The Quebec Congenital Heart Disease Registry: A Model of Prospective Databank to Facilitate Research in Congenital Cardiology.

Background: A national registry of congenital heart disease (CHD) would facilitate project initiation, decrease costs, increase statistical power, and avoid duplication. Establishing such registries poses numerous challenges, but the current Canadian research ecosystem in CHD is well positioned to meet them. We assessed the feasibility of building a province-wide CHD registry by automatically identifying people with CHD and extracting their native cardiac anatomy from multiple clinical data sources, without the need for manual data entry. Methods: We designed a CHD registry of all fetuses and children with at least 1 echocardiographic report confirming CHD since 2000. We interfaced the registry with several clinical and echocardiography data sources from all paediatric cardiology programmes in Québec. Results: We extracted 885,287 echocardiogram reports and 70,121 clinical records. We identified CHD in 43,452 children and 4682 fetuses. There were 1128 (2.3%) cases with files in multiple institutions, and patients with more complex CHD were 3 times more likely to be seen in more than 1 institution. So far, the registry has been used to build and link CHD cohorts for 7 distinct projects. Conclusions: We demonstrated the feasibility of a baseline CHD registry in Québec without the need for manual data entry, in which other CHD research projects could be nested. This could serve as a blueprint to expand the registry and to develop an integrated approach where data gathered in caring for patients with CHD serve as data layers that incrementally contribute to a national cohort, for which data remain easily accessible and usable.

Contexte: Un registre national des cardiopathies congénitales (CC) pourrait faciliter le lancement de projets de recherche, en diminuer les coûts, en améliorer la puissance statistique tout en évitant les redondances. La mise en place de tels registres pose de nombreux défis, mais l'écosystème de recherche canadien dans le domaine de la CC est bien placé pour y répondre. Nous avons évalué la faisabilité de la mise en place d'un registre des CC à l'échelle provinciale par l'identification automatique des personnes atteintes de CC et l'extraction de leur anatomie cardiaque native à partir de plusieurs sources de données cliniques, sans nécessiter de saisie manuelle de données. Méthodologie: Nous avons conçu un registre des CC incluant tous les fœtus et les enfants pour qui au moins un rapport d'évaluation électrocardiographique confirmait la présence d'une CC depuis 2000. Le registre a été mis en relation avec plusieurs sources de données cliniques et échocardiographiques provenant de tous les programmes en cardiologie pédiatrique au Québec. Résultats: Nous avons extrait 885 287 rapports d'échocardiographie et 70 121 dossiers cliniques. La présence d'une CC a été établie chez 43 452 enfants et 4 682 fœtus. Dans 1 128 cas (2,3 %), un dossier existait dans plus d'un établissement. Les patients présentant des CC plus complexes étaient 3 fois plus susceptibles d'être suivis dans plus d'un établissement. Jusqu'à présent, le registre a été utilisé pour établir et mettre en relation des cohortes de patients atteints de CC pour sept projets de recherche distincts. Conclusions: Nous avons démontré la faisabilité de la mise en place d'un registre de référence des CC au Québec sans recours à la saisie manuelle de données, dans lequel peuvent se nicher d'autres projets de recherche sur les CC. Notre démarche pourrait servir de prototype pour une expansion du registre et pour une approche d'intégration des données recueillies dans la prestation de soins aux patients atteints de CC, afin de former des couches de données qui s'ajoutent au fur et à mesure à une cohorte nationale, avec des données faciles à obtenir et à utiliser.

The Detection, Evaluation, and Management of Dyslipidemia in Children and Adolescents: A Canadian Cardiovascular Society/Canadian Pediatric Cardiology Association Clinical Practice Update.

