE ,Physical activity ,Physical literacy ,Physiology (medical) ,Medicine ,Humans ,Healthy Lifestyle ,Child ,Exercise ,Motivation ,Nutrition and Dietetics ,business.industry ,General Medicine ,Self Concept ,Cross-Sectional Studies ,Physical Fitness ,Case-Control Studies ,Chronic Disease ,Female ,business - Abstract
To determine the physical literacy, defined as the capability for a physically active lifestyle, of children with medical conditions compared with healthy peers, this multicenter cross-sectional study recruited children with medical conditions from cardiology, neurology (including concussion), rheumatology, mental health, respirology, oncology, hematology, and rehabilitation (including cerebral palsy) clinics. Participants aged 8–12 years (N = 130; mean age: 10.0 ± 1.44 years; 44% female) were randomly matched to 3 healthy peers from a normative database, based on age, gender, and month of testing. Total physical literacy was assessed by the Canadian Assessment of Physical Literacy, a validated assessment of physical literacy measuring physical competence, daily behaviour, knowledge/understanding, and motivation/confidence. Total physical literacy mean scores (/100) did not differ (t(498) = –0.67; p = 0.44) between participants (61.0 ± 14.2) and matched healthy peers (62.0 ± 10.7). Children with medical conditions had lower mean physical competence scores (/30; –6.5 [–7.44 to –5.51]; p < 0.001) but higher mean motivation/confidence scores (/30; 2.6 [1.67 to 3.63]; p < 0.001). Mean daily behaviour and knowledge/understanding scores did not differ from matches (/30; 1.8 [0.26 to 3.33]; p = 0.02;/10; –0.04 [–0.38 to 0.30]; p = 0.81; respectively). Children with medical conditions are motivated to be physically active but demonstrate impaired movement skills and fitness, suggesting the need for targeted interventions to improve their physical competence. Novelty: Physical literacy in children with diverse chronic medical conditions is similar to healthy peers. Children with medical conditions have lower physical competence than healthy peers, but higher motivation and confidence. Physical competence (motor skill, fitness) interventions, rather than motivation or education, are needed for these youth.
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- 2021
24. Abstract 14410: A Machine Learning Approach to Predicting Risk of Anthracycline Cardiotoxicity in Pediatric Cancer Survivors
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Jane Lougheed, Paul F. Kantor, Marie A. Chaix, Rejane Dillenburg, Myriam Lafreniere-Roula, Cedric Manlhiot, Leonard S. Sender, Stacey Marjerrison, Guoliang Meng, Roderick Yao, Ashok Kumar Manickaraj, Anne Christie, Seema Mital, Paul C. Nathan, Shayna Zelcer, Luc Mertens, Mylene Bassal, Neha Parmar, David R. W. Hodgson, James Ellis, Emily Lam, Peter Liu, Oyediran Akinrinade, Herschel Rosenberg, and Anastasia Miron
- Subjects
Oncology ,medicine.medical_specialty ,Cardiotoxicity ,Anthracycline ,business.industry ,Physiology (medical) ,Internal medicine ,medicine ,Cardio oncology ,Genetic risk ,Cardiology and Cardiovascular Medicine ,business ,Pediatric cancer - Abstract
Background: Despite known clinical and genetic risk factors, predicting anthracycline cardiotoxicity remains challenging. Objective: To develop a risk prediction model for anthracycline cardiotoxicity in childhood cancer survivors. Methods: We performed exome sequencing in 289 childhood cancer survivors at least 3 years from anthracycline exposure. In a nested case-control design, 183 cases with LV ejection fraction (LVEF) ≤55% despite low-dose doxorubicin (DOX) (≤250 mg/m2), and 106 controls with LVEF >55% despite DOX >250 mg/m2 were selected as extreme phenotypes. Rare/low-frequency variants were collapsed to identify genes differentially enriched for variants between cases and controls. The top-ranked genes were functionally evaluated in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and variant enrichment was confirmed in a replication cohort. Using random forest, a risk prediction model that included genetic and clinical predictors was developed. Results: Thirty-one genes were differentially enriched for variants between cases and controls (p-15 ] suggesting that absence of these variants may predispose to cardiotoxicity. A risk prediction model for cardiotoxicity that included clinical and genetic factors had a higher prediction accuracy and lower misclassification rate compared to the clinical model. In vitro inhibition of gene-associated pathways ( PI3KR2, ZNF827 ) provided protection from cardiotoxicity in CMs. Conclusions: Our study identified variants that protect against cardiotoxicity and informed the development of a prediction model for delayed anthracycline cardiotoxicity, and also provided new targets in autophagy genes for development of cardio-protective drugs.
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- 2020
25. Whole genome sequencing delineates regulatory and novel genic variants in childhood cardiomyopathy
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Kaia Mattioli, Lynn Bergin, Bhooma Thiruvahindrapuram, Wilson W L Sung, Anastasia Miron, Jane Lougheed, Ramil R. Noche, Philipp G. Maass, Tapas Mondal, Winona Oliveros, Oyediran Akinrinade, Fintan McKenna, Marta Melé, Stephen W. Scherer, Robert Lesurf, Seema Mital, Jeroen Breckpot, John Smythe, Qian Yang, Abdelrahman Said, Roderick Yao, Ting Liu, Michelle Chan Seng Yue, Erwin Oechslin, James Ellis, Guoliang Meng, and Kathleen Delfosse
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Whole genome sequencing ,Genetics ,DSC2 ,Genetic disorder ,Promoter ,Biology ,medicine.disease ,carbohydrates (lipids) ,chemistry.chemical_compound ,chemistry ,Gene expression ,medicine ,Enhancer ,Gene ,DNA - Abstract
Cardiomyopathy (CMP) is a heritable genetic disorder. Protein-coding variants account for 20-30% of cases. The contribution of variants in non-coding DNA elements that regulate gene expression has not been explored. We performed whole-genome sequencing (WGS) of 228 unrelated CMP families. Besides pathogenic protein-coding variants in known CMP genes, 5% cases harbored rare loss-of-function variants in novel cardiac genes, with NRAP and FHOD3 being strong candidates. WGS also revealed a high burden of high-risk variants in promoters and enhancers of CMP genes in an additional 20% cases (Odds ratio 2.14, 95% CI 1.60-2.86, p=5.26×10−7 vs 1326 controls) with genes involved in α-dystroglycan glycosylation (FKTN, DTNA) and desmosomal signaling (DSC2, DSG2) specifically enriched for regulatory variants (False discovery rate
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- 2020
26. Prevention of post-cardiac surgery vitamin D deficiency in children with congenital heart disease: a pilot feasibility dose evaluation randomized controlled trial
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Dean Fergusson, Ali Khamessan, Hope A. Weiler, Tara Girolamo, Glenville Jones, Pavel Geier, Katie O’Hearn, Stephanie Redpath, James Dayre McNally, Kusum Menon, Gyaandeo Maharajh, Lauralyn McIntyre, Jane Lougheed, Dermot R. Doherty, and Margaret L. Lawson
- Subjects
Vitamin ,Pediatrics ,medicine.medical_specialty ,Population ,Medicine (miscellaneous) ,Loading dose ,vitamin D deficiency ,High-dose ,law.invention ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Randomized controlled trial ,law ,medicine ,Vitamin D and neurology ,Pediatric intensive care unit ,030212 general & internal medicine ,Adverse effect ,education ,Congenital heart disease ,Cholecalciferol ,education.field_of_study ,lcsh:R5-920 ,Vitamin D deficiency ,business.industry ,Research ,030208 emergency & critical care medicine ,medicine.disease ,Clinical trial ,Critical care ,chemistry ,Dose evaluation trial ,business ,lcsh:Medicine (General) - Abstract
