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Birth Prevalence of Congenital Heart Disease Worldwide
Abstract
Congenital heart disease (CHD) accounts for nearly one-third of all major congenital anomalies. CHD birth prevalence worldwide and over time is suggested to vary; however, a complete overview is missing. This systematic review included 114 papers, comprising a total study population of 24,091,867 live births with CHD identified in 164,396 individuals. Birth prevalence of total CHD and the 8 most common subtypes were pooled in 5-year time periods since 1930 and in continent and income groups since 1970 using the inverse variance method. Reported total CHD birth prevalence increased substantially over time, from 0.6 per 1,000 live births (95% confidence interval [CI]: 0.4 to 0.8) in 1930 to 1934 to 9.1 per 1,000 live births (95% CI: 9.0 to 9.2) after 1995. Over the last 15 years, stabilization occurred, corresponding to 1.35 million newborns with CHD every year. Significant geographical differences were found. Asia reported the highest CHD birth prevalence, with 9.3 per 1,000 live births (95% CI: 8.9 to 9.7), with relatively more pulmonary outflow obstructions and fewer left ventricular outflow tract obstructions. Reported total CHD birth prevalence in Europe was significantly higher than in North America (8.2 per 1,000 live births [95% CI: 8.1 to 8.3] vs. 6.9 per 1,000 live births [95% CI: 6.7 to 7.1]; p < 0.001). Access to health care is still limited in many parts of the world, as are diagnostic facilities, probably accounting for differences in reported birth prevalence between high- and low-income countries. Observed differences may also be of genetic, environmental, socioeconomical, or ethnic origin, and there needs to be further investigation to tailor the management of this global health problem.
... 2 The current literature shows that the burden of the disease is on the rise globally. [3][4][5] This could be due predominantly to improved diagnostic imaging coupled with increased survival rather than notable increases in the true incidence of CHD. However, little is known about the burden of CHD in the pediatric population in Africa. ...
... Discrepancies were resolved by team discussions, similar to previous studies. [3][4][5] All relevant peer-reviewed observational studies conducted in Africa and reporting the prevalence of CHD in children from birth to 18 years, or at least providing the data to compute the prevalence, were included. Articles reporting the prevalence of acquired heart disease with coincidental and isolated findings on CHD were considered. ...
... The upward rise in our study occurring after 2001 is similar to the reported global trend observed after 1995. [3][4][5] The six-year lag could signify the buildup of accessible echocardiography services across Africa, resulting in increased research activities. This could more likely explain the upward trend we observed in the population-based prevalence over the study period, rather than representing a true prevalence increase. ...
Background
There are limited population-based studies on congenital heart disease (CHD) in the pediatric population in Africa. Technological advancements in diagnostic tools have resulted in multiple echocardiographic studies in hospital settings. We aimed to determine the prevalence of CHD in both settings (population-based and hospital based) followed by comparing the two estimates for a difference.
Methods
We systematically searched PubMed, Google Scholar, African Journals Online, and African Index Medicus for eligible studies from 1992 through 2022. We performed a meta-analysis using the random-effects model.
Results
We selected 42 studies; 10 population studies with 1,011,163 participants, and 32 hospital-based studies with 605,268 patients for the analyses. The population and hospital-based prevalence were 5.12 versus 12.63 per 1,000 population of children ( P = .007). Ventricular septal defect was the most common type of CHD in both settings (0.61 vs 1.88 per 1,000), followed by atrial septal defect (0.26 vs 0.68 per 1,000). Tetralogy of Fallot was the most common cyanotic heart lesion in both settings (0.08 vs 0.52 per 1,000).
Conclusions
The population-based prevalence of CHD was significantly lower than the hospital-based prevalence (5.12 vs 12.63 per 1,000 population of children). Juxtaposing these two prevalence estimates against each other can be a reasonable alternative to quantifying the contemporary burden of CHD in the pediatric population of Africa. Moving forward, efforts should bolster awareness of CHD in Africa, and further advocacy for children with CHD should be a priority on the continent.