Atherosclerosis begins in youth and is directly linked with the presence and severity of cardiovascular risk factors, including dyslipidemia. Thus, the timely identification and management of dyslipidemia in childhood might slow atherosclerotic progression and decrease the risk of cardiovascular disease in adulthood. This is particularly true for children with genetic disorders resulting in marked dyslipidemia, including familial hypercholesterolemia, which remains frequently undiagnosed. Universal and cascade screening strategies can effectively identify cases of pediatric dyslipidemia. In the clinical evaluation of children with dyslipidemia, evaluating for secondary causes of dyslipidemia, including medications and systemic disorders is essential. The first line therapy generally centres around lifestyle modifications, with dietary changes specific to the dyslipidemia phenotype. Indications for medication depend on the severity of dyslipidemia and an individualized assessment of cardiovascular risk. Despite an expanding evidence base supporting the detection and timely management of pediatric dyslipidemia, numerous knowledge gaps remain, including a sufficient evidence base to support more widespread screening, thresholds for initiation of pharmacotherapy, and treatment targets. Further studies on the most appropriate age for statin initiation and long-term safety studies of statin use in youth are also required. The most pressing matter, however, is the development of knowledge translation strategies to improve the screening and detection of lipid disorders in Canadian youth.

Incremental Detection of Severe Congenital Heart Disease by Fetal Echocardiography Following a Normal Second Trimester Ultrasound Scan in Québec, Canada.

BACKGROUND: The benefit of fetal echocardiograms (FE) to detect severe congenital heart diseases (SCHD) in the setting of a normal second-trimester ultrasound is unclear. We aimed to assess whether the increase in SCHD detection rates when FE are performed for risk factors in the setting of a normal ultrasound was clinically significant to justify the resources needed. METHODS: This is a multicenter, population-based, retrospective cohort study, including all singleton pregnancies and offspring in Quebec (Canada) between 2007 and 2015. Administrative health care data were linked with FE clinical data to gather information on prenatal diagnosis of CHD, indications for FE, outcomes of pregnancy and offspring, postnatal diagnosis of CHD, cardiac interventions, and causes of death. The difference between the sensitivity to detect SCHD with and without FE for risk factors was calculated using generalized estimating equations with a noninferiority margin of 5 percentage points. RESULTS: A total of 688 247 singleton pregnancies were included, of which 30 263 had at least one FE. There were 1564 SCHD, including 1071 that were detected prenatally (68.5%). There were 12 210 FE performed for risk factors in the setting of a normal second-trimester ultrasound, which led to the detection of 49 additional cases of SCHD over 8 years. FE referrals for risk factors increased sensitivity by 3.1 percentage points (95% CI, 2.3-4.0; P<0.0001 for noninferiority). CONCLUSIONS: In the setting of a normal second-trimester ultrasound, adding a FE for risk factors offered low incremental value to the detection rate of SCHD in singleton pregnancies. The current ratio of clinical gains versus the FE resources needed to screen for SCHD in singleton pregnancies with isolated risk factors does not seem favorable. Further studies should evaluate whether these resources could be better allocated to increase SCHD sensitivity at the ultrasound level, and to help decrease heterogeneity between regions, institutions and operators.

Cardiac Left Ventricle Mitochondrial Dysfunction After Neonatal Exposure to Hyperoxia: Relevance for Cardiomyopathy After Preterm Birth.

BACKGROUND: Individuals born preterm present left ventricle changes and increased risk of cardiac diseases and heart failure. The pathophysiology of heart disease after preterm birth is incompletely understood. Mitochondria dysfunction is a hallmark of cardiomyopathy resulting in heart failure. We hypothesized that neonatal hyperoxia in rats, a recognized model simulating preterm birth conditions and resulting in oxygen-induced cardiomyopathy, induce left ventricle mitochondrial changes in juvenile rats. We also hypothesized that humanin, a mitochondrial-derived peptide, would be reduced in young adults born preterm. METHODS: Sprague-Dawley pups were exposed to room air (controls) or 80% O2 at postnatal days 3 to 10 (oxygen-induced cardiomyopathy). We studied left ventricle mitochondrial changes in 4 weeks old males. In a cohort of young adults born preterm (n=55) and age-matched term (n=54), we compared circulating levels of humanin. RESULTS: Compared with controls, oxygen-exposed rats showed smaller left ventricle mitochondria with disrupted integrity on electron microscopy, decreased oxidative phosphorylation, increased glycolysis markers, and reduced mitochondrial biogenesis and abundance. In oxygen-exposed rats, we observed lipid deposits, increased superoxide production (isolated cardiomyocytes), and reduced Nrf2 gene expression. In the cohort, left ventricle ejection fraction and peak global longitudinal strain were similar between groups however humanin levels were lower in preterm and associated with left ventricle ejection fraction and peak global longitudinal strain. CONCLUSIONS: In conclusion, neonatal hyperoxia impaired left ventricle mitochondrial structure and function in juvenile animals. Serum humanin level was reduced in preterm adults. This study suggests that preterm birth-related conditions entail left ventricle mitochondrial alterations that may underlie cardiac changes perpetuated into adulthood. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03261609.