Background The vast majority of children undergoing cardiac surgery have low vitamin D levels post-operative, which may contribute to greater illness severity and worse clinical outcomes. Prior to the initiation of a large phase III clinical trial focused on clinical outcomes, studies are required to evaluate the feasibility of the study protocol, including whether the proposed dosing regimen can safely prevent post-operative vitamin D deficiency in this high-risk population. Methods We conducted a two-arm, double-blind dose evaluation randomized controlled trial in children requiring cardiopulmonary bypass for congenital heart disease. Pre-operatively, participants were randomized to receive cholecalciferol representing usual care (< 1 year = 400 IU/day, > 1 year = 600 IU/day) or a higher dose approximating the Institute of Medicine tolerable upper intake level (< 1 year = 1600 IU/day, > 1 year = 2400 IU/day). The feasibility outcomes were post-operative vitamin D status (primary), vitamin D-related adverse events, accrual rate, study withdrawal rate, blinding, and protocol non-adherence. Results Forty-six children were randomized, and five withdrew prior to surgery, leaving 41 children (21 high dose, 20 usual care) in the final analysis. The high dose group had higher 25-hydroxyvitamin D concentrations both intraoperatively (mean difference + 25.9 nmol/L; 95% CI 8.3–43.5) and post-operatively (mean difference + 17.2 nmol/L; 95% CI 5.5–29.0). Fewer participants receiving high-dose supplementation had post-operative serum 25-hydroxyvitamin D concentrations under 50 nmol/L, compared with usual care (RR 0.31, 95% CI 0.11–0.87). Post-operative vitamin D status was associated with the treatment arm and the number of doses received. There were no cases of hypercalcemia, and no significant adverse events related to vitamin D. While only 75% of the target sample size was recruited (limited funding), the consent rate (83%), accrual rate (1.5 per site month), number of withdrawals (11%), and ability to maintain blinding support feasibility of a larger trial. Conclusions Pre-operative daily high-dose supplementation improved vitamin D status pre-operatively and at time of pediatric ICU admission. The protocol for a more definitive trial should limit enrollment of children with at least 30 days between randomization and surgery to allow adequate duration of supplementation or consider a loading dose. Trial registration ClinicalTrials.gov, NCT01838447. Registered on April 24, 2013
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- 2020
27. Return of genetic and genomic research findings: Experience of a pediatric biorepository
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Oyediran Akinrinade, Eriskay Liston, Seema Mital, Dimitri J. Stavropoulos, Raymond H. Kim, Jeroen Breckpot, Rebekah Jobling, Anastasia Miron, Laura Zahavich, Jane Lougheed, Lynn Bergin, Erwin Oechslin, Tapas Mondal, Tanya Papaz, Luis Altamirano-Diaz, John Smythe, Miriam S. Reuter, and Roderick Yao
- Subjects
0301 basic medicine ,lcsh:Internal medicine ,medicine.medical_specialty ,lcsh:QH426-470 ,Referral ,Databases, Factual ,Genomic research ,Genetic counseling ,Return of research findings ,Primary findings ,030105 genetics & heredity ,Genome sequencing ,Pediatrics ,03 medical and health sciences ,Genetics ,medicine ,Humans ,lcsh:RC31-1245 ,Genetics (clinical) ,Receipt ,business.industry ,Genomics ,Cost of return ,Biobank ,Human genetics ,lcsh:Genetics ,030104 developmental biology ,Biorepository ,Family medicine ,Costs and Cost Analysis ,Navigating return ,Medical genetics ,business ,Research Article - Abstract
BackgroundAssess process, uptake, validity and resource needs for return of actionable research findings to biobank participants.MethodsParticipants were prospectively enrolled in a multicenter biorepository of childhood onset heart disease. Clinically actionable research findings were reviewed by a Return of Research Results Committee (RRR) and returned to the physician or disclosed directly to the participant through a research genetic counselor. Action taken following receipt of this information was reviewed.ResultsGenetic data was generated in 1963 of 7408 participants. Fifty-nine new findings were presented to the RRR committee; 20 (34%) were deemed reportable. Twelve were returned to the physician, of which 7 were disclosed to participants (median time to disclosure, 192 days). Seven findings were returned to the research genetic counselor; all have been disclosed (median time to disclosure, 19 days). Twelve families (86%) opted for referral to clinical genetics after disclosure of findings; 7 results have been validated, 5 results are pending. Average cost of return and disclosure per reportable finding incurred by the research program was $750 when utilizing a research genetic counselor; clinical costs associated with return were not included.ConclusionsReturn of actionable research findings was faster if disclosed directly to the participant by a research genetic counselor. There was a high acceptability amongst participants for receiving the findings, for referral to clinical genetics, and for clinical validation of research findings, with all referred cases being clinically confirmed.
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- 2019
28. Impacting child health outcomes in congenital heart disease: Cluster randomized controlled trial protocol of in-clinic physical activity counselling
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Kambiz Norozi, Jane Lougheed, Andrew R. Willan, Olivia Lemire, Jenna Yaraskavitch, Jennifer Graham, Andrew S. Mackie, and Patricia E. Longmuir
- Subjects
Counseling ,Heart Defects, Congenital ,Male ,medicine.medical_specialty ,Canada ,Randomization ,Adolescent ,Cardiac Care Facilities ,Pediatrics ,Pragmatic trial ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Quality of life (healthcare) ,Randomized controlled trial ,law ,Intervention (counseling) ,Health care ,medicine ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Child ,Exercise ,Motivation ,030505 public health ,business.industry ,Repeated measures design ,General Medicine ,Actigraphy ,3. Good health ,Innocent heart murmur ,Health promotion ,Research Design ,Child, Preschool ,Pedometer ,Physical therapy ,Quality of Life ,Female ,0305 other medical science ,business - Abstract
Background Most (>90%) children with congenital health defects are not active enough for optimal health. Proactively promoting physical activity during every clinic visit is recommended, but rarely implemented due to a lack of appropriate resources. Methods This cluster randomized controlled trial will implement an evidence-based, multi-faceted physical activity intervention. All eligible patients at small (London, ON), medium (Ottawa, ON) and large (Edmonton, AB) pediatric cardiac clinics will be approached, with randomization to intervention/control by clinic and week. Intervention patients will be counselled with 5 key physical activity messages, have questions about physical activity answered, and have access to a custom web site with personalized activity suggestions and support from a Registered Kinesiologist. The primary outcome is daily physical activity (number of steps, minutes of moderate-to-vigorous activity) assessed via pedometer one week per month for 6-months. Standardized questionnaires assess activity motivation and quality of life at baseline and end of study. Healthcare outcomes will be clinic visit time and contacts for physical activity concerns. Repeated measures ANCOVA will compare control/intervention pedometer outcomes, adjusting for covariates (alpha=0.05). Conclusions This trial aims to determine whether providing resources and protocols enables clinicians to counsel about physical activity as part of every pediatric cardiology appointment. Evaluations of healthcare system impact and intervention delivery in small, medium and large clinics will assess applicability for implementation in all pediatric cardiac clinics. The impact on physical activity motivation and participation will evaluate the effectiveness of this standardized approach for increasing physical activity in children with congenital heart defects.