... Los defectos cardíacos son las malformaciones congénitas mayores más frecuentes [11][12][13] , presentes en un 3-4% de los RN en Chile 8,9 . Las CC están dentro de las principales causas de muerte por malformaciones congénitas 14,15 , siendo un 20% de las muertes neonatales y casi un 50% de la mortalidad infantil 15,16 . ...
... Los defectos cardíacos son las malformaciones congénitas mayores más frecuentes [11][12][13] , presentes en un 3-4% de los RN en Chile 8,9 . Las CC están dentro de las principales causas de muerte por malformaciones congénitas 14,15 , siendo un 20% de las muertes neonatales y casi un 50% de la mortalidad infantil 15,16 . ...
... Las CC presentan diferencias sociodemográficas y determinantes sociales en cuanto a su incidencia 14 . "La epidemiología y contexto social juegan un rol crucial en determinar la carga de una enfermedad y modular los posibles resultados, mientras que el diagnóstico y tratamiento siguen siendo principalmente dependientes de los recursos" 15 19,26 . Es importante recalcar que el diagnóstico se puede realizar de manera antenatal en la ecografía fetal después de las 16 semanas en algunos casos 27,28 , permitiendo un tratamiento precoz y mejor pronóstico 16 . ...
Introducción: Las cardiopatías congénitas corresponden a defectos estructurales del corazón y/o válvulas cardíacas y/o grandes vasos secundarios a errores en la embriogénesis cardíaca que están presentes al nacer. El diagnóstico puede ser clínico e imagenológico al momento del nacimiento o antenatal mediante la ecografía fetal. El pronóstico está determinado por las condiciones al momento de la cirugía y por la existencia de malformaciones asociadas. Objetivo: Evaluar las medidas de prevención que existen a nivel nacional para identificar oportunidades para su mejoría. Metodología: Se realizó una revisión bibliográfica en la plataforma SciElo y en documentos del MINSAL. Se seleccionaron 8 artículos que se utilizaron para esta revisión. Resultado: La prevención primaria se basa en identificar factores de riesgo, vacunación contra la Rubéola y suplementación. A nivel secundario existe principalmente ecografía de pesquisa y seguimiento ante el diagnóstico mediante el GES. Finalmente, la prevención terciaria consiste en el tratamiento sintomático y eventual resolución quirúrgica. Discusión: Chile aún tiene espacio para crecer en métodos de prevención en todos los niveles. A nivel primario es necesario aumentar la cobertura de educación y control prenatal. A nivel secundario es imperativo formar a los profesionales de salud para implementar estudios ecográficos tanto antenatales como postnatales. Y en prevención terciaria se pueden implementar medidas de rehabilitación y tratamientos paliativos Conclusión: La pesquisa y tratamiento precoz mediante métodos de tamizaje durante el período prenatal permitiría aumentar la sobrevida y disminuir la necesidad de cirugía.
... A disturbance in this process may result in an anomaly, i.e., congenital heart defect (CHD). CHD is one of the most common congenital anomalies in children with an incidence of 7-8 cases per 1000 live births and the etiology of the condition is still usually unknown (34). ...
... fulfilling study inclusion criteria, and willing to participate in the ORALPEDHEART-study. The ultimate strengths of this thesis include the rigid inclusion criteria of a CHD child study population at high risk of poor oral health, a national population-based prospective study sample, and a randomized controlled trial study design.In total, 189,974 children were born in Finland between in 2017-2020(134).As the prevalence of CHD is 7-8 cases per 1,000 live born per year, the estimated number of CHD children born during the four-year ORALPEDHEART-sample recruitment period is approximately 1,400(34).Among these CHD children, 91 children were from Finnish-speaking families and represent CHD children with the most severe CHD forms that are included in endocarditis prophylaxis guidelines or present with a syndrome and CHD requiring an intervention.The rigid inclusion criteria of the children with CHD allow us to examine the group of children that will benefit the most from the oral health promotion intervention from a cardiovascular point of view. A national population-based setting combined with a randomized controlled study design increases the strength of this thesis and the validity of the study results.We attempted to minimize families lost to follow up during this longitudinal study and managed to achieve appropriate response rates in all phases of the data collection. ...
Congenital heart disease (CHD) is one of the most common congenital
anomalies in children with an incidence of 7-8 per 1000 live births.