CARDEA study protocol: investigating early markers of cardiovascular disease and their association with lifestyle habits, inflammation and oxidative stress in adolescence using a cross-sectional comparison of adolescents with type 1 diabetes and healthy controls.

INTRODUCTION: Little is known regarding associations between potentially modifiable lifestyle habits and early markers of cardiovascular disease (CVD) in pediatric type 1 diabetes (T1D), hindering early prevention efforts. Specific objectives are: (1) compare established risk factors (dyslipidemia, hypertension) with novel early markers for CVD (cardiac phenotype, aortic distensibility, endothelial function) in adolescents with T1D and healthy age-matched and sex-matched controls; (2) examine associations between these novel early markers with: (i) lifestyle habits; (ii) adipokines and measures of inflammation; and (iii) markers of oxidative stress among adolescents with T1D and controls, and determine group differences in these associations; (3) explore, across both groups, associations between CVD markers and residential neighbourhood features. METHODS AND ANALYSES: Using a cross-sectional design, we will compare 100 participants aged 14-18 years with T1D to 100 healthy controls. Measures include: anthropometrics; stage of sexual maturity (Tanner stages); physical activity (7-day accelerometry); sleep and sedentary behaviour (self-report and accelerometry); fitness (peak oxygen consumption); and dietary intake (three non-consecutive 24- hour dietary recalls). Repeated measures of blood pressure will be obtained. Lipid profiles will be determined after a 12- hour fast. Cardiac structure/function: non-contrast cardiac magnetic resonance imaging (CMR) images will evaluate volume, mass, systolic and diastolic function and myocardial fibrosis. Aortic distensibility will be determined by pulse wave velocity with elasticity and resistance studies at the central aorta. Endothelial function will be determined by flow-mediated dilation. Inflammatory markers include plasma leptin, adiponectin, tumour necrosis factor alpha (TNF-α), type I and type II TNF-α soluble receptors and interleukin-6 concentrations. Measures of endogenous antioxidants include manganese superoxide dismutase, glutathione peroxidase and glutathione in blood. Neighbourhood features include built and social environment indicators and air quality. ETHICS AND DISSEMINATION: This study was approved by the Sainte-Justine Hospital Research Ethics Board. Written informed assent and consent will be obtained from participants and their parents. TRIAL REGISTRATION NUMBER: NCT04304729.

Left Ventricle Structure and Function in Young Adults Born Very Preterm and Association with Neonatal Characteristics.

Preterm birth increases risk of cardiovascular disease and early death. A body of evidence suggests left ventricle (LV) echocardiographic alterations in children and adults born preterm. We aimed to determine if neonatal characteristics were associated with alterations in LV structure and function in preterm adults. We evaluated a cohort of 86 young adults born preterm below 30 weeks of gestation, and 85 full-term controls. We determined LV dimensions and function using tissue Doppler imaging, conventional and speckle tracking echocardiography (STE). Adults born preterm had smaller LV dimensions, but these differences did not remain after adjustment for body surface area (BSA), which was smaller in the preterm group. Stroke volume and cardiac output were reduced even after adjustment for BSA. We found a smaller e' wave in the preterm group, but other markers of systolic and diastolic function did not differ. Use of antenatal steroids may be associated with a further reduced cardiac output in those born preterm. Adults born preterm show alterations in markers of LV dimensions and function. Identification of these markers may represent opportunities for early prevention of cardiovascular events in this at-risk population.