- Published
- 2019
29. 'I really like playing games together': Understanding what influences children with congenital heart disease to participate in physical activity
- Author
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Jenna Yaraskavitch, Patricia E. Longmuir, Jane Lougheed, Kristi B. Adamo, and Angelica Z. Blais
- Subjects
Heart Defects, Congenital ,Male ,Heart disease ,media_common.quotation_subject ,Physical activity ,Context (language use) ,Social Inclusion ,Peer Group ,Developmental psychology ,03 medical and health sciences ,0302 clinical medicine ,030225 pediatrics ,Perception ,Developmental and Educational Psychology ,medicine ,Intrinsic motivation ,Humans ,0501 psychology and cognitive sciences ,Complex congenital heart disease ,Child ,Exercise ,media_common ,Ontario ,Motivation ,05 social sciences ,Public Health, Environmental and Occupational Health ,Focus Groups ,medicine.disease ,Focus group ,Self Efficacy ,Play and Playthings ,Feeling ,Pediatrics, Perinatology and Child Health ,Female ,Family Relations ,Psychology ,050104 developmental & child psychology ,Sports - Abstract
Background Participation in physical activity is essential to the long-term health and development of all children. However, children living with cardiac conditions are typically not active enough to sustain positive health outcomes. Understanding the experiences of children living with congenital heart disease in community-based settings could help inform the physical activity counselling practices of clinicians. The current study explored the perceptions of 7- to 10-year-old children with moderate or complex congenital heart disease as they participated in a 10-week multisport programme. Methods Detailed field notes recorded the discussions and behaviours of 11 participants (45% female participants) each week during the programme sessions. Among those, four participants (50% female participants) were purposively selected to participate in preprogramme and postprogramme focus groups to gather more detailed accounts of their experiences. Results Four main themes surrounding physical activity were identified: (a) motivation, (b) self-efficacy, (c) peer influences, and (d) family influences. Although feelings of excitement and enjoyment towards physical activity were prevalent throughout the data ("I'm really excited … because I really like those sports"), participants also often felt frustrated, nervous, and fatigued ("I'm not very good at the skills"). Social inclusion with peers and family influences were meaningful reasons to engage in physical activity ("I really like playing games together"). Following the completion of the programme, participants emphasized their enjoyment of physical activity as a primary source of motivation, demonstrating an important shift from recognizing positive health outcomes ( "… it's good for you") towards more intrinsic sources of motivation ("… because it's fun"). Conclusion Opportunities for physical activity that enhance positive experiences and build intrinsic motivation should be identified and promoted to children with congenital heart disease. Community-based programmes may also be an appropriate context for children with cardiac conditions to engage and maintain participation in physical activity through adolescence.
- Published
- 2019
30. Sensitivity, specificity, and reliability of the Get Active Questionnaire for identifying children with medically necessary special considerations for physical activity
- Author
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Hugh J. McMillan, Lillian Lai, Karen Watanabe Duffy, Johannes Roth, Suzie Lee, Maala Bhatt, Daniela Pohl, Carol Theoret-Douglas, Letizia Gardin, Christine Lamontagne, Emily Ertel, Patricia E. Longmuir, Sherri L. Katz, Derek Wong, Roman Jurencak, Anna McCormick, Roger Zemek, Ciarán M. Duffy, Julia Jackson, Asif Doja, and Jane Lougheed
- Subjects
Male ,Adolescent ,Physiology ,Computer science ,Endocrinology, Diabetes and Metabolism ,Physical activity ,Cardiology ,030209 endocrinology & metabolism ,Sensitivity and Specificity ,Medical Records ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Physiology (medical) ,Physicians ,Surveys and Questionnaires ,Humans ,Sensitivity (control systems) ,Child ,Exercise ,False Negative Reactions ,Reliability (statistics) ,Nutrition and Dietetics ,Reproducibility of Results ,030229 sport sciences ,General Medicine ,Reliability engineering ,Child, Preschool ,Female - Abstract
Physical activity is promoted for optimal health but may carry risks for children who require medically necessary activity restrictions. The sensitivity, specificity, and reliability of the Get Active Questionnaire (GAQ) for identifying children needing special considerations during physical activity was evaluated among parents of 207 children aged 3 to 14 years (97 (47%) female, mean age of 8.4 ± 3.7 years). GAQ responses were compared with reports obtained directly from the treating physician (n = 192/207) and information in the medical chart (clinic notes/physician letter, n = 111/207). Parent GAQ responses (either “No to all questions” or “Yes to 1 or more questions”) agreed with physician (κ = 0.16, p = 0.003) and medical record (κ = 0.15, p = 0.003) reports regarding the need for special consideration during physical activity (Yes/No). Sensitivity was 71% (20/28) and specificity was 59% (96/164), with few false-negative responses. The GAQ was most effective for rheumatology and cardiology patients. False positives were 29% to 46%, except among chronic pain (80%) and rehabilitation (75%) patients. Test–retest reliability was moderate (Cronbach’s α = 0.70) among 57 parents who repeated the GAQ 1 week later. The GAQ effectively identified children not requiring physical activity restrictions and those with medical conditions similar to those of concern among adults. Additional questions from a qualified exercise professional, as recommended for a “Yes” response on the GAQ, should reduce the false-positive burden. Indicating the timeframe of reference for each question and including an option to describe other special considerations (e.g., medication, supervision) are recommended.
- Published
- 2018
31. Participation in a Community-Based Sport Program is Feasible for Children with Congenital Heart Disease and May Benefit Physical Literacy Development: A Pilot Study
- Author
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Jane Lougheed, Angelica Z. Blais, Kristi B. Adamo, and Patricia E. Longmuir
- Subjects
Community based ,Gerontology ,movement skill ,Heart disease ,business.industry ,Physical activity ,physical activity ,medicine.disease ,developmental delay ,muscular endurance ,Physical literacy ,motor development ,Medicine ,lcsh:Sports medicine ,lcsh:RC1200-1245 ,business ,Motor skill - Abstract
Objectives: Children with congenital heart disease (CHD) often lack confidence and demonstrate limited movement skills during physical activity. Community-based sport programs have been suggested to build their confidence and competence. This study examined the feasibility and physical literacy impact of an existing community-based sport program for children with moderate to complex CHD. Methods: This pilot study employed a parallel mixed method, single-case experimental design to evaluate the feasibility and impact of a weekly, community-based sport intervention (Sportball©). Intervention field notes and focus group transcripts were analysed deductively to inform feasibility. Physical literacy outcomes were measured using the Canadian Assessment of Physical Literacy. Paired t-tests examined changes in physical literacy scores, while qualitative data informed perceived changes in physical literacy tasks. Results: Participants (n=11, 45% female) were 8.2 ± 1.2 years. Nine children completed >80% of the 1-hour Sportball© sessions (10 lessons total). No adverse events occurred during or as a result of the intervention. Enabling participants to recognize the sensations of exercise and whether or not they needed to rest, designing activities and instructions to mitigate the risk of body contact, and accommodating the needs of participants with developmental/attentional limitations were important factors embedded into the design of the program, contributing to its feasibility. Participants reported perceived improvements in movement skill and torso endurance/strength, changes which were reflected in the objective physical literacy measures (movement skill: ∆ mean= 2.0 ± 0.98 points, p=0.07, r=0.57; torso endurance/strength: ∆ mean= 5.27 ± 7.20 seconds, p=0.44, r=0.26). Conclusions: The Sportball© intervention was feasible for children with CHD, including those with activity restrictions or developmental delays. Children enjoyed the program and wanted it to continue. Measurable improvements in movement skill and muscular endurance were recognized by participants. Future trials evaluating Sportball©’s impact with larger samples and multiple 10-week sessions are recommended.
