RESUMEN
BACKGROUND: Socioeconomic factors may lead to a disproportionate impact on health care usage and death among individuals with congenital heart defects (CHD) by race, ethnicity, and socioeconomic factors. How neighborhood poverty affects racial and ethnic disparities in health care usage and death among individuals with CHD across the life span is not well described. METHODS AND RESULTS: Individuals aged 1 to 64 years, with at least 1 CHD-related International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code were identified from health care encounters between January 1, 2011, and December 31, 2013, from 4 US sites. Residence was classified into lower- or higher-poverty neighborhoods on the basis of zip code tabulation area from the 2014 American Community Survey 5-year estimates. Multivariable logistic regression models, adjusting for site, sex, CHD anatomic severity, and insurance-evaluated associations between race and ethnicity, and health care usage and death, stratified by neighborhood poverty. Of 31 542 individuals, 22.2% were non-Hispanic Black and 17.0% Hispanic. In high-poverty neighborhoods, non-Hispanic Black (44.4%) and Hispanic (47.7%) individuals, respectively, were more likely to be hospitalized (adjusted odds ratio [aOR], 1.2 [95% CI, 1.1-1.3]; and aOR, 1.3 [95% CI, 1.2-1.5]) and have emergency department visits (aOR, 1.3 [95% CI, 1.2-1.5] and aOR, 1.8 [95% CI, 1.5-2.0]) compared with non-Hispanic White individuals. In high poverty neighborhoods, non-Hispanic Black individuals with CHD had 1.7 times the odds of death compared with non-Hispanic White individuals in high-poverty neighborhoods (95% CI, 1.1-2.7). Racial and ethnic disparities in health care usage were similar in low-poverty neighborhoods, but disparities in death were attenuated (aOR for non-Hispanic Black, 1.2 [95% CI=0.9-1.7]). CONCLUSIONS: Racial and ethnic disparities in health care usage were found among individuals with CHD in low- and high-poverty neighborhoods, but mortality disparities were larger in high-poverty neighborhoods. Understanding individual- and community-level social determinants of health, including access to health care, may help address racial and ethnic inequities in health care usage and death among individuals with CHD.
Asunto(s)
Disparidades en Atención de Salud , Cardiopatías Congénitas , Humanos , Cardiopatías Congénitas/etnología , Cardiopatías Congénitas/mortalidad , Cardiopatías Congénitas/terapia , Masculino , Femenino , Estados Unidos/epidemiología , Preescolar , Adolescente , Adulto , Lactante , Persona de Mediana Edad , Adulto Joven , Disparidades en Atención de Salud/etnología , Disparidades en Atención de Salud/estadística & datos numéricos , Niño , Pobreza/estadística & datos numéricos , Aceptación de la Atención de Salud/etnología , Aceptación de la Atención de Salud/estadística & datos numéricos , Negro o Afroamericano/estadística & datos numéricos , Etnicidad/estadística & datos numéricos , Características del Vecindario , Hispánicos o Latinos/estadística & datos numéricos , Características de la Residencia/estadística & datos numéricos , Población Blanca/estadística & datos numéricosRESUMEN
BACKGROUND: Racial and ethnic disparities in outcomes for children with congenital heart disease (CHD) coexist with disparities in educational, environmental, and economic opportunity. OBJECTIVES: We sought to determine the associations between childhood opportunity, race/ethnicity, and pediatric CHD surgery outcomes. METHODS: Pediatric Health Information System encounters aged <18 years from 2016 to 2022 with International Classification of Diseases-10th edition codes for CHD and cardiac surgery were linked to ZIP code-level Childhood Opportunity Index (COI), a score of neighborhood educational, environmental, and socioeconomic conditions. The associations of race/ethnicity and COI with in-hospital surgical death were modeled with generalized estimating equations and formal mediation analysis. Neonatal survival after discharge was modeled by Cox proportional hazards. RESULTS: Of 54,666 encounters at 47 centers, non-Hispanic Black (Black) (OR: 1.20; P = 0.01), Asian (OR: 1.75; P < 0.001), and Other (OR: 1.50; P < 0.001) groups had increased adjusted mortality vs non-Hispanic Whites. The lowest COI quintile had increased in-hospital mortality in unadjusted and partially adjusted models (OR: 1.29; P = 0.004), but not fully adjusted models (OR: 1.14; P = 0.13). COI partially mediated the effect of race/ethnicity on in-hospital mortality between 2.6% (P = 0.64) and 16.8% (P = 0.029), depending on model specification. In neonatal multivariable survival analysis (n = 13,987; median follow-up: 0.70 years), the lowest COI quintile had poorer survival (HR: 1.21; P = 0.04). CONCLUSIONS: Children in the lowest COI quintile are at risk for poor outcomes after CHD surgery. Disproportionally increased mortality in Black, Asian, and Other populations may be partially mediated by COI. Targeted investment in low COI neighborhoods may improve outcomes after hospital discharge. Identification of unmeasured factors to explain persistent risk attributed to race/ethnicity is an important area of future exploration.