Determinants of attrition in a pediatric healthy lifestyle intervention: The CIRCUIT program experience.

INTRODUCTION: Attrition in pediatric weight management programs is notoriously high. Greater understanding of its determinants is needed to inform retention strategies. We identified determinants of attrition in CIRCUIT, a healthy lifestyle intervention program for youth at risk of cardiovascular disease. METHODS: A one-arm intervention study of children aged 4-18 years who initiated the CIRCUIT program in the first five years of its existence (N = 403). We defined attrition as attending the baseline visit but ceasing attendance prior to the 1-year follow-up. Potential determinants of dropout included the child's age, sex, ethnicity, body mass index (BMI) z-score, family socio-demographic characteristics, and estimated driving time to the program, all measured at baseline. Associations were estimated bivariately, using chi-squared- and t-tests, and simultaneously in a multivariable logistic regression model. RESULTS: Of the 403 participants who started the program, 198 (49%) dropped out within 12 months of enrollment. Youth who dropped out were older (mean age 12.8y vs. 11.3y; p < 0.01), were less likely to live with both parents (62% vs. 71%; p = 0.05), and to have mothers who had completed high school (79% vs. 88%; p = 0.01). No group differences were observed for sex, ethnicity, baseline BMI z-score, fathers' education, or driving time to the program. In multivariate models, only older age at initiation of the intervention (OR: 1.2; CI: 1.1,1.3) and lower maternal education (OR: 2.0; CI: 1.0,3.8) were associated with dropout. CONCLUSION: Improved tailoring of interventions to older pediatric participants and to families of lower maternal education may help reduce attrition in CIRCUIT and similar lifestyle intervention programs.

Association of Bronchopulmonary Dysplasia and Right Ventricular Systolic Function in Young Adults Born Preterm.

BACKGROUND: Adults born preterm are at a higher risk of cardiopulmonary disease and premature death. Preterm birth is associated with abnormalities in right ventricular (RV) structure and function, but the impact of bronchopulmonary dysplasia (BPD), a common complication of extremely preterm birth, on these parameters remains unknown. RESEARCH QUESTION: Are preterm birth and BPD associated with alterations in RV structure and function in early adulthood? STUDY DESIGN AND METHODS: Echocardiographic and spirometry data were obtained from the Health of Adults Born Preterm Investigation (HAPI). RV structure and performance were evaluated by using echocardiography, and respiratory function was assessed by using spirometry. RESULTS: The study comprised 86 young adults born preterm before 30 weeks of gestation, including 28 with moderate to severe BPD, and 85 adults of the same age born full term. Individuals were assessed at a mean age of 23 years. RV systolic function was altered in the preterm group, with lower tricuspid annular plane systolic excursion and lower RV s' and RV outflow tract velocity time integral values, especially in those born preterm with BPD. Nine (36%) participants born preterm with BPD, six (13%) participants born preterm without BPD, and six (8%) participants born full term had a tricuspid annular plane systolic excursion value < 16 mm, a marker of RV systolic dysfunction (P value for the comparison between preterm no BPD and BPD, .032). No difference was found in RV diastolic function or estimates of pulmonary artery pressure between groups. Although respiratory function was altered in those born preterm, and more so in the case of BPD, no association was observed between spirometry indices of respiratory function and RV systolic function. INTERPRETATION: Preterm birth is associated in adulthood with alterations in RV systolic function, which are more pronounced in the case of BPD. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03261609; URL: www.clinicaltrials.gov.

Promoting healthy lifestyle behaviours in youth: Findings from a novel intervention for children at risk of cardiovascular disease.