- Published
- 2020
32. Associations of Assisted Reproductive Technology and Twin Pregnancy With Risk of Congenital Heart Defects
- Author
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Daniel J. Corsi, Andrea Lanes, Michael J. Davies, Monica Taljaard, Laura Gaudet, Jane Lougheed, Qun Miao, A. Leader, Ann E. Sprague, Mark Walker, and Shi Wu Wen
- Subjects
Adult ,Heart Defects, Congenital ,medicine.medical_specialty ,Reproductive Techniques, Assisted ,medicine.medical_treatment ,Intracytoplasmic sperm injection ,Pregnancy ,Risk Factors ,Prevalence ,Humans ,Medicine ,Twin Pregnancy ,Retrospective Studies ,Ontario ,Assisted reproductive technology ,In vitro fertilisation ,business.industry ,Obstetrics ,Retrospective cohort study ,Odds ratio ,medicine.disease ,Relative risk ,Pediatrics, Perinatology and Child Health ,Pregnancy, Twin ,Female ,business - Abstract
Importance The extent to which assisted reproductive technology is associated with increased risk of congenital heart defects independent of its known association with twinning remains uncertain. Objective To assess the extent to which assisted pregnancy is associated with increased risk of congenital heart defects independent of its known association with twinning. Design, setting, and participants This retrospective cohort study linked records of congenital heart defect diagnoses with assisted reproductive technology cycles in 507 390 singleton or twin pregnancies (10 149 assisted pregnancies and 497 241 nonassisted pregnancies), including singleton and twin early pregnancy losses, stillbirths, and live births (follow-up to 1 year of age) in Ontario, Canada, between April 1, 2012, and October 31, 2015. Statistical analysis was performed from January 1, 2017, to September 9, 2019. Exposures Assisted reproductive technology and its 2 subtypes: intracytoplasmic sperm injection and in vitro fertilization without intracytoplasmic sperm injection. Main outcomes and measures The main outcome was congenital heart defects (prevalence and relative risk measured as odds ratios [ORs]). Mediation analysis was performed to assess the extent to which the association between assisted reproductive technology and congenital heart defects was mediated by twinning. Results Of 507 390 mother-infant pairs with singleton or twin pregnancies evaluated, the prevalence of congenital heart defects in assisted pregnancies (223 [2.2%]) was higher than that in nonassisted pregnancies (6057 [1.2%]; crude OR, 1.82; 95% CI, 1.59-2.09). The strength of the association between assisted pregnancy and congenital heart defects decreased after adjusting for several risk factors simultaneously (adjusted OR, 1.70; 95% CI, 1.48-1.95). Further mediation analysis indicated that most of the association between assisted pregnancy and congenital heart defects was mediated by twinning (adjusted OR, 1.68; 95% CI, 1.44-1.92), and the natural direct association of assisted pregnancy with congenital heart defects among singleton pregnancies was 1.09 (95% CI, 0.93-1.25). Mediation of twinning accounted for 87.3% of the association. Conclusions and relevance Our study results suggest that the association between assisted reproductive technology and congenital heart defects may be mediated by twinning.
- Published
- 2020
33. Update in Pediatric Cardiology
- Author
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Jenna Ashkanase and Jane Lougheed
- Subjects
medicine.medical_specialty ,medicine.diagnostic_test ,Heart disease ,business.industry ,medicine.medical_treatment ,Hypertrophic cardiomyopathy ,Prenatal diagnosis ,Dilated cardiomyopathy ,Chest pain ,medicine.disease ,Cardiac surgery ,medicine ,medicine.symptom ,Intensive care medicine ,business ,Genetic testing ,Cardiac catheterization - Abstract
The field of pediatric cardiology has changed significantly over the past decade. The epidemiology of congenital heart disease (CHD) is shifting, with increased prenatal diagnosis, improved survival, and improved imaging and intervention techniques. Long term issues including neurodevelopmental outcome, exercise capacity, quality of life and reproduction have become more important as children survive their heart disease into adulthood. Neonatal oximetry screening is becoming routine practice to ensure that the majority of critical CHD is diagnosed as early as possible, as this has a positive impact on outcome. Imaging techniques in pediatric cardiology are evolving rapidly. Echocardiography remains the mainstay of imaging, with new techniques of 3D imaging and advanced function assessment adding to its utility. Cardiac MRI and CT are becoming important adjunct imaging techniques, particularly due the 3D and spatial information obtained. Cardiac catheterization with angiography is utilized less as a solely diagnostic technique, but has a substantial and increasing role in non-surgical intervention for CHD. Genetic testing in pediatric cardiology is adding yet further information regarding diagnosis, treatment options and prognosis in CHD, cardiomyopathies and cardiac channelopathies.
- Published
- 2018
34. Weight Trajectories Are Associated With Exercise Capacity Among Children With Complex Congenital Heart Defects
- Author
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Tyler Kung, Jane Lougheed, Patricia E. Longmuir, Warsame Yusuf, and Kenneth Tang
- Subjects
medicine.medical_specialty ,Physical medicine and rehabilitation ,business.industry ,medicine ,Physical Therapy, Sports Therapy and Rehabilitation ,Orthopedics and Sports Medicine ,Exercise capacity ,business - Published
- 2019
35. GENOMIC ARCHITECTURE OF TETRALOGY OF FALLOT AND GENOMIC PREDICTORS OF ADVERSE RIGHT VENTRICULAR REMODELLING
- Author
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Bhooma Thiruvahindrapuram, L. Altamirano Diaz, R. Yao, Stephen W. Scherer, M. Chaix, Elaine Gordon, Myriam Lafreniere-Roula, Seema Mital, Erwin Oechslin, Tapas Mondal, G.S. Van Arsdell, G. Tran, John Smythe, Jane Lougheed, W. Sung, Lynn Bergin, R. Van der Laan, C. Bezzina, Cedric Manlhiot, and Oyediran Akinrinade
- Subjects
medicine.medical_specialty ,business.industry ,Internal medicine ,Genomic architecture ,medicine ,Cardiology ,Cardiology and Cardiovascular Medicine ,business ,medicine.disease ,Tetralogy of Fallot - Published
- 2018
36. Factors Influencing Participation in a Population-based Biorepository for Childhood Heart Disease
- Author
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Carly Ogaki, Elaine Gordon, Herschel Rosenberg, David Chitayat, Lynn Bergin, Christine Dodge, Erwin Oechslin, Seema Mital, Mina Safi, Tanya Papaz, Jennifer Breaton Kyryliuk, Catherine Chant-Gambacort, Liz Burrill, Jane Lougheed, Tapas Mondal, Laura-Lee Walter, Ashok Kumar Manickaraj, and John Smythe
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Heart Diseases ,Population ,Young Adult ,Age Distribution ,medicine ,Humans ,Prospective Studies ,Young adult ,Patient participation ,Child ,Psychiatry ,Prospective cohort study ,education ,Aged ,Biological Specimen Banks ,Aged, 80 and over ,education.field_of_study ,business.industry ,Medical record ,Infant ,Middle Aged ,Biobank ,humanities ,Biorepository ,Child, Preschool ,Donation ,Family medicine ,Pediatrics, Perinatology and Child Health ,Female ,Patient Participation ,business - Abstract
BACKGROUND: Consenting minors for genetics research and biobanking involves ethical and social challenges. We examined factors influencing participation rates in a population-based biorepository for childhood heart disease. METHODS: Individuals were prospectively enrolled across 7 centers in Ontario by using a standardized consent form. Individuals were approached for consent for the donation of blood/saliva (DNA), tissue, and skin from the affected individual for future genomics and stem cell research. Consent rates were compared between pediatric and adult patients and factors affecting consent were analyzed by using multiple logistic regression analysis. RESULTS: From 2008 to 2011, 3637 patients were approached. A total of 2717 pediatric patients consented (90% consent rate); mean age was 8.5 ± 5.8 years (57% male; 76% white). A total of 561 adult patients consented (92% consent rate, P = .071 versus pediatric). Factors associated with lower pediatric consent rates included younger age, race, absence of complex defects, and location of consent; these were not associated with adult consent rates. Leading causes for refusal of consent were lack of interest in research (43%), overwhelmed clinically (14%), and discomfort with genetics (11%). Concerns related to privacy, insurability, indefinite storage, and ongoing access to medical records were not the leading causes for refusal. CONCLUSIONS: The high pediatric consent rate (90%) was comparable with that of adults. Ethical, social, or legal issues were not the leading reasons for refusal of consent.