Asunto(s)
Cardiopatías Congénitas , Determinantes Sociales de la Salud , Niño , Humanos , Recién Nacido , Asiático , Etnicidad , Cardiopatías Congénitas/epidemiología , Cardiopatías Congénitas/etnología , Cardiopatías Congénitas/mortalidad , Cardiopatías Congénitas/cirugía , Resultado del Tratamiento , Población Blanca , Negro o Afroamericano , Hispánicos o Latinos , Determinantes Sociales de la Salud/etnología , Determinantes Sociales de la Salud/estadística & datos numéricos , Estados Unidos/epidemiología , Mortalidad Hospitalaria/etnologíaRESUMEN
INTRODUCTION: Racial and ethnic disparities in resource use among children with CHD remain understudied. We sought to evaluate associations between race, ethnicity, and resource utilisation in children with CHD. MATERIALS AND METHODS: Annual data from the National Health Interview Survey were collected for years 2010-2018. Children with self-reported CHD and Non-Hispanic White race, Non-Hispanic Black race, or Hispanic ethnicity were identified. Resource use in the preceding year was identified with four measures: primary place of care visited when sick, receiving well-child checkups, number of emergency department visits, and number of office visits. Cohort characteristics were compared across racial and ethnic groups using Kruskal-Wallis and Fisher's exact tests. Multivariable logistic regression was used to determine the association of race and ethnicity with likelihood of having an emergency department visit. RESULTS: We identified 209 children for the primary analysis. Non-Hispanic Black children had significantly more emergency department visits in the prior year, with 11.1% having ≥6 emergency department visits compared to 0.7% and 5.6% of Non-Hispanic White and Hispanic children. Further, 35.2% of Hispanic children primarily received care at clinics/health centres, compared to 17% of Non-Hispanic White children and 11.1% of Non-Hispanic Black children (p = 0.03). On multivariable analysis, Black race was associated with higher odds of emergency department visit compared to White race (odds ratio = 4.19, 95% confidence interval = 1.35 to 13.04, p = 0.01). CONCLUSION: In a nationally comprehensive, contemporary cohort of children with CHD, there were some significant racial and ethnic disparities in resource utilisation. Further work is needed to consider the role of socio-economics and insurance status in perpetuating these disparities.
Asunto(s)
Servicio de Urgencia en Hospital , Utilización de Instalaciones y Servicios , Cardiopatías Congénitas , Humanos , Negro o Afroamericano/estadística & datos numéricos , Servicio de Urgencia en Hospital/estadística & datos numéricos , Etnicidad/estadística & datos numéricos , Utilización de Instalaciones y Servicios/estadística & datos numéricos , Cardiopatías Congénitas/epidemiología , Cardiopatías Congénitas/etnología , Cardiopatías Congénitas/terapia , Hispánicos o Latinos/estadística & datos numéricos , Oportunidad Relativa , Factores Raciales , Estados Unidos/epidemiología , Blanco/estadística & datos numéricosRESUMEN
Heterotaxy (HTX), a condition characterized by internal organs not being arranged as expected relative to each other and to the left-right axis, is often accompanied with congenital heart disease (CHD). The purpose was to detect the pathogenic variants in a Chinese family with HTX and CHD. A non-consanguineous Han Chinese family with HTX and CHD, and 200 unrelated healthy subjects were enlisted. Exome sequencing and Sanger sequencing were applied to identify the genetic basis of the HTX family. Compound heterozygous variants, c.3426-1G>A and c.4306C>T (p.(Arg1436Trp)), in the dynein axonemal heavy chain 11 gene (DNAH11) were identified in the proband via exome sequencing and further confirmed by Sanger sequencing. Neither c.3426-1G>A nor c.4306C>T variant in the DNAH11 gene was detected in 200 healthy controls. The DNAH11 c.3426-1G>A variant was predicted as altering the acceptor splice site and most likely affecting splicing. The DNAH11 c.4306C>T variant was predicted to be damaging, which may reduce the phenotype severity. The compound heterozygous variants, c.3426-1G>A and c.4306C>T, in the DNAH11 gene might be the pathogenic alterations resulting in HTX and CHD in this family. These findings broaden the variant spectrum of the DNAH11 gene and increase knowledge used in genetic counseling for the HTX family.