OBJECTIVES: Obesity is the most prevalent risk factor for cardiovascular disease (CVD) in children. We developed a 2-year lifestyle intervention for youth at risk of CVD. We assessed changes in body mass index z-scores (zBMI) and key cardiometabolic risk factors, physical fitness, and capacity among those who completed the program. METHODS: The CIRCUIT program is a multidisciplinary lifestyle intervention for children aged 4 to 18 years at risk of CVD, based on a personalized plan to improve cardiometabolic outcomes by increasing physical activity and reducing sedentary behaviours. Both at baseline and 2-year follow-up, we measured zBMI, blood pressure z-scores (zBP), adiposity (%body and %trunk fat), fasting blood glucose and lipid profile, aerobic (VO2max) and anaerobic (5×5 m shuttle run test) fitness, and physical capacity indicators. Differences between baseline and follow-up were examined using paired t-tests (for age-sex standardized outcomes) and multivariable mixed effect models, adjusted for age and sex (for other outcomes). RESULTS: Among the 106 participants (53 males) who completed the 2-year program, mean age at baseline was 10.9 years (SD=3.2). After 2 years, zBMI and diastolic zBP decreased by 0.30SD (95% CI: -0.44; -0.16) and 0.43SD (95% CI: -0.65; -0.23), respectively. Participants improved %body and %trunk fat, lipid profile, aerobic and anaerobic fitness levels, and physical capacity (p<0.02). No changes in systolic zBP nor in fasting plasma glucose were observed. CONCLUSION: Our findings showed improved zBMI, cardiometabolic outcomes, physical fitness, and capacity among children at risk of CVD, suggesting that CIRCUIT is a promising intervention.

Arterial Structure and Stiffness Are Altered in Young Adults Born Preterm.

OBJECTIVE: Preterm birth has been associated with changes in arterial structure and function. Association with complications occurring during the neonatal period, including bronchopulmonary dysplasia, on vascular outcomes in adulthood is unknown. Approach and Results: We evaluated a cohort of 86 adults born preterm (below 30 weeks of gestation), compared to 85 adults born term, at a mean age of 23 years. We performed ultrasonographic assessment of the dimensions of the ascending aorta, carotid and brachial arteries, and estimated flow-mediated dilation, carotid-femoral pulse wave velocity, augmentation index corrected for heart rate, and carotid intima-media thickness. All analyses were performed with and without adjustment for potential confounding variables, including height, sex, and body mass index. Ascending aorta diameter in diastole was smaller in the preterm group, but carotid and brachial arteries were similar. Carotid and brachial strain, a marker of arterial distensibility, was smaller in the preterm group, while carotid-femoral pulse wave velocity, was similar between groups, indicating similar aortic stiffness. Carotid intima-media thickness, endothelial function flow-mediated dilation, blood nitrite, and nitrate levels were similar between groups. Individuals with bronchopulmonary dysplasia had lower brachial artery strain suggesting long-term association of this neonatal complication with vascular structure. Diastolic blood pressure was higher in the preterm group and was associated with decreased brachial and carotid distensibility. CONCLUSIONS: Young adults born preterm display alterations in arterial distensibility that are associated with a history of bronchopulmonary dysplasia.

Cardiovascular Risk Factors in Patients With Congenital Heart Disease.

Survival of infants born with congenital heart disease (CHD) is improving tremendously and although most of them have mild lesions, others might be considered as only being palliated and undergo many medical or surgical interventions. Patients with CHD will be exposed to the same problematic of the modern lifestyle such as increased prevalence of obesity, decreased physical activities, and exposure to smoking, which leads to acquired cardiovascular disease. We specifically investigated specific cardiovascular risk factors such as: malnutrition, smoking exposure, hypertension, integrity of the coronary and systemic arteries, thromboembolism, ventricular dysfunction, inflammation, and arrhythmias. Patients with CHD are often submitted to extremes of nutrition: as infants, they often do not meet their metabolic requirements, and as they grow older, they tend to exceed them, as seen in the general population. Some heart lesions are more prone to systemic hypertension throughout life, such as coarctation of the aorta, but surprisingly other lesions are also prone to hypertension such as Ebstein anomaly, pulmonary valve stenosis, or regurgitation. Early coronary artery atherosclerosis is also a concern in these patients. Lesions typically at risk are localized in zones of increased turbulence or high pressure or having had previous surgical manipulations. Thromboembolism is also frequent and mostly associated with arrhythmias, heart failure, multiple catheterizations, and specific surgical repairs. Finally, the complexity of heart lesions or abnormal hemodynamics lead to inflammation, heart failure, or arrhythmias. These complex interactions of risk factors ultimately lead to a decreased life expectancy.