- Published
- 2012
37. Genetic determinants of right-ventricular remodeling after tetralogy of Fallot repair
- Author
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Caroline Kinnear, Andrew N. Redington, Seema Mital, John Smythe, Aamir Jeewa, Tapas Mondal, Jane Lougheed, Herschel Rosenberg, Cedric Manlhiot, Brian W. McCrindle, Ashok Kumar Manickaraj, Luc Mertens, and Glen S. Van Arsdell
- Subjects
Reoperation ,medicine.medical_specialty ,Pathology ,Time Factors ,Genotype ,Heart Ventricles ,Ventricular Dysfunction, Right ,Pulmonary insufficiency ,Hemodynamics ,Kaplan-Meier Estimate ,Biology ,Polymorphism, Single Nucleotide ,Article ,Transforming Growth Factor beta1 ,Gene Frequency ,Fibrosis ,Internal medicine ,medicine ,Humans ,Prospective Studies ,Registries ,Angiogenic Proteins ,Cardiac Surgical Procedures ,Hypoxia ,Ventricular remodeling ,Tetralogy of Fallot ,Hypertrophy, Right Ventricular ,Ventricular Remodeling ,Infant ,Hypoxia-Inducible Factor 1, alpha Subunit ,medicine.disease ,Adaptation, Physiological ,Logistic Models ,Phenotype ,Treatment Outcome ,HIF1A ,medicine.anatomical_structure ,Child, Preschool ,Pulmonary valve ,Pediatrics, Perinatology and Child Health ,Linear Models ,Cardiology ,Follow-Up Studies - Abstract
Background: hypoxia-inducible factor (HIF1A) regulates the myocardial response to hypoxia and hemodynamic load. We investigated the association of variants with right-ventricular (RV) remodeling after tetralogy of Fallot (TOF) repair. Methods: children with TOF were genotyped for three single-nucleotide polymorphisms in HIF1A. Genotypes were analyzed for association with RV myocardial protein expression and fibrosis at complete repair (n = 42) and RV dilation, fractional area change, and freedom from pulmonary valve/conduit replacement on follow-up. results: In 180 TOF patients, mean age at repair was 1.0 ± 0.8 y with follow-up at 9.0 ± 3.5 y; 82% had moderate to severe pulmonary insufficiency. Freedom from RV reinterventions at 5, 10, and 15 y was 92, 84, and 67%, respectively. Patients with more functioning HIF1A alleles had higher transforming growth factor β1 expression and more fibrosis at initial repair as compared with controls (P < 0.05). During follow-up, patients with more functioning HIF1A alleles showed less RV dilation, better preservation of RV function, and greater freedom from RV reinterventions (P < 0.05). This was confirmed in a replication cohort of 69 patients. conclusion: In children who have had TOF repair, a lower number of functioning HIF1A alleles was associated with RV dilation and dysfunction, suggesting that hypoxia adaptation in unrepaired TOF may influence RV phenotype after repair.
- Published
- 2012
38. L'évaluation du risque cardiaque avant l'utilisation de stimulants chez les enfants et les adolescents
- Author
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Jacques LeBlanc, Martin S, Shubhayan Sanatani, J-M Côté, Andrew E. Warren, Gorman Da, Robert M. Hamilton, M Weiss, Clare Gray, C Mitchell, Robert M. Gow, Stacey Ageranioti Bélanger, B Miles, Russell Schachar, and Jane Lougheed
- Subjects
business.industry ,Pediatrics, Perinatology and Child Health ,Medicine ,business ,Sudden death ,Humanities - Abstract
Il est demontre que le traitement pharmacologique par des stimulants reduit les symptomes associes au trouble de deficit de l’attention avec hyperactivite (TDAH), et ce traitement fait partie des recommandations therapeutiques de l’American Academy of Pediatrics pour les enfants presentant ce trouble (1,2). Cependant, de recentes decisions en matiere de reglementation sur l’homologation et l’etiquetage des medicaments contre le TDAH (3,4), ainsi qu’un recent document de principes de l’American Heart Association (5), une correction et une reponse (clarification) de l’American Academy of Pediatrics (6,7), ont souleve des questions sur l’evaluation et la therapie du TDAH que preconisent les praticiens canadiens. La pratique canadienne actuelle dans le domaine de la pharmacotherapie du TDAH et du depistage cardiovasculaire est mixte, et il y a peu de consensus quant a l’evaluation pertinente des enfants avant d’instaurer la pharmacotherapie du TDAH (8). Les avis sont encore plus partages au sujet de l’innocuite du traitement des enfants ayant subi une refection ou une palliation de leur cardiopathie congenitale (CPC) et qui prennent des medicaments contre le TDAH (8). Afin d’orienter les medecins canadiens qui soignent les enfants ayant un TDAH et de clarifier la situation, la Societe canadienne de pediatrie, la Societe canadienne de cardiologie et l’Academie canadienne de psychiatrie de l’enfant et de l’adolescent ont prepare conjointement le present document de principes. Il contient des recommandations consensuelles sur l’evaluation du risque cardiaque chez les enfants ayant un TDAH a qui on envisage d’administrer des stimulants. Il ne s’attarde pas au diagnostic de TDAH, ni aux bienfaits therapeutiques des stimulants. De meme, il n’aborde pas le bien-fonde ou les risques relatifs d’un medicament par rapport a un autre au sein de cette population de patients. Enfin, les medicaments non stimulants utilises dans le traitement du TDAH, y compris l’atomoxetine, les antidepresseurs et les agonistes alpha-adrenergiques, ne font pas l’objet d’une analyse particuliere.