Asunto(s)
Dineínas Axonemales/genética , Predisposición Genética a la Enfermedad/genética , Cardiopatías Congénitas/genética , Síndrome de Heterotaxia/genética , Mutación Missense , Pueblo Asiatico/genética , Dineínas Axonemales/química , Preescolar , China , Femenino , Predisposición Genética a la Enfermedad/etnología , Cardiopatías Congénitas/etnología , Cardiopatías Congénitas/patología , Síndrome de Heterotaxia/etnología , Síndrome de Heterotaxia/patología , Heterocigoto , Humanos , Masculino , Linaje , Fenotipo , Conformación Proteica , Secuenciación del Exoma/métodosRESUMEN
BACKGROUND: Many individuals born with congenital heart defects (CHD) survive to adulthood. However, population estimates of CHD beyond early childhood are limited in the U.S. OBJECTIVES: To estimate the percentage of individuals aged 1-to-64 years at five U.S. sites with CHD documented at a healthcare encounter during a three-year period and describe their characteristics. METHODS: Sites conducted population-based surveillance of CHD among 1 to 10-year-olds (three sites) and 11 to 64-year-olds (all five sites) by linking healthcare data. Eligible cases resided in the population catchment areas and had one or more healthcare encounters during the surveillance period (January 1, 2011-December 31, 2013) with a CHD-related ICD-9-CM code. Site-specific population census estimates from the same age groups and time period were used to assess percentage of individuals in the catchment area with a CHD-related ICD-9-CM code documented at a healthcare encounter (hereafter referred to as CHD cases). Severe and non-severe CHD were based on an established mutually exclusive anatomic hierarchy. RESULTS: Among 42,646 CHD cases, 23.7% had severe CHD and 51.5% were male. Percentage of CHD cases among 1 to 10-year-olds, was 6.36/1,000 (range: 4.33-9.96/1,000) but varied by CHD severity [severe: 1.56/1,000 (range: 1.04-2.64/1,000); non-severe: 4.80/1,000 (range: 3.28-7.32/1,000)]. Percentage of cases across all sites in 11 to 64-year-olds was 1.47/1,000 (range: 1.02-2.18/1,000) and varied by CHD severity [severe: 0.34/1,000 (range: 0.26-0.49/1,000); non-severe: 1.13/1,000 (range: 0.76-1.69/1,000)]. Percentage of CHD cases decreased with age until 20 to 44 years and, for non-severe CHD only, increased slightly for ages 45 to 64 years. CONCLUSION: CHD cases varied by site, CHD severity, and age. These findings will inform planning for the needs of this growing population.
Asunto(s)
Cardiopatías Congénitas/epidemiología , Registro Médico Coordinado , Vigilancia de la Población , Adolescente , Adulto , Distribución por Edad , Anciano , Áreas de Influencia de Salud , Niño , Preescolar , Colorado/epidemiología , Georgia/epidemiología , Cardiopatías Congénitas/etnología , Cardiopatías Congénitas/terapia , Humanos , Lactante , Clasificación Internacional de Enfermedades , Persona de Mediana Edad , New York/epidemiología , North Carolina/epidemiología , Índice de Severidad de la Enfermedad , Distribución por Sexo , Sobrevivientes/estadística & datos numéricos , Utah/epidemiología , Adulto JovenRESUMEN
Racially disparate health outcomes exist for a multitude of populations and illnesses. It is unknown how race and ethnicity impact mortality for children with cardiomyopathy or myocarditis. This retrospective cross-sectional study employed the Kids' Inpatient Database to analyze 34,617 hospital admissions for patients ≤ 18 years old with cardiomyopathy, myocarditis, or both, without concomitant congenital heart disease. Multivariate logistic regression models investigated the impact of race/ethnicity on in-hospital mortality adjusting for age, calendar year, sex, insurance type, diagnostic category, treatment at a pediatric hospital, and non-cardiac organ dysfunction. African American race and Hispanic ethnicity were independent risk factors for mortality (African American: odds ratio (OR) 1.25, 95% confidence interval (CI) 1.01-1.53 and Hispanic: OR 1.29, 95% CI 1.03-1.60). African American race was also found to be significantly associated with the use of extracorporeal membrane oxygenation (ECMO), mortality while on ECMO, and cardiac arrest. Adjusting the regression model for ECMO and arrest attenuated the impact of African American race on mortality, suggesting that these variables may indeed play a role in explaining the impact of race on mortality for African American patients with myocardial disease. Hispanic ethnicity remained associated with higher risk of mortality despite controlling for all mechanical circulatory support and transplant (OR 1.30, 95% CI 1.04-1.63). Children of racial and ethnic minorities hospitalized with cardiomyopathy or myocarditis are more likely to die than their white counterparts, a trend that may be due at least in part to in-hospital differences in care or response to therapy.