Maintaining optimal oral health behavior in children with CHD is important
in managing the risk for developing poor oral health (e.g., dental caries) that
might predispose to infective endocarditis (IE). Children with CHD are prone
to dental caries due to factors associated with severe systemic disease.
Maintaining favourable oral health behaviors including regular
toothbrushing, use of fluoride toothpaste, reasonable consumption of sugar
and regular dental care visit are important evidence-based preventive
measures in achieving optimal oral health long term.
Caregivers are responsible for maintaining oral health behavior of young
children. The benefits of parental support can potentially be far-reaching,
since adapted behavior in early childhood often persist into adulthood. Due to
significant disease burden in families with major CHD, and the importance of
oral health behavior for the overall health of the CHD child, it would be
essential to provide targeted oral health care support for early prevention of
dental caries.
The general aim of this thesis was to develop, assess feasibility, and evaluate
the impact of a dental hygienist led oral health promotion intervention
including counselling and support provided during a 24-month period from
early age (children <12 months of age) to families with major CHD children,
or any surgically operated CHD combined with a syndrome. To achieve these
aims four studies (I-IV) were conducted.
In study I, the prevalence of caries between children with CHD and healthy
children were evaluated. Nine studies were included in the systematic
literature review, of which seven indicated a higher prevalence of caries in
children with CHD compared to healthy children. Out of the seven studies,
three showed statistically significantly more caries in children with CHD
compared to healthy children. According to two studies, children with heart
conditions had less caries compared to healthy children, but the difference was
not statistically significant.
In study II, the feasibility of a novel custom developed oral health promotion
intervention was studied through interviews with nine participating parents.
Four main categories and 14 subcategories were identified to describe the
parental perceptions and experiences of the intervention. The main categories
were timing of first intervention contact, effortlessness of intervention
process, individuality of support, and relevancy of support.
In study III, the national situation of oral health behavior in children with
major CHD born in Finland was assessed with parental questionnaires in a
prospective population-based sample of 27 children with major CHD in
comparison with 50 healthy children child at 24 months of age. Toothbrushing
habits in children with CHD were poorer than in healthy children and children
with CHD more often drank other than water between meals compared to
healthy children.
In study IV, the impact of the developed oral health promotion intervention
was evaluated at child age 24-months in a prospective randomized controlled
trial comparing parental questionnaire data between 1:1 randomly assigned
CHD intervention (n=27) and CHD control (n=30) groups, and a parallel
passive healthy children comparison group (n=50).
After early oral health counselling, brushing twice a day, the use of fluoride
toothpaste, the use of an electric toothbrush, and water as the drink between
meals was increased in children with CHD in the intervention group. In both
studies (III & IV) parental and child oral health behavior associations were
assessed. In both studies parental toothbrushing predicted child
toothbrushing twice a day.
In conclusion, children with CHD experience higher caries prevalence than
healthy children. Parents found the oral health counselling provided at an
early stage to be important. Children with CHD in Finland seems to experience
poorer oral health behavior compared to healthy children. Oral health
behavior could be improved by oral health promotion intervention. The results
of this thesis could also be used to improve the oral health behavior of other
high caries risk patients.
... CHD accounts for nearly one-third of all major congenital anomalies. It is one of the most prevalent congenital anomalies, affecting approximately 8 out of every 1,000 live births globally, though incidence varies by region and time [14]. With advancements in medical diagnostics techniques and treatment levels, survival rates for CHD patients have improved. ...
Pulmonary arterial hypertension (PAH) is a complex and progressive disease characterized by elevated pulmonary artery pressure and vascular remodeling. Recent studies have underscored the pivotal role of metabolic dysregulation and epigenetic modifications in the pathogenesis of PAH. Lactate, a byproduct of glycolysis, is now recognized as a key molecule that links cellular metabolism with activity regulation. Recent findings indicate that, in addition to altered glycolytic activity and dysregulated. Lactate homeostasis and lactylation—a novel epigenetic modification—also play a significant role in the development of PAH. This review synthesizes current knowledge regarding the relationship between altered glycolytic activity and PAH, with a particular focus on the cumulative effects of lactate in pulmonary vascular cells. Furthermore, lactylation, an emerging epigenetic modification, is discussed in the context of PAH. By elucidating the complex interplay between lactate metabolism and lactylation in PAH, this review aims to provide insights into potential therapeutic targets. Understanding these metabolic pathways may lead to innovative strategies for managing PAH and improving patient outcomes. Future research should focus on the underlying mechanisms through which lactylation influences the pathophysiology of PAH, thereby aiding in the development of targeted interventions.