- Published
- 2009
39. The Measurement of the QT and QTc on the Neonatal and Infant Electrocardiogram: A Comprehensive Reliability Assessment
- Author
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Robert M. Gow, Letizia Gardin, Benjamin Ewald, Lillian Lai, and Jane Lougheed
- Subjects
Male ,medicine.medical_specialty ,Intraclass correlation ,Long QT syndrome ,Sudden death ,QT interval ,Electrocardiography ,Heart Rate ,Physiology (medical) ,Internal medicine ,Statistics ,medicine ,Humans ,Reliability (statistics) ,Observer Variation ,Reproducibility ,business.industry ,Infant, Newborn ,Infant ,Reproducibility of Results ,Original Articles ,General Medicine ,Repeatability ,medicine.disease ,Long QT Syndrome ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business ,Kappa - Abstract
Background: An electrocardiogram has been proposed to screen for prolonged QT interval that may predispose infants to sudden death in the first year of life. Understanding the reliability of QT interval measurement will inform the design of a screening program. Methods: Three pediatric cardiologists measured the QT/RR intervals on 60 infant electrocardiograms (median age 46 days), from leads II, V5 and V6 on three separate occasions, 7 days apart, according to a standard protocol. The QTc was corrected by Bazett's (QTcB), Fridericia's (QTCFrid), and Hodges' (QTcH) formulae. Intraobserver and interobserver reliability were assessed by intraclass correlation coefficients (ICC), limits of agreement and repeatability coefficients for single, average of two and average of three measures. Agreement for QTc prolongation (> 440 msec) was assessed by kappa coefficients. Results: QT interval intraobserver ICC was 0.86 and repeatability coefficient was 25.9 msec; interobserver ICC increased from 0.88 for single observations to 0.94 for the average of 3 measurements and repeatability coefficients decreased from 22.5 to 16.7 msec. For QTcB, intraobserver ICC was 0.67, and repeatability was 39.6 msec. Best interobserver reliability for QTcB was for the average of three measurements (ICC 0.83, reproducibility coefficient 25.8 msec), with further improvement for QTcH (ICC 0.92, reproducibility coefficient 16.69 msec). Maximum interobserver kappa for prolonged QTc was 0.77. Misclassification around specific cut points occurs because of the repeatability coefficients. Conclusions: Uncorrected QT measures are more reliable than QTcB and QTCFrid. An average of three independent measures provides the most reliable QT and QTc measurements, with QTcH better than QTcB.
- Published
- 2009
40. Effects of Repeated Courses of Antenatal Corticosteroids on Somatic Development in Children 6 to 10 Years of Age
- Author
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William Gibb, Robin C Walker, Mark Walker, Xi-Kuan Chen, Shi Wu Wen, Margaret L. Lawson, and Jane Lougheed
- Subjects
Adult ,Pediatrics ,medicine.medical_specialty ,Percentile ,Hydrocortisone ,Cephalometry ,medicine.drug_class ,Body Mass Index ,Cohort Studies ,Adrenal Cortex Hormones ,Pregnancy ,Heart rate ,medicine ,Humans ,Child ,Saliva ,Decreased head circumference ,Retrospective Studies ,Morning ,business.industry ,Obstetrics and Gynecology ,Retrospective cohort study ,Blood pressure ,Case-Control Studies ,Prenatal Exposure Delayed Effects ,Pediatrics, Perinatology and Child Health ,Corticosteroid ,Female ,business ,Body mass index - Abstract
This study assessed the effects of repeated courses of antenatal corticosteroids on biometric characteristics, salivary cortisol, and heart function in children 6 to 10 years of age using a retrospective cohort study. Twenty-nine children whose mothers had received two or more courses of antenatal corticosteroids were identified from hospital charts. Eighty-seven children whose mothers did not receive antenatal corticosteroids were frequency matched with the exposed group by child's age, sex, and ethnicity. The body development, heart function, and salivary corticosteroid level were evaluated at 6 to 10 years of age. The percentiles of body measurements were calculated based on the 2000 Centers for Disease Control and Prevention growth charts. The general linear models were applied to assess the observed association. Decreased head circumference ( P = 0.017) and body mass index (BMI) ( P = 0.047) in children 6 to 10 years of age were associated with repeated courses of antenatal corticosteroids. Morning salivary cortisol level was lower in the exposed group than the unexposed group ( P = 0.048). No difference was found in height, weight, blood pressure, heart rate, and echocardiogram measurements between the two groups. Repeated courses of antenatal corticosteroid therapy are associated with decreased head circumference, BMI, and salivary cortisol level in children 6 to 10 years of age.
- Published
- 2008
41. Spectrum of Cardiovascular Disease, Accuracy of Diagnosis, and Outcome in Fetal Heterotaxy Syndrome
- Author
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Jane Lougheed, Joyce S.L. Lim, Lisa K. Hornberger, Shi-Joon Yoo, and Mio Taketazu
- Subjects
Heart Defects, Congenital ,medicine.medical_specialty ,Pediatrics ,Vena Cava, Superior ,Heart block ,Gestational Age ,Vena Cava, Inferior ,Ultrasonography, Prenatal ,Intracardiac injection ,Fetal Heart ,Pregnancy ,Internal medicine ,Humans ,Medicine ,Abnormalities, Multiple ,Heart Atria ,cardiovascular diseases ,Survival analysis ,Fetus ,business.industry ,Pregnancy Outcome ,Gestational age ,Syndrome ,medicine.disease ,Survival Analysis ,Fetal Diseases ,Echocardiography ,Pulmonary Veins ,In utero ,Circulatory system ,cardiovascular system ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies - Abstract
Because there is a paucity of information regarding the diagnosis and outcomes of fetal heterotaxy syndrome (HS), this study sought to determine the spectrum of cardiac pathology, accuracy of diagnosis, and outcome of fetal HS. All cases of fetal HS encountered in the investigators' institution over a 10-year period through 2002 were identified. Prenatal and postnatal echocardiograms and medical records were reviewed. Seventy-one fetuses were diagnosed with HS, including 48 with left atrial isomerism (LAI) and 23 with right atrial isomerism (RAI). For LAI and RAI, most intracardiac lesions, the pulmonary venous connections, and superior vena caval anatomy were correctly diagnosed in utero (93%, 86%, and 77% accuracy, respectively), whereas hepatic venous connections and inferior vena caval-atrial connections in RAI were difficult to define (65% and 56% accuracy, respectively). Of 32 continued and followed pregnancies with LAI, 22 are currently alive at 48 +/- 30 months. Heart block and associated major extracardiac pathology were significantly more common in nonsurvivors with fetal LAI (p = 0.007 and 0.024, respectively). Outcomes were even worse for prenatally diagnosed RAI: of 14 continued pregnancies, only 3 are currently alive. In conclusion, fetal HS is associated with a broad spectrum of cardiac pathology, which can be diagnosed accurately in utero. Fetal LAI is associated with a mortality of 31%, with heart block and extracardiac pathology as primary risk factors for perinatal mortality. The outcome of prenatally diagnosed RAI is poor.