Can anthropometry and physical fitness testing explain physical activity levels in children and adolescents with obesity?

OBJECTIVES: As time with patients and resources are increasingly limited, it is important to determine if clinical tests can provide further insight into real-world behaviors linked to clinical outcomes. The purpose of this study was to determine which aspects of anthropometry and physical fitness testing are associated with physical activity (PA) levels among youth with obesity. DESIGN: Cross-sectional study. METHOD: Anthropometry [height, waist circumference, bodyweight, fat percentage], physical fitness [muscular endurance (partial curl-ups), flexibility (sit-and-reach), lower-body power (long-jump), upper-body strength (grip), speed/agility (5×5-m shuttle), cardiorespiratory fitness (VO2-max)], and PA [light (LPA), moderate (MPA), vigorous (VPA), MVPA] was assessed in 203 youth with obesity. RESULTS: The sample was stratified by age <12 yrs (children); 12 yrs (adolescents) and sex. Stepwise regression evaluated associations between PA with anthropometry and physical fitness. Children (57% male) and adolescents (45% male) had a BMI Z-score of 3.5(SD:0.94) and 3.1(SD:0.76) respectively. Long-jump explained 19.5% [(Standardized) Beta=0.44; p=0.001] of variance in VPA for childhood girls and 12.6% (Beta=0.35; p=0.025) of variance in MPA for adolescent boys. 5×5-m shuttle explained 8.4% (Beta=-0.29; p=0.042) of variance in MVPA for childhood girls. Body mass explained 6.3% (Beta=-0.25; p=0.007) of variance in LPA in childhood boys. Fat percentage explained 9.8% (Beta=0.31; p=0.03) of variance in MPA in adolescent girls. CONCLUSIONS: In conclusion, tests of lower body power, body mass and fat percentage provide limited information concerning PA levels in youth with obesity. Activity monitoring should be considered in addition to clinical assessments to more fully understand youth health.

Motor Skills of Children and Adolescents With Obesity and Severe Obesity-A CIRCUIT Study.

Häcker, A-L, Bigras, J-L, Henderson, M, Barnett, TA, and Mathieu, M-E. Motor skills of children and adolescents with obesity and severe obesity-a CIRCUIT study. J Strength Cond Res 34(12): 3577-3586, 2020-During childhood, excessive weight is negatively associated with the development of motor skills, with overweight children or children with obesity having poorer motor skills compared with children with normal weight. The objectives of the current study are to identify the differences in motor skills between children and adolescents with obesity and severe obesity and the extent of this difference. To do so, we examined cross-sectionally 165 subjects. Physical fitness was analyzed in both subjects with obesity (>97th to 99.9th body mass index [BMI] percentile) and severe obesity (>99.9th BMI percentile) using 8 standardized tests: sit-and-reach, grip force, sit-ups, push-ups, balance, hand-eye coordination, standing long jump and 5-m shuttle run. Poorer performance were observed in subjects with severe obesity in sit-ups (children: 59%; 18.6 ± 17.0 vs. 29.5 ± 23.2 percentile value, p = 0.008), balance (adolescent: 59%; 12.1 ± 12.2 vs. 19.3 ± 13.9 seconds, p = 0.034), and in the 5-m shuttle run (children: 49%; 14.0 ± 13.9 vs. 20.8 ± 19.4 percentile value, p = 0.046; adolescents: 11%; 13.2 ± 2.2 vs. 11.8 ± 1.6 seconds, p = 0.008) compared with obese counterparts. In conclusion, although physical performance was found to be similar between the different obesity levels for most tests, youth with severe obesity demonstrated impairments ranging from 11 to 59% in specific tests.

Rationale and Design of the FREQUENCY Study: The Fetal Cardiac Registry of Québec to Improve Resource Utilization in Fetal Cardiology.