... It 's essential to consider the generalizability of the studies, as most were developed and validated using Asian populations, with only one study evaluating AI performance in American populations. Evidence has shown that Asians have the highest prevalence of CHD, so more datasets based on other ethnicities are necessary to ensure the study's generalizability (43). ...
Background
Congenital heart disease (CHD) is a major contributor to morbidity and infant mortality and imposes the highest burden on global healthcare costs. Early diagnosis and prompt treatment of CHD contribute to enhanced neonatal outcomes and survival rates; however, there is a shortage of proficient examiners in remote regions. Artificial intelligence (AI)-powered ultrasound provides a potential solution to improve the diagnostic accuracy of fetal CHD screening.
Methods
A literature search was conducted across seven databases for systematic review. Articles were retrieved based on PRISMA Flow 2020 and inclusion and exclusion criteria. Eligible diagnostic data were further meta-analyzed, and the risk of bias was tested using Quality Assessment of Diagnostic Accuracy Studies—Artificial Intelligence.
Findings
A total of 374 studies were screened for eligibility, but only 9 studies were included. Most studies utilized deep learning models using either ultrasound or echocardiographic images. Overall, the AI models performed exceptionally well in accurately identifying normal and abnormal ultrasound images. A meta-analysis of these nine studies on CHD diagnosis resulted in a pooled sensitivity of 0.89 (0.81–0.94), a specificity of 0.91 (0.87–0.94), and an area under the curve of 0.952 using a random-effects model.
Conclusion
Although several limitations must be addressed before AI models can be implemented in clinical practice, AI has shown promising results in CHD diagnosis. Nevertheless, prospective studies with bigger datasets and more inclusive populations are needed to compare AI algorithms to conventional methods.
Systematic Review Registration
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023461738, PROSPERO (CRD42023461738).
... The advancement of medical imaging technology has significantly improved the visualization and diagnosis of medical conditions, even during the fetal stage, using various modalities. ECG is a widely used non-invasive method that records the heart's electrical activity as a voltage-time graph, enabling the detection of abnormalities through pattern analysis and time intervals between peaks [1], [2]. Phonocardiography (PCG) captures heart sounds through the sound of blood flowing from the atrium to the ventricles through the tri and bi-cuspid valve simultaneously which is denoted as S1 and sound S2 records the closing of aortic valve and pulmonary valve which are together called the semilunar valves. ...
Pediatric cardiac disorders include an extensive range of heart conditions in infants, children and carried over to adolescents in certain cases. These disorders may be congenital or acquired and can vary in impacting the life of the pediatric subject which requires complex surgical procedures and certain cases that do not require medical intervention. Congenital heart disease (CHD) is present during birth and acquired cardiac diseases are developed after birth predominantly due to autoimmune responses or infections. Various acquisition techniques help in visualizing the heart, identify disorders and help the physicians to plan for operative procedures. Pediatric Cardiac Screening is one of the crucial techniques to record cardiac activity which has difficulties in acquisition as children tend to move during the procedure. The data obtained from these modalities may suffer from various artifacts which makes the diagnosis difficult for the clinicians. To make the diagnosis easier and artifact free, artificial intelligence plays a vital role. Artificial Intelligence (AI)-based techniques from traditional machine learning (ML) to deep learning (DL) techniques for classification and segmentation of pediatric cardiac signals and images are systematically reviewed. DL based studies have become a choice of research in pediatric healthcare. Support Vector Machines with linear kernels are the most commonly used ML based classifiers in the reviewed papers. DL methods use Convolutional Neural Networks (CNN) as the primary classifier and U-Net architectures are preferred for segmentation studies in the reviewed papers. There are a very few surveys available to present the diagnostics related to pediatric cardiac disorders and this paper tries to bring out the challenges along with the traditional machine learning and emerging deep learning techniques implemented in classification and segmentation of the pediatric cardiac disorders.
