Maternal occupational exposure and congenital heart defects in offspring

Objectives Congenital heart defects (CHD) are the most prevalent congenital anomalies. This study aims to examine the association between maternal occupational exposures to organic and mineral dust, solvents, pesticides, and metal dust and fumes and CHD in the offspring, assessing several subgroups of CHD. Methods For this case-control study, we examined 1174 cases with CHD from EUROCAT Northern Netherlands and 5602 controls without congenital anomalies from the Lifelines cohort study. Information on maternal jobs held early in pregnancy was collected via self-administered questionnaires, and job titles were linked to occupational exposures using a job exposure matrix. Results An association was found between organic dust exposure and coarctation of aorta [adjusted odds ratio (OR adj) 1.90, 95% confidence interval (CI) 1.01-3.59] and pulmonary (valve) stenosis in combination with ventricular septal defect (OR adj2.68, 95% CI 1.07-6.73). Mineral dust exposure was associated with increased risk of coarctation of aorta (OR adj2.94, 95% CI 1.21-7.13) and pulmonary valve stenosis (OR adj1.99, 95% CI 1.10-3.62). Exposure to metal dust and fumes was infrequent but was associated with CHD in general (OR adj2.40, 95% CI 1.09-5.30). Exposure to both mineral dust and metal dust and fumes was associated with septal defects (OR adj3.23, 95% CI 1.14-9.11). Any maternal occupational exposure was associated with a lower risk of aortic stenosis (OR adj0.32, 95% CI 0.11-0.94). Conclusions Women should take preventive measures or avoid exposure to mineral and organic dust as well as metal dust and fumes early in pregnancy as this could possibly affect foetal heart development

Decreased Muscle Strength in Children With Repaired Tetralogy of Fallot:Relation With Exercise Capacity

Background: The aim of this study is to describe muscle strength in pediatric patients with repaired tetralogy of Fallot compared with healthy peers and to analyze the correlation between muscle strength and peak oxygen uptake, exercise capacity (mL/min).Methods and Results: A prospective, cross-sectional study was carried out in the University Medical Center Groningen between March 2016 and December 2019, which included 8 -to-19-year-old patients with repaired tetralogy of Fallot. Exclusion criteria comprised the following: Down syndrome, unstable pulmonary disease and severe scoliosis affecting pulmonary function, neuromuscular disease, and mental or physical limitations that prohibit the execution of the functional tests. Muscle strength was compared with 2 healthy pediatric cohorts from the Northern Netherlands. Handgrip strength, maximal voluntary isometric contraction, and dynamic muscle strength in correlation with peak oxygen uptake, exercise capacity (mL/min) were the main outcomes of the study. The 67 patients with repaired tetralogy of Fallot (42% female; aged 12.9 [interquartile range, 10.0-16.3] years old) were compared with healthy children. The patients showed reduced grip strength ( z-score [mean±SD] -1.5±1.2, P&lt;0.001), and total muscle strength ( z-score -0.9±1.3, P&lt;0.001). Dynamic strength (Bruininks-Oseretsky test) was significantly reduced ( z-score -0.3±0.8, P=0.001), but running, speed, and agility were normal ( z-score 0.1±0.7, P=0.4). Univariate correlation analyses showed strong correlations between absolute peak oxygen uptake, exercise capacity (mL/min), and muscle strength (grip strength r=0.83, total muscle strength r=0.88; P&lt;0.001). In multivariate analyses, including correction for age and sex, total muscle strength (B 0.3; P=0.009), and forced vital capacity (B 0.5; P=0.02) correlated with peak oxygen uptake, exercise capacity (mL/min), independent of conventional cardiovascular parameters.Conclusions: Children with repaired tetralogy of Fallot show reduced muscle strength, which strongly correlated with their exercise performance. </p

Health-Related Quality of Life, Emotional and Behavioral Problems in Children and Adolescents with Ebstein Anomaly

Contains fulltext : 230135.pdf (Publisher’s version ) (Open Access

Predicting outcome in children with dilated cardiomyopathy:the use of repeated measurements of risk factors for outcome

Aims We aimed to determine whether in children with dilated cardiomyopathy repeated measurement of known risk factors for death or heart transplantation (HTx) during disease progression can identify children at the highest risk for adverse outcome. Methods and results Of 137 children we included in a prospective cohort, 36 (26%) reached the study endpoint (SE: all-cause death or HTx), 15 (11%) died at a median of 0.09 years [inter-quartile range (IQR) 0.03-0.7] after diagnosis, and 21 (15%) underwent HTx at a median of 2.9 years [IQR 0.8-6.1] after diagnosis. Median follow-up was 2.1 years [IQR 0.8-4.3]. Twenty-three children recovered at a median of 0.6 years [IQR 0.5-1.4] after diagnosis, and 78 children had ongoing disease at the end of the study. Children who reached the SE could be distinguished from those who did not, based on the temporal evolution of four risk factors: stunting of length growth (-0.42 vs. -0.02 length Z-score per year, P 6 years at presentation (all P < 0.001) were predictive of adverse outcome. In multivariate analysis, NT-proBNP appeared the only independent predictor for adverse outcome, a two-fold higher NT-proBNP was associated with a 2.8 times higher risk of the SE (hazard ratio 2.78, 95% confidence interval 1.81-3.94, P < 0.001). Conclusions The evolution over time of NT-proBNP, LVIDd, length growth, and NYU PHFI identified a subgroup of children with dilated cardiomyopathy at high risk for adverse outcome. In this sample, with a limited number of endpoints, NT-proBNP was the strongest independent predictor for adverse outcome