Asunto(s)
Cardiomiopatías/mortalidad , Disparidades en Atención de Salud/etnología , Mortalidad Hospitalaria/etnología , Miocarditis/mortalidad , Adolescente , Negro o Afroamericano/estadística & datos numéricos , Cardiomiopatías/etnología , Niño , Preescolar , Estudios Transversales , Oxigenación por Membrana Extracorpórea/efectos adversos , Femenino , Paro Cardíaco/etnología , Paro Cardíaco/mortalidad , Cardiopatías Congénitas/etnología , Cardiopatías Congénitas/mortalidad , Hispánicos o Latinos/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Hospitales Pediátricos , Humanos , Lactante , Modelos Logísticos , Masculino , Miocarditis/etnología , Oportunidad Relativa , Estudios Retrospectivos , Factores de Riesgo , Estados Unidos , Población Blanca/estadística & datos numéricosRESUMEN
BACKGROUND: Social determinants of health (SDH) can substantially impact health outcomes. A systematic review, however, has never been conducted on associations of SDH with congenital heart disease (CHD) outcomes. The aim, therefore, was to conduct such a systematic review. METHODS: Seven databases were searched through May 2020 to identify articles on SDH associations with CHD. SDH examined included poverty, uninsurance, housing instability, parental educational attainment, immigration status, food insecurity, and transportation barriers. Studies were independently selected and coded by two researchers based on the PICO statement. RESULTS: The search generated 3992 citations; 88 were included in the final database. SDH were significantly associated with a lower likelihood of fetal CHD diagnosis, higher CHD incidence and prevalence, increased infant mortality, adverse post-surgical outcomes (including hospital readmission and death), decreased healthcare access (including missed appointments, no shows, and loss to follow-up), impaired neurodevelopmental outcomes (including IQ and school performance) and quality of life, and adverse outcomes for adults with CHD (including endocarditis, hospitalization, and death). CONCLUSIONS: SDH are associated with a wide range of adverse outcomes for fetuses, children, and adults with CHD. SDH screening and referral to appropriate services has the potential to improve outcomes for CHD patients across the lifespan. IMPACT: Social determinants of health (SDH) are associated with a wide range of adverse outcomes for fetuses, children, and adults with congenital heart disease (CHD). This is the first systematic review (to our knowledge) on associations of SDH with congenital heart disease CHD outcomes. SDH screening and referral to appropriate services has the potential to improve outcomes for CHD patients across the lifespan.
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Salud Infantil , Disparidades en el Estado de Salud , Disparidades en Atención de Salud , Cardiopatías Congénitas/terapia , Determinantes Sociales de la Salud , Factores Socioeconómicos , Sobrevivientes , Factores de Edad , Estado de Salud , Disparidades en Atención de Salud/etnología , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/etnología , Cardiopatías Congénitas/mortalidad , Humanos , Incidencia , Prevalencia , Pronóstico , Medición de Riesgo , Factores de Riesgo , Determinantes Sociales de la Salud/etnología , Factores de TiempoRESUMEN
A study of the prevalence rates for selected isolated non-Mendelian congenital anomalies in the Hutterite Brethren of Alberta, Canada was undertaken to further examine longitudinal data in this isolated community that was last reported in 1985 (Lowry et al., 1985), although there are numerous publications on recessive disorders (Boycott et al., 2008; Triggs-Raine et al., 2016). Cases were ascertained from the Alberta Congenital Anomaly Surveillance System for the years 1997-2016. Since our initial results showed some surprising findings in the Hutterite Brethren, such as zero cases of spina bifida, cleft lip and palate, gastroschisis, and omphalocele, and a significant excess of cases with hypospadias, we extended the study to prior years (1980-1996) for selected anomalies. For the extended study period (1980-2016), there was a significant increased prevalence of hypospadias, tetralogy of Fallot and tricuspid atresia in the Hutterite population, and although not statistically significant, zero cases of cleft lip with cleft palate, gastroschisis and omphalocele were confirmed. Further research is needed to determine the precise effects of rural environmental exposures, lifestyle factors, and genetic associations for selected multifactorial congenital anomalies.