OBJECTIVE: Prenatal detection of congenital heart diseases (CHD) decreases morbidity and cost. To improve detections rates, most physicians refer pregnant women with high-risk pregnancies to fetal cardiologists even when there is no suspicion of CHD at the second trimester screening. This paper presents the rationale and detailed method of the Fetal Cardiac Registry of Québec to Improve Resource Utilization in Fetal Cardiology (FREQUENCY) study. The overall objective is to assess the impact of second trimester ultrasound screening (U/S) and referral pattern in fetal cardiology on detection rates, health care costs, and resource utilization, as well as perinatal morbidity and mortality. METHODS: This multicentre retrospective population-based cohort study will link fetal echocardiography data from all centres performing fetal echocardiography in Québec with administrative health care data. This data linking will allow the determination of a true denominator (all women in Québec who underwent second trimester U/S) with complete follow-up of up to 2 years for offspring. This protocol meets Canadian Task Force Classification II-2. RESULTS: The study investigators have collected and cleaned fetal echocardiography data for 24 259 eligible pregnancies referred to fetal cardiology. These data will be matched to approximately 860 000 pregnancies between 2007 and 2015. CONCLUSION: The results of the FREQUENCY study will shed light on the impact of the current prenatal CHD screening strategy in Canada.

Endothelial Colony-Forming Cells in Young Adults Born Preterm: A Novel Link Between Neonatal Complications and Adult Risks for Cardiovascular Disease.

BACKGROUND: Preterm birth is linked to cardiovascular risks and diseases. Endothelial progenitor cells play a critical role in vascular development and repair. Cord blood endothelial progenitor cells of preterm-born infants, especially endothelial colony-forming cells (ECFC), show enhanced susceptibility to prematurity-related pro-oxidant stress. Whether ECFC dysfunction is present in adulthood following preterm birth is unknown. METHODS AND RESULTS: This cross-sectional observational study includes 55 preterm-born (≤29 gestational weeks) young adults (18-29 years old, 38% male) and 55 sex- and age-matched full-term controls. ECFC were isolated from peripheral blood; cell proliferative and vascular cord formation capacities were assessed in vitro. Daytime systolic blood pressure was higher, whereas glucose tolerance and body mass index were lower in preterm-born subjects. ECFC colonies grew in culture for 62% of full-term- and 58% of preterm-born participants. Preterm-born participants have formed ECFC colonies later in culture and have reduced proliferation compared with controls. Only in preterm-born individuals, we observed that the later the ECFC colony grows in culture, the worse was overall ECFC function. In addition, in preterms, elevated systolic blood pressure significantly correlated with reduced ECFC proliferation (rS=-0.463; P=0.030) and numbers of branches formed on matrigel (rS=-0.443; P=0.039). In preterm-born subjects, bronchopulmonary dysplasia was associated with impaired ECFC function, whereas exposure to antenatal steroids related to better ECFC function. CONCLUSIONS: This study is the first to examine ECFC in preterm-born adults and to demonstrate ECFC dysfunction compared with full-term controls. In the preterm-born group, ECFC dysfunction was associated with bronchopulmonary dysplasia, the major prematurity-related neonatal morbidity, and with increased systolic blood pressure into adulthood.

The Epigenetic Machinery in Vascular Dysfunction and Hypertension.

Hypertension (HT) is among the major components of the metabolic syndrome, i.e., obesity, dyslipidemia, and hyperglycemia/insulin resistance. It represents a significant health problem with foremost risks for chronic cardiovascular disease and a significant cause of morbidity and mortality worldwide. Therefore, it is not surprising that this disorder constitutes a serious public health concern. Although multiple studies have stressed the multifactorial nature of HT, the pathogenesis remains largely unknown. However, if we want to reduce the global prevalence of HT, restrain the number of deaths (currently 9.4 million/year in the world), and alleviate the socio-economic burden, a deeper insight into the mechanisms is urgently needed in order to define new meaningful therapeutic targets. Recently, the role of epigenetics in the development of various complex diseases has attracted much attention. In the present review, we provide a critical update on the available literature and ongoing research regarding the epigenetic modifications of genes involved in several pathways of elevated blood pressure, especially those linked to the vascular epithelium. This review also focuses on the role of microRNA (miRNA) in the regulation of gene expression associated with HT and of fetal programming mediating susceptibility to HT in adulthood.