Dynamic location problems with limited look-ahead

Background Among the most frequently encountered mutations in dilated cardiomyopathy (DCM) are those in the lamin A/C (LMNA) gene. Our goal was to analyze the LMNA gene in patients with DCM and/or conduction disease referred to the cardiogenetics outpatient clinic and to evaluate the prevalence of LMNA mutations and their clinical expression. Methods and Results The LMNA gene was screened in 61 index patients. Eleven mutations (including 6 novel) were identified, mainly in the subgroup of familial DCM with cardiac conduction disease (3/10 index patients) and in patients with DCM and Emery-Dreifuss, Limb-Girdle, or unclassified forms of muscular dystrophy (7/8 index patients). In addition, a mutation was identified in 1 of 4 families with only cardiac conduction disease. We did not identify any large deletions or duplications.Genotype-phenotype relationships revealed a high rate of sudden death and cardiac transplants in carriers of the p.N 195K mutation. Our study confirmed that the p.R225X mutation leads to cardiac conduction disease with late or no development of DCM, underscoring the importance of this mutation in putative familial "lone conduction disease." Nearly one third of LMNA mutation carriers had experienced a thromboembolic event. Conclusions This study highlights the role of LMNA mutations in DCM and related disorders. A severe phenotype in p.N 195K mutation carriers and preferential cardiac conduction disease in p.R225X carriers was encountered. Because of the clinical variability, including the development of associated symptoms in time, LMNA screening should be considered in patients with DCM or familial lone conduction diseas

Does Repeated Measurement of a 6-Min Walk Test Contribute to Risk Prediction in Children with Dilated Cardiomyopathy?

A single 6-min walk test (6MWT) can be used to identify children with dilated cardiomyopathy (DCM) with a high risk of death or heart transplantation. To determine if repeated 6MWT has added value in addition to a single 6MWT in predicting death or heart transplantation in children with DCM. Prospective multicenter cohort study including ambulatory DCM

Genetic Evaluation of A Nation-Wide Dutch Pediatric DCM Cohort:The Use of Genetic Testing in Risk Stratification

BACKGROUND: This study aimed to describe the current practice and results of genetic evaluation in Dutch children with dilated cardiomyopathy and to evaluate genotype-phenotype correlations that may guide prognosis. METHODS: We performed a multicenter observational study in children diagnosed with dilated cardiomyopathy, from 2010 to 2017. RESULTS: One hundred forty-four children were included. Initial diagnostic categories were idiopathic dilated cardiomyopathy in 67 children (47%), myocarditis in 23 (16%), neuromuscular in 7 (5%), familial in 18 (13%), inborn error of metabolism in 4 (3%), malformation syndrome in 2 (1%), and "other" in 23 (16%). Median follow-up time was 2.1 years [IQR 1.0-4.3]. Hundred-seven patients (74%) underwent genetic testing. We found a likely pathogenic or pathogenic variant in 38 children (36%), most often in MYH7 (n = 8). In 1 patient initially diagnosed with myocarditis, a pathogenic LMNA variant was found. During the study, 39 patients (27%) reached study endpoint (SE: all-cause death or heart transplantation). Patients with a likely pathogenic or pathogenic variant were more likely to reach SE compared with those without (hazard ratio 2.8; 95% CI 1.3-5.8, P = 0.007), while transplant-free survival was significantly lower (P = 0.006). Clinical characteristics at diagnosis did not differ between the 2 groups. CONCLUSIONS: Genetic testing is a valuable tool for predicting prognosis in children with dilated cardiomyopathy, with carriers of a likely pathogenic or pathogenic variant having a worse prognosis overall. Genetic testing should be incorporated in clinical work-up of all children with dilated cardiomyopathy regardless of presumed disease pathogenesis

A Multicenter, Long-Term Study on Arrhythmias in Children with Ebstein Anomaly

To assess the prevalence, history, and treatment of arrhythmias, in particular preexcitation and Wolff–Parkinson–White (WPW) syndrome, in patients with Ebstein anomaly (EA) during childhood and adolescence, we performed a multicenter retrospective study of all consecutive live-born patients with EA, diagnosed, and followed by pediatric cardiologists between 1980 and 2005 in The Netherlands. During a follow-up after EA diagnosis of 13 years 3 months (range: 6 days to 28 years 2 months), 16 (17%) of the 93 pediatric EA patients exhibited rhythm disturbances. Nine patients showed arrhythmic events starting as of the neonatal period. Supraventricular tachycardia was noted in 11 patients. One patient died in the neonatal period due to intractable supraventricular tachycardia resulting in heart failure and one patient died at 5 weeks of age most probably due to an arrhythmic event. The 14 surviving patients all show preexcitation, albeit 4 of them intermittently, and all have a right-sided accessory pathway location. Nine patients underwent catheter ablation of an accessory pathway. Only four patients are currently on antiarrhythmic drugs. The 17% prevalence of rhythm disturbances in pediatric EA patients, most commonly supraventricular arrhythmias, is significantly lower than in adult EA patients. Life-threatening rhythm disturbances are not frequent early in life. Symptomatic patients are well treated with radiofrequency catheter ablation