Asunto(s)
Anomalías Congénitas/etnología , Hipospadias/etnología , Tetralogía de Fallot/etnología , Atresia Tricúspide/etnología , Alberta/epidemiología , Alberta/etnología , Fisura del Paladar/etnología , Anomalías Congénitas/genética , Consanguinidad , Exposición a Riesgos Ambientales , Femenino , Gastrosquisis/etnología , Cardiopatías Congénitas/etnología , Hernia Umbilical/etnología , Humanos , Recién Nacido , Estilo de Vida , Masculino , Defectos del Tubo Neural/etnología , Prevalencia , Población RuralRESUMEN
OBJECTIVE: Prior studies demonstrate an association between nonwhite race/ethnicity, insurance status, and mortality after pediatric congenital heart surgery. The influence of severity of illness on that association is unknown. We examined the relationship between race/ethnicity, severity of illness, and mortality in congenital cardiac surgery, and whether severity of illness is a mechanism by which nonwhite patients experience increased surgical mortality. METHODS: We performed a retrospective cohort study of children younger than age 18 years old undergoing cardiac surgery admitted to the intensive care unit (n = 40,545) between 2009 and 2016 from the Virtual Pediatric Systems (VPS, LLC, Los Angeles, Calif) database. Multivariate regression models were constructed to examine the role of severity of illness as a mediator between race/ethnicity and mortality in children undergoing cardiac surgery. RESULTS: In multivariate models examining severity of illness scores, African-American patients had statistically significant higher severity of illness scores when compared with their white counterparts. In multivariate models of intensive care unit mortality after adjustment for covariates, African-American patients had a higher odds of postoperative mortality (odds ratio, 1.40, 95% confidence interval, 1.04-1.89) when compared with white children. This increased odds of mortality was mediated through higher severity of illness, because adjustment for severity of illness removed this survival disadvantage for black patients. CONCLUSIONS: Although African-American children undergoing cardiac surgery had higher postoperative mortality, this survival difference appears to be mediated via severity of illness. Preoperative and intraoperative factors may be drivers for this survival disparity.
Asunto(s)
Procedimientos Quirúrgicos Cardíacos/métodos , Etnicidad , Disparidades en Atención de Salud/etnología , Cardiopatías Congénitas/cirugía , Grupos Raciales , Adolescente , Niño , Preescolar , Femenino , Estudios de Seguimiento , Cardiopatías Congénitas/etnología , Mortalidad Hospitalaria/tendencias , Humanos , Lactante , Recién Nacido , Masculino , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia/tendencias , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Congenital heart disease (CHD) accounts for ≈40% of deaths in US children with birth defects. Previous US data from 1999 to 2006 demonstrated an overall decrease in CHD mortality. Our study aimed to assess current trends in US mortality related to CHD from infancy to adulthood over the past 19 years and determine differences by sex and race/ethnicity. METHODS: We conducted an analysis of death certificates from 1999 to 2017 to calculate annual CHD mortality by age at death, race/ethnicity, and sex. Population estimates used as denominators in mortality rate calculations for infants were based on National Center for Health Statistics live birth data. Mortality rates in individuals ≥1 year of age used US Census Bureau bridged-race population estimates as denominators. We used joinpoint regression to characterize temporal trends in all-cause mortality, mortality resulting directly attributable to and related to CHD by age, race/ethnicity, and sex. RESULTS: There were 47.7 million deaths with 1 in 814 deaths attributable to CHD (n=58 599). Although all-cause mortality decreased 16.4% across all ages, mortality resulting from CHD declined 39.4% overall. The mean annual decrease in CHD mortality was 2.6%, with the largest decrease for those >65 years of age. The age-adjusted mortality rate decreased from 1.37 to 0.83 per 100 000. Males had higher mortality attributable to CHD than females throughout the study, although both sexes declined at a similar rate (≈40% overall), with a 3% to 4% annual decrease between 1999 and 2009, followed by a slower annual decrease of 1.4% through 2017. Mortality resulting from CHD significantly declined among all races/ethnicities studied, although disparities in mortality persisted for non-Hispanic Blacks versus non-Hispanic Whites (mean annual decrease 2.3% versus 2.6%, respectively; age-adjusted mortality rate 1.67 to 1.05 versus 1.35 to 0.80 per 100 000, respectively). CONCLUSIONS: Although overall US mortality attributable to CHD has decreased over the past 19 years, disparities in mortality persist for males in comparison with females and for non-Hispanic Blacks in comparison with non-Hispanic Whites. Determining factors that contribute to these disparities such as access to quality care, timely diagnosis, and maintenance of insurance will be important moving into the next decade.