... This can be seen in Fig. 2. It constitutes 10% of congenital heart disease and is the most common cyanotic congenital heart disease. It has a prevalence of 340-421 affected per million live births worldwide [7,8]. ...
Since the first identification of Tetralogy of Fallot in 1671, consisting of a combination of anatomical defects including biventricular origin of the aorta, maligned ventricular septal defect, overriding aorta, and narrowing or atresia of the pulmonary outflow tract. The first successful operation consisted of a shunt between the left subclavian artery and pulmonary artery. Following this palliative procedure, complete repair is performed once the patient reaches indicative criteria. Since the first attempts at surgical palliation and repair, techniques and outcomes have improved drastically. Definitive repair of Tetralogy of Fallot consists of a multi-patch closure of any Ventricular Septal Defect along with clearance of any muscular obstructions of the Right Ventricular Outflow Tract and reconstruction of the outflow tract. Current results of Tetralogy of Fallot palliation yield excellent long and short-term results with 5-year freedom from reintervention of 90%. The iterative improvement of repair techniques has greatly reduced intraoperative and postoperative complications. Future innovations such as increased use of percutaneous repair methods and additional data on the benefits of primary repair as opposed to staged palliation will continue to improve patient outcomes.
... Tetralogy of Fallot (ToF) is a common form of cyanotic congenital heart disease (CHD) with an estimated birth prevalence of 0.34 per 1000 live-births [1]. The first successful repair was performed by Lillehei in 1954 [2]. ...
... Congenital heart disease (CHD) is a defect of the heart caused by abnormalities in the process of its development. It is one of the most common birth defects characterized by a wide range of structural deformities of the heart and great vessels, affecting 10 per 1000 (~ 1%) neonates worldwide, along with 10% of stillbirths [1][2][3][4]. The complex multifactorial etiology of CHD presents a major challenge towards understanding its clear pathological mechanism. ...
Congenital heart disease (CHD) is a prevalent condition characterized by defective heart development, causing premature death and stillbirths among infants. Genome-wide association studies (GWASs) have provided insights into the role of genetic variants in CHD pathogenesis through the identification of a comprehensive set of single-nucleotide polymorphisms (SNPs). Notably, 90–95% of these variants reside in the noncoding genome, complicating the understanding of their underlying mechanisms. Here, we developed a systematic computational pipeline for the identification and analysis of CHD-associated SNPs spanning both coding and noncoding regions of the genome. Initially, we curated a thorough dataset of SNPs from GWAS-catalog and ClinVar database and filtered them based on CHD-related traits. Subsequently, these CHD-SNPs were annotated and categorized into noncoding and coding regions based on their location. To study the functional implications of noncoding CHD-SNPs, we cross-validated them with enhancer-specific histone modification marks from developing human heart across 9 Carnegie stages and identified potential cardiac enhancers. This approach led to the identification of 2,056 CHD-associated putative enhancers (CHD-enhancers), 38.9% of them overlapping with known enhancers catalogued in human enhancer disease database. We identified heart-related transcription factor binding sites within these CHD-enhancers, offering insights into the impact of SNPs on TF binding. Conservation analysis further revealed that many of these CHD-enhancers were highly conserved across vertebrates, suggesting their evolutionary significance. Utilizing heart-specific expression quantitative trait loci data, we further identified a subset of 63 CHD-SNPs with regulatory potential distributed across various cardiac tissues. Concurrently, coding CHD-SNPs were represented as a protein interaction network and its subsequent binding energy analysis focused on a pair of proteins within this network, pinpointed a deleterious coding CHD-SNP, rs770030288, located in C2 domain of MYBPC3 protein. Overall, our findings demonstrate that SNPs have the potential to disrupt gene regulatory systems, either by affecting enhancer sequences or modulating protein-protein interactions, which can lead to abnormal developmental processes contributing to CHD pathogenesis.