- Published
- 2006
42. WITHDRAWN: Presentation, Diagnosis, and Medical Management of Heart Failure in Children: Canadian Cardiovascular Society Guidelines
- Author
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Aamir Jeewa, Reeni Soni, Derek G. Human, Kenny K. Wong, Paul F. Kantor, Michael McGillion, Lindsay M. Ryerson, Steven C. Greenway, Jane Lougheed, Kristen George, Carol Chan, Adrian Dancea, J. Conway, S. Lucy Roche, Holger Buchholz, Nicole Barbosa, Joseph Atallah, Robert D. Ross, Jack F. Price, Catherine Chant-Gambacort, Letizia Gardin, Rejane Dillenburg, and Judith Wilson
- Subjects
medicine.medical_specialty ,Presentation ,business.industry ,media_common.quotation_subject ,Pediatrics, Perinatology and Child Health ,Management of heart failure ,Alternative medicine ,Medicine ,Canadian Cardiovascular Society ,business ,Intensive care medicine ,media_common - Published
- 2014
43. Acquired right ventricular outflow tract obstruction in the recipient twin in twin-twin transfusion syndrome
- Author
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Jean-Luc Bigras, Greg Ryan, Karen Fung Kee Fung, Brian Sinclair, Jane Lougheed, Jeffrey F. Smallhorn, and Lisa K. Hornberger
- Subjects
Canada ,medicine.medical_specialty ,Time Factors ,Heart disease ,Gestational Age ,Ventricular Outflow Obstruction ,Ultrasonography, Prenatal ,Catheterization ,Pregnancy ,Risk Factors ,Cause of Death ,Infant Mortality ,Prevalence ,medicine ,Humans ,Retrospective Studies ,business.industry ,Incidence ,Hemodynamics ,Infant, Newborn ,Infant ,Gestational age ,Fetofetal Transfusion ,Prognosis ,medicine.disease ,Surgery ,Treatment Outcome ,Echocardiography ,In utero ,Atresia ,Disease Progression ,Balloon dilation ,Female ,Morbidity ,Cardiology and Cardiovascular Medicine ,Complication ,business - Abstract
OBJECTIVES The goal of this study was to determine the prevalence and evolution of acquired right ventricular outflow tract obstruction (RVOTO) in the recipient twin in twin-twin transfusion syndrome (TTTS). BACKGROUND Twin-twin transfusion syndrome complicates 4% to 26% of diamniotic monochorionic twin gestations and is associated with high fetal morbidity and mortality. Cardiac dysfunction and biventricular hypertrophy may develop in the recipient twin with the potential for RVOTO. METHODS This was a retrospective review of a two-center experience of TTTS to describe the prevalence and evolution of acquired RVOTO in the recipient twin. Right ventricular outflow tract obstruction was diagnosed or excluded by fetal or postnatal echocardiography or clinical assessment. RESULTS Of 73 twin pregnancies with TTTS identified between 1994 to 1998, a total of seven (9.6%) were complicated by RVOTO in the recipient twin: two subvalvar/muscular, four valvar and one combined. Of 44 pregnancies with fetal echo, six had in utero RVOTO with antegrade flow diagnosed at gestational ages ranging from 19 to 27 weeks. In utero progression occurred in four cases over a period of four to eight weeks, with the development of RVOT atresia by delivery. Postnatal progression of RVOTO occurred in two cases, one of which required pulmonary balloon valvuloplasty at age two years. Postnatal regression of subvalvar RVOTO occurred in two cases in early infancy. Death related directly or indirectly to the RVOTO occurred in all four patients who developed complete RVOT obliteration. CONCLUSIONS Right ventricular outflow tract obstruction may occur in the recipient twin of at least 9% of pregnancies complicated by TTTS. Right ventricular outflow tract obstruction progression is common in utero and may worsen neonatal outcome.
- Published
- 2001
44. Impact of prenatal risk factors on congenital heart disease in the current era
- Author
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Sapna Naik, Alan Fung, Herschel Rosenberg, Cedric Manlhiot, Tapas Mondal, John Smythe, Brian W. McCrindle, David Chitayat, Seema Mital, and Jane Lougheed
- Subjects
Heart Defects, Congenital ,Male ,Pediatrics ,medicine.medical_specialty ,Heart disease ,Prenatal diagnosis ,Pregnancy ,Risk Factors ,Prenatal Diagnosis ,Medicine ,Humans ,genetics ,cardiovascular diseases ,Genetic Testing ,Prospective Studies ,Family history ,Prospective cohort study ,Genetic testing ,Original Research ,fetal cardiovascular abnormality ,medicine.diagnostic_test ,business.industry ,Infant, Newborn ,Editorials ,medicine.disease ,congenital heart disease ,Cohort ,Female ,Cardiology and Cardiovascular Medicine ,business ,Body mass index ,environment - Abstract
Background The healthcare burden related to congenital heart disease ( CHD ) is increasing with improving survival. We assessed changing trends in prenatal risk factors for CHD in the current era in a Canadian cohort. Methods and Results CHD patients ECA s), and antenatal risk factors were assessed. Temporal trends were analyzed and associations with CHD were measured using linear and logistic regression. Family history of CHD and frequency of major ECA s was higher in cases versus controls ( P CHD had a confirmed genetic diagnosis. Yield of genetic testing (ie, frequency of abnormal results) was higher in familial and syndromic cases. There was an increase in parental age at conception, maternal prepregnancy body mass index, maternal urinary tract infections, type 1 diabetes, and exposure to nonfertility medications during pregnancy from 1990–2011. Later year of birth, family history of CHD , presence of major ECA s, maternal smoking during pregnancy, and maternal medication exposure were associated with increased odds of CHD ( P CHD caused by genetic abnormalities. Conclusions The increase in prenatal risk factors for CHD highlights the need for more rigorous ascertainment of genetic and environmental factors including gene‐environment interactions that contribute to CHD .
- Published
- 2013
45. Presentation, diagnosis, and medical management of heart failure in children: Canadian Cardiovascular Society guidelines
- Author
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Adrian Dancea, Kristen George, Joseph Atallah, Robert D. Ross, Michelle M. Graham, Carol Chan, Beth Kauffman, Thomasin Adams-Webber, Steven C. Greenway, Mark K. Friedberg, Derek G. Human, Jack F. Price, Sarah Bowdin, Catherine Chant-Gambacort, Reeni Soni, Melanie D. Everitt, Robert S. McKelvie, Kenny K. Wong, Ashok Kakadekar, Judith Wilson, Michael McGillion, Suryakant Shah, Lars Grosse-Wortmann, Paul F. Kantor, Elfriede Pahl, Lindsay M. Ryerson, S. Lucy Roche, J. Conway, Aamir Jeewa, Julian Raiman, J.E. Potts, Jane Lougheed, Holger Buchholz, Seema Mital, Christian Drolet, Nicole Barbosa, John L. Jefferies, Letizia Gardin, Daphne T. Hsu, Charles E. Canter, Rejane Dillenburg, and Elizabeth A. Stephenson
- Subjects
Heart Defects, Congenital ,medicine.medical_specialty ,Pediatrics ,Canada ,Cardiotonic Agents ,Heart disease ,Adolescent ,Vasopressins ,Vasodilator Agents ,Diagnostico diferencial ,Management of heart failure ,MEDLINE ,Angiotensin-Converting Enzyme Inhibitors ,Diagnosis, Differential ,Catecholamines ,Risk Factors ,Medicine ,Humans ,Intensive care medicine ,Grading (education) ,Child ,Diuretics ,Arrhythmogenic Right Ventricular Dysplasia ,Societies, Medical ,Heart Failure ,Evidence-Based Medicine ,business.industry ,Myocardium ,Infant ,Evidence-based medicine ,Canadian Cardiovascular Society ,medicine.disease ,Prognosis ,Combined Modality Therapy ,Magnetic Resonance Imaging ,Myocarditis ,Death, Sudden, Cardiac ,Echocardiography ,Heart failure ,Child, Preschool ,Electrocardiography, Ambulatory ,Cardiology and Cardiovascular Medicine ,business ,Cardiomyopathies ,Angiotensin II Type 1 Receptor Blockers ,Algorithms ,Biomarkers - Abstract
Pediatric heart failure (HF) is an important cause of morbidity and mortality in childhood. This article presents guidelines for the recognition, diagnosis, and early medical management of HF in infancy, childhood, and adolescence. The guidelines are intended to assist practitioners in office-based or emergency room practice, who encounter children with undiagnosed heart disease and symptoms of possible HF, rather than those who have already received surgical palliation. The guidelines have been developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and are accompanied by practical Recommendations for their application in the clinical setting, supplemented by online material. This work does not include Recommendations for advanced management involving ventricular assist devices, or other device therapies.