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Negro o Afroamericano , Cardiopatías Congénitas , Longevidad , Sistema de Registros , Población Blanca , Factores de Edad , Femenino , Cardiopatías Congénitas/etnología , Cardiopatías Congénitas/mortalidad , Humanos , Masculino , Estudios Retrospectivos , Factores Sexuales , Estados Unidos/epidemiologíaRESUMEN
To assess the birth prevalence and spatial distribution of congenital heart disease (CHD) in China by conducting a complete overview and using spatial epidemiological methods. Unrestricted searches were conducted on seven electronic databases, with an end-date parameter of May 2019. Data on the birth prevalence of CHD and its subtypes were collected and combined using either the random-effect model or fixed-effect model. Subgroup sensitivity analyses were performed to explore potential heterogeneity moderators. The three-dimensional trend analysis and a visualization of CHD birth prevalence among different provinces were performed to describe the spatial distribution characteristics. Total 617 studies involving 76,961,354 births and 201,934 CHD individuals were included. Overall, total CHD birth prevalence increased continuously over time, from 0.201 in 1980-1984 to 4.905 in 2015-2019. The study on the high-income provinces, population-based monitoring model, male births, and urban regions reported a significantly higher prevalence of total CHD compared with upper-middle-income provinces, hospital-based monitoring model, female births, and rural regions, respectively. National CHD birth prevalence increased gradually from western region to eastern region, but decreased gradually from southern to northern region. Relevant heterogeneity moderators including gender, geographic region, income levels, and monitoring models have been identified by subgroup analyses. Sensitivity analysis yielded consistent results. Total CHD birth prevalence in China increases continuously in the past 40 years. Significant differences in gender, geographical regions, income levels, and monitoring models were found. In the future, population wide prospective birth defect registries covering the entire Chinese population need to determine the exact birth prevalence.
Asunto(s)
Pueblo Asiatico/estadística & datos numéricos , Cardiopatías Congénitas/epidemiología , China/epidemiología , Femenino , Cardiopatías Congénitas/etnología , Humanos , Lactante , Recién Nacido , Masculino , Embarazo , PrevalenciaRESUMEN
BACKGROUND: TAB2 is an activator of MAP 3 K7/TAK1, which is required for the IL-1 induced signal pathway. Microdeletions encompassing TAB2 have been detected in various patients with congenital heart defects (CHD), indicating that haploinsufficiency of TAB2 causes CHD. To date, seven variants within TAB2 were reported associated with CHD, only two of them are nonsense mutations. CASE PRESENTATION: Here we describe a three-generation Chinese family that included five CHD patients with heart valvular defects, such as mitral or tricuspid valves prolapse or regurgitation, and aortic valve stenosis or regurgitation. Our proband was a pregnant woman presenting with mitral, tricuspid, and aortic defects; her first child experienced sudden cardiac death at the age of 2 years. Whole-exome sequencing of the proband revealed a novel nonsense variant in TAB2 (c.C446G, p.S149X), which results in the elimination of the majority of C-terminal amino acids of TAB2, including the critical TAK1-binding domain. The variant was identified in five affected patients but not in the eight unaffected family members using Sanger sequencing and was classified as "pathogenic" according to the latest recommendation on sequence variants laid out by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. CONCLUSION: We described a family with CHD caused by a novel TAB2 nonsense mutation. Our study broadens the mutation spectrum of TAB2; to the best of our knowledge, this is the first report of a pathogenic mutation within TAB2 in a Chinese population.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Codón sin Sentido , Genes Dominantes , Cardiopatías Congénitas/genética , Adulto , Pueblo Asiatico/genética , Niño , Preescolar , China , Análisis Mutacional de ADN , Muerte Súbita Cardíaca/etiología , Femenino , Muerte Fetal/etiología , Predisposición Genética a la Enfermedad , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/etnología , Herencia , Humanos , Lactante , Masculino , Linaje , Fenotipo , Embarazo , Factores de Riesgo , Secuenciación del ExomaRESUMEN
Congenital heart defect (CHD) is one of the most common birth defects in China, while pulmonary atresia with intact ventricular septum (PA-IVS) is the life-threatening form of CHD. Numerous previous studies revealed that rare copy number variants (CNVs) play important roles in CHD, but little is known about the prevalence and role of rare CNVs in PA-IVS. In this study, we conducted a genome-wide scanning of rare CNVs in an unselected cohort consisted of 54 Chinese patients with PA-IVS and 20 patients with pulmonary atresia with ventricular septal defect (PA-VSD). CNVs were identified in 6/20 PA-VSD patients (30%), and three of these CNVs (15%) were considered potentially pathogenic. Two pathogenic CNVs occurred at a known CHD locus (22q11.2) and one likely pathogenic deletion located at 13q12.12. However, no rare CNVs were detected in patients with PA-IVS. Potentially pathogenic CNVs were more enriched in PA-VSD patients than in PA-IVS patients (p = 0.018). No rare CNVs were detected in patients with PA-IVS in our study. PA/IVS might be different from PA/VSD in terms of genetics as well as anatomy.