Physical Activity Programs with Post-Intervention Follow-Up in Children: A Comprehensive Review According to Categories of Intervention.

Only 9% of Canadian children meet the National Guidelines of 60 min of daily moderate-to-vigorous intensity physical activity. The aim of this review is to assess the mid- and long-term effectiveness of physical activity interventions and their impact on cardiovascular risk factors in children. We assessed the success of interventions within three different categories: those using a behavioural and social approach, an informational approach or an environmental approach. The average number of children included in these studies was 860 (range of 30-5106); the age range was from 2 to 18 years; and the mean intervention duration was 1607 min (range of 12-8160 min). The length of follow-up post-intervention averaged 13 months (ranging from 0.25 to 96 months). A positive impact on physical activity was found in 74% and on any measured outcomes in 90% of the studies reviewed. However, the benefits of physical activity interventions decreased with longer follow-up. Regardless of the approaches, physical activity interventions improved cardiovascular risk factors. However, the challenge of any program is to maintain beneficial effects once the intervention is completed. These findings will inform the development of future intervention programs in order to optimize sustained cardiovascular benefits.

'Life in the age of screens': parent perspectives on a 24-h no screen-time challenge.

Screens have become ubiquitous in modern society. Their use frequently underlies sedentary behaviour, a well-established determinant of obesity. As part of a family oriented clinic offering a 2-year lifestyle program for obese children and youth, we explored parents' experiences with a 24-h no screen-time challenge, an intervention designed to raise awareness of screen-time habits and to help families develop strategies to limit their use. In total, 15 parents representing 13 families participated. A focus group with nine parents and six phone interviews with those who could not join in person were conducted. Interviews were transcribed verbatim and analysed qualitatively. Key elements to successful completion of the 24-h no screen-time challenge emerged, namely: clear rules about permitted activities during the 24-h period; togetherness, i.e. involving all family members in the challenge; and busyness, i.e. planning a full schedule in order to avoid idleness and preclude the temptation to use screens. Our findings suggest that practitioners aiming to increase awareness of screen-time or to limit their use may be more likely to succeed if they include all family members, offer concrete alternatives to screen-based activities and provide tailored strategies to manage discretionary time.

Reference Values and Z Scores for Pulsed-Wave Doppler and M-Mode Measurements in Fetal Echocardiography.

BACKGROUND: Fetal echocardiography is now the standard approach for detailed investigations of fetal cardiac anatomy and function. Available studies proposing reference values for pulsed-wave Doppler (PWD) measurements are often focused on few parameters. Furthermore, the methodology used for validating these proposed reference values is sometimes insufficiently described, and parameters necessary to compute Z scores are not always available. Improved definition of reference values with adequate statistical validation is needed for proper interpretation of PWD measurements in a clinical setting. In this study, the authors propose a comprehensive set of reference values and Z score equations for fetal PWD and M-mode measurements with thorough assessment of Z score quality and validity. METHODS: Women with normal singleton pregnancies between 18 and 39 weeks of gestational age were included. A set of 57 measurements was performed, including PWD, M-mode measurements, and calculation of systolic, diastolic, and global function indices. Several parametric regressions were tested to model each measurement against gestational age. The SD was also modeled to account for heteroscedasticity. Z score equations were computed, and the proposed reference values were tested for residual association, residual heteroscedasticity, and departure from the normal distribution. RESULTS: One hundred four uncomplicated singleton pregnancies with normal fetal hearts were included. Nonlinear relationships with gestational age were found for most measurements. Parametric normalization was successful for most measurements analyzed, and it was possible to compute Z score equations with minimal residual association with gestational age, no residual heteroscedasticity, and no significant departure from the normal distribution. CONCLUSIONS: The authors propose a comprehensive set of Z score equations for 57 fetal functional measurements, some of which do not have any published reference values. These Z score equations will allow echocardiographers to more accurately identify measurements that diverge from normal and thus detect earlier potential alterations in fetal heart function.