- Published
- 2012
46. Horseshoe lung and facio-auriculo-vertebral sequence: a previously unreported association
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Alasdair G. W. Hunter, Lisa C.A. D'Alessandro, Joseph Reisman, Tom Kovesi, Jane Lougheed, and Sherief Massoud
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Pulmonary and Respiratory Medicine ,Heart Defects, Congenital ,Goldenhar syndrome ,Ribs ,Scimitar syndrome ,medicine ,Diseases in Twins ,Humans ,Abnormalities, Multiple ,Lung ,business.industry ,Respiratory disease ,Infant, Newborn ,Dysostosis ,Anatomy ,Twins, Monozygotic ,respiratory system ,medicine.disease ,Hypoplasia ,Spine ,Vertebra ,Hemifacial microsomia ,medicine.anatomical_structure ,Face ,Pediatrics, Perinatology and Child Health ,Female ,Hemivertebrae ,business - Abstract
We describe a case of horseshoe lung in an infant with facio-auriculo-vertebral (FAV) sequence that included mild hemifacial microsomia, ear anomalies, a missing left rib, left hemivertebrae (T2-T4), and complex congenital heart disease. Of the approximately 40 cases of horseshoe lung described since 1962, most are reported in association with scimitar syndrome, and only four reported cases were associated with left lung hypoplasia. None of these cases included malformations consistent with a diagnosis of FAV sequence.
- Published
- 2006
47. The prevention of congenital anomalies with periconceptional folic acid supplementation
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Sarah E. Ferguson, Jane Lougheed, Sarah D. McDonald, Mark Walker, and Larissa E. Tam
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Heart Defects, Congenital ,medicine.medical_specialty ,Pediatrics ,law.invention ,Congenital Abnormalities ,Folic Acid ,Randomized controlled trial ,law ,Pregnancy ,medicine ,Humans ,Neural Tube Defects ,Randomized Controlled Trials as Topic ,Gynecology ,Neural tube defect ,business.industry ,Incidence (epidemiology) ,Neural tube ,Obstetrics and Gynecology ,medicine.disease ,Folic acid supplementation ,Clinical trial ,medicine.anatomical_structure ,Folic acid ,Fertilization ,Dietary Supplements ,Practice Guidelines as Topic ,Female ,business - Abstract
Large randomized trials have demonstrated the critical role of folic acid supplementation in the prevention of neural tube defects. Since 1992, a number of national and international professional societies have released guidelines recommending folic acid supplementation of at least 0. 4 mg/day for all women of childbearing age or women planning pregnancies, and 4 mg/day for women with a previous infant with a neural tube defect. Furthermore, a reduction in the incidence of congenital cardiac and urologie anomalies has been demonstrated in some studies following periconceptional folic acid supplementation. There is growing evidence of a possible role of folic acid supplementation in the prevention of other congenital anomalies, including cardiac defects. Since 1998, mandatory fortification of certain foods with folate has been associated with at least a 54% reduction in the incidence of open neural tube defects, yet rates of periconceptional folic acid use remain suboptimal, especially in minority women. Innovative strategies in educating women, health-care providers, and pharmacists on the benefits of folic acid supplementation need to be explored. Mandatory folate fortification of foods needs to be defined and monitored.
- Published
- 2003
48. Fetal heterotaxy syndrome: spectrum of heart disease, accuracy of diagnosis, and clinical outcome
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Jeffrey F. Smallhorn, Lisa K. Hornberger, Mio Taketazu, Jane Lougheed, and Shi-Joon Yoo
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Pediatrics ,medicine.medical_specialty ,Fetus ,Heart disease ,Heterotaxy Syndrome ,business.industry ,medicine ,Cardiology and Cardiovascular Medicine ,medicine.disease ,business ,Outcome (game theory) - Published
- 2002
49. Horseshoe lung and facio‐auriculo‐vertebral sequence: A previously unreported association.
- Author
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Lisa D'Alessandro, Tom Kovesi, Sherief Massoud, Jane Lougheed, Alasdair Hunter, and Joseph Reisman
- Published
- 2006
- Full Text
- View/download PDF
50. Cardiac risk assessment before the use of stimulant medications in children and youth: A joint position statement by the Canadian Paediatric Society, the Canadian Cardiovascular Society and the Canadian Academy of Child and Adolescent Psychiatry
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Shubhayan Sanatani, John C. LeBlanc, Robert M. Hamilton, Russell Schachar, Andrew E. Warren, M Weiss, B Miles, Gorman Da, Robert M. Gow, Stacey Ageranioti Bélanger, Martin S, Clare Gray, C Mitchell, Jane Lougheed, and Côté Jm
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Male ,Canada ,medicine.medical_specialty ,Adolescent ,Clinical Perspectives ,Population health ,Risk Assessment ,Sudden death ,Drug Administration Schedule ,Electrocardiography ,Sex Factors ,Sickness Impact Profile ,medicine ,Child and adolescent psychiatry ,Humans ,Mass Screening ,Attention deficit hyperactivity disorder ,Child ,Position Statement ,Psychiatry ,Mass screening ,Dose-Response Relationship, Drug ,business.industry ,Age Factors ,Canadian Cardiovascular Society ,Guideline ,medicine.disease ,Death, Sudden, Cardiac ,Treatment Outcome ,Attention Deficit Disorder with Hyperactivity ,Cardiovascular Diseases ,Child, Preschool ,Central Nervous System Stimulants ,Female ,Cardiology and Cardiovascular Medicine ,Risk assessment ,business ,Follow-Up Studies - Abstract
Regulatory decisions and scientific statements regarding the management of attention-deficit hyperactivity disorder (ADHD) raise questions about the safety of medications and the appropriate pretreatment evaluation to determine suitability for treatment with medication. This is particularly true in the setting of known structural or functional heart disease. The present paper reviews the available data, including peer-reviewed literature, data from the United States Food and Drug Administration Web site on reported adverse reactions in children using stimulant medication, and Health Canada data on the same problem. A consensus-based guideline on appropriate assessment is provided, based on input from members of the Canadian Paediatric Society, the Canadian Cardiovascular Society and the Canadian Academy of Child and Adolescent Psychiatry, with specific expertise and knowledge in the areas of both ADHD and pediatric cardiology. The present statement advocates a thorough history and physical examination before starting stimulant medications, with an emphasis on the identification of risk factors for sudden death, but does not routinely recommend electrocardiographic screening or cardiac subspecialist consultation unless indicated by history or physical examination findings. A checklist for identifying children who are potentially at risk of sudden death (independent of ADHD or medications used to treat it) is provided. Although recommendations are based on the best evidence currently available, the committee further agrees that more research on this subject is necessary to optimize the approach to this common clinical scenario.
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