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Pueblo Asiatico/genética , Variaciones en el Número de Copia de ADN/genética , Cardiopatías Congénitas/genética , Defectos del Tabique Interventricular/genética , Atresia Pulmonar/genética , Niño , Preescolar , China , Femenino , Estudio de Asociación del Genoma Completo/métodos , Cardiopatías Congénitas/etnología , Humanos , Lactante , Recién Nacido , Masculino , Fenotipo , Prevalencia , Atresia Pulmonar/etnologíaRESUMEN
OBJECTIVES: Previous cross-sectional studies have demonstrated obesity rates in children with CHD and the general paediatric population. We reviewed longitudinal data to identify factors predisposing to the development of obesity in children, hypothesising that age may be an important risk factor for body mass index growth.Study designRetrospective electronic health records were reviewed in all 5-20-year-old CHD patients seen between 2011 and 2015, and in age-, sex-, and race/ethnicity-matched controls. Subjects were stratified into aged cohorts of 5-10, 11-15, and 15-20. Annualised change in body mass index percentile (BMI%) over this period was compared using paired Student's t-test. Linear regression analysis was performed with the CHD population. RESULTS: A total of 223 CHD and 223 matched controls met the inclusion criteria for analysis. Prevalence of combined overweight/obesity did not differ significantly between the CHD cohort (24.6-25.8%) and matched controls (23.3-29.1%). Univariate analysis demonstrated a significant difference of BMI% change in the age cohort of 5-10 (CHD +4.1%/year, control +1.7%/year, p=0.04), in male sex (CHD +1.8%/year, control -0.3%/year, p=0.01), and status-post surgery (CHD 2.03%/year versus control 0.37%, p=0.02). Linear regression analysis within the CHD subgroup demonstrated that age 5-10 years (+4.80%/year, p<0.001) and status-post surgery (+3.11%/year, p=0.013) were associated with increased BMI% growth. CONCLUSIONS: Prevalence rates of overweight/obesity did not differ between children with CHD and general paediatric population over a 5-year period. Longitudinal data suggest that CHD patients in the age cohort 5-10 and status-post surgery may be at increased risk of BMI% growth relative to peers with structurally normal hearts.
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Etnicidad , Cardiopatías Congénitas/complicaciones , Obesidad/etiología , Medición de Riesgo/métodos , Adolescente , Índice de Masa Corporal , Niño , Preescolar , Estudios Transversales , Femenino , Cardiopatías Congénitas/etnología , Humanos , Masculino , Obesidad/etnología , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Estados Unidos/epidemiología , Adulto JovenRESUMEN
OBJECTIVE: The current study aims to identify the rates of lapses in care and loss to follow-up before age one through age five for white and nonwhite congenital heart disease (CHD) survivors. Nonwhite CHD survivors were hypothesized to experience an earlier lapse in care and be lost to follow-up than whites. DESIGN: Patients were from a large pediatric hospital and had (1) at least one outpatient cardiology clinic visit or cardiac surgery visit before the age of one and (2) a diagnosis of moderate or complex structural CHD. Cardiology outpatient utilization rates were tracked from before age one through age five. Lapse in follow-up was defined as not having at least one outpatient cardiology visit per year, and loss to follow-up was not returning after a lapse in care by age five. Race was categorized as white and nonwhite. Covariates included sex, insurance type, noncardiology inpatient and outpatient hospital utilization, and CHD severity. RESULTS: The sample included 1034 patients. Overall, 75.7% experienced a lapse in care with only 41.6% of those returning by age five. Nonwhites experienced lapses in care at younger ages than whites. Nonwhites had a 53% increased risk of lapse in care. Medicaid patients and those with moderate CHD diagnoses also had an increased risk for lapse in care. CONCLUSIONS: Lapse in care appears prevalent among CHD survivors by age five, with nonwhites demonstrating elevated risk. Future multisite prospective studies should include the assessment of parental knowledge, barriers to accessing care, and satisfaction with care.
Asunto(s)
Cardiopatías Congénitas/etnología , Hospitales Pediátricos , Grupos Raciales , Sobrevivientes/estadística & datos numéricos , Factores de Edad , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Ohio/epidemiología , Prevalencia , Estudios Retrospectivos , Encuestas y CuestionariosRESUMEN
BACKGROUND: Congenital heart disease (CHD) survivors have an elevated risk for obesity-related comorbidities, but little is known about racial differences in obesity rates for this population. OBJECTIVE: The authors aimed to compare rates of obesity in CHD survivors to national estimates using National Health and Nutrition Examination Assessment Survey (NHANES) and to characterize racial disparities in obesity among CHD survivors across age ranges. METHODS: Retrospective chart review included 4496 CHD survivors (4050 white and 446 black) with a range of lesion severities from a pediatric and an adult medical center. RESULTS: White children with CHD had a higher prevalence of obesity compared with NHANES estimates. In contrast, white young adults with CHD had a lower prevalence of obesity compared with NHANES. Blacks with CHD had a 58% increased risk of obesity in young adulthood and a 33% increased risk in late adulthood compared with whites with CHD. CONCLUSIONS: Obesity interventions are needed among CHD survivors across the lifespan, particularly among adult non-Hispanic blacks.
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Negro o Afroamericano/estadística & datos numéricos , Cardiopatías Congénitas/etnología , Obesidad Infantil/etnología , Sobrevivientes/estadística & datos numéricos , Población Blanca/estadística & datos numéricos , Adolescente , Niño , Femenino , Cardiopatías Congénitas/complicaciones , Humanos , Masculino , Obesidad Infantil/etiología , Prevalencia , Estados UnidosRESUMEN
BACKGROUND: Tbx2 plays a critical role in determining fates of cardiomyocytes. Little is known about the contribution of TBX2 3' untranslated region (UTR) variants to the risk of congenital heart defect (CHD). Thus, we aimed to determine the association of single-nucleotide polymorphisms (SNPs) in TBX2 3' UTR with CHD susceptibility. METHODS: We recruited 1285 controls and 1241 CHD children from China. SNPs identification and genotyping were detected using Sanger Sequencing and SNaPshot. Stratified analysis was conducted to explore the association between rs59382073 polymorphism and CHD subtypes. Functional analyses were performed by luciferase assays in HEK-293T and H9c2 cells. RESULTS: Among five TBX2 3'UTR variants identified, rs59382073 minor allele T carriers had a 1.89-fold increased CHD risk compared to GG genotype (95% CI = 1.48-2.46, P = 4.48 × 10-7). The most probable subtypes were right ventricular outflow tract obstruction, conotruncal, and septal defect. G to T variation decreased luciferase activity in cells. This discrepancy was exaggerated by miR-3940 and miR-708, while their corresponding inhibitors eliminated it. CONCLUSION: T allele of rs59382073 in TBX2 3'UTR contributed to greater CHD risk in the Han Chinese population. G to T variation created binding sites for miR-3940 and miR-708 to inhibit gene expression.
Asunto(s)
Predisposición Genética a la Enfermedad , Cardiopatías Congénitas/genética , Polimorfismo de Nucleótido Simple , Proteínas de Dominio T Box/genética , Regiones no Traducidas 3' , Alelos , Animales , Pueblo Asiatico , Sitios de Unión , Estudios de Casos y Controles , Niño , China/etnología , Ecocardiografía , Femenino , Regulación de la Expresión Génica , Genotipo , Células HEK293 , Cardiopatías Congénitas/etnología , Ventrículos Cardíacos , Humanos , Masculino , MicroARNs/genética , Fenotipo , Plásmidos/metabolismo , Ratas , Medición de RiesgoRESUMEN
BACKGROUND: Microtia is a congenital anomaly of the external ear that can appear in isolation or in association with other congenital anomalies. In this study, the authors identify the prevalence and phenotypes of associated congenital malformations in patients with microtia in a Chinese specialty clinic population. METHODS: Data were collected from 672 patients seen between December of 2014 and February of 2016 in the Department of Auricular Reconstruction at the Plastic Surgery Hospital of Peking Union Medical College. All patients were examined by trained clinicians and classified into one of three grades of microtia. Co-occurring congenital anomalies were detected and recorded. RESULTS: The majority of study participants were male patients (72 percent), and most participants had unilateral microtia (93 percent, 68 percent of whom had right-side microtia). Two hundred ninety-three patients (44 percent) had one or more associated anomalies. The most commonly occurring comorbid malformations were those of the ear, face, and neck (40 percent of all associated malformations); musculoskeletal system (35 percent); and cardiovascular system (11 percent). CONCLUSIONS: These data represent the first detailed and thematic study of microtia and associated congenital anomalies in a Chinese clinical population. Substantial clinical heterogeneity was observed, and the prevalence of comorbid congenital malformations was high. Future studies investigating congenital anomalies associated with microtia are needed to improve understanding of its cause.