... Congenital heart diseases (CHD), also known as congenital heart anomalies and congenital heart defects, are defects in the structure of the heart or major vessels that are present at birth. The global incidence of congenital cardiovascular defects is approximately eight per 1,000 newborn live births (Van Der Linde et al., 2011), with more recent studies suggesting an increases to as high as 9.5 per 1,000 live births (Liu et al., 2019). CHD remains a major cause of infant mortality; it is about 40% in the U.S. (Lopez et al., 2020), and the incidence of CHD is 25 per 1000 live births at Jordanian Children Born in Jordan (Khasawneh et al., 2020). ...
Background: Congenital heart diseases (CHDs) are known as congenital heart defects or anomalies. It refers to structural defects in the heart or major vessels present at birth. CHD is the most prevalent type of birth defect worldwide. The etiology of CHD is complex and multifactorial, involving both genetic and environmental factors. Understating these risk factors is essential for prenatal diagnosis, primary prevention, and decreasing preventable new cases. Aim of Study: This study aimed to assess the most common CHDs and the maternal associated factors in the West Bank, Palestine. Method: A cross-sectional descriptive survey was conducted at three major hospitals in the West Bank between August and November 2021 that treat congenital heart diseases (CHDs); Al-Makased Islamic Hospital, Palestine Medical Complex Hospital, and Arab Women Union Society-Nablus. Data were collected through face-to-face interviews using a structured questionnaire. Result: Data analysis of 108 cases revealed that the most common CHD is atrial septal defect (ASD), accounting for 25.9% of cases. Most mothers were between 20-30 years (52.8%). Among the children, 57 (52.8%) were male. Most children were born between 36-38 weeks of gestation age (34.3%) and had a normal birth weight (54.6%). In addition, 58.3% of families did not have a history of CHD among relatives. There is a significant association was found between CHD diagnosis and Birth weight, a family history of CHD, maternal BMI, periconceptional smoking, and commitment to folic acid intake. Conclusion: The findings of this study underscore the need for enhanced health policies that prioritize premarital and prenatal counseling, along with proper management of maternal health conditions. Increasing awareness among women of reproductive age about key risk factors; such as family history of CHD, maternal BMI, smoking, and folic acid intake, that they can play a critical role in reducing the incidence of CHD in newborns. Effective preventive strategies and targeted education are vital to mitigating the risk factors associated with congenital heart disease in the West Bank.
... C ongenital heart disease (CHD) encompasses a spectrum of structural malformations or functional abnormalities of the heart that are present at birth, although diagnosis may occur later in life [1]. The severity of these cardiac defects can range from undetectable anomalies to life-threatening conditions [2]. Global estimates suggest a CHD incidence of approximately 8 per 1,000 live births [1,3], with recent studies potentially revising this figure upwards to 9.5 per 1,000 [4]. ...
Background: Congenital heart disease (CHD) represents the most common and lethal birth defect affecting newborns. This study aimed to characterize the echocardiographic profile of CHDs, along with their prevalence and associated risk factors in CHD patients. Materials and Methods: This cross‐sectional, analytical study was conducted on CHD patients referred to the major pediatric hospital affiliated with Urmia University of Medical Sciences between March 2022 and October 2023. They were selected by convenience sampling method. The collected data, including mothers' parity, prior diagnoses of heart disease, hypertension, diabetes, thyroid disorders, COVID-19 infection during pregnancy, prior surgical procedures, use of complementary medicine during gestation, medication history, and mode of delivery. Additionally, child-related characteristics were investigated, including age, gender, co-existing congenital cardiovascular disease, neonatal intensive care unit (NICU) admission history, and echocardiographic findings. Specifically, the study focused on abnormalities in left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF). Data analysis was done using SPSS software version 22.0. Results: Of 293 CHD children, 59.72% were male and 40.27% were female. Overall, 132 (45%) children were below one year of age. Among echocardiography profile, Patent Foramen Ovale (PFO) constituted 65 cases accounting for 22.1% of all CHD cases and Atrial septal defect (ASD) was the second most common CHD accounting for 16.3% of all CHD cases. Mother's infection with Covid-19 during pregnancy (P<0.001), type of delivery (P=0.015), and patient's NICU hospitalization (P=0.010) was statistically significant among the patients with normal and abnormal echocardiography. Conclusion: This study reveals a significant prevalence of Patent Foramen Ovale (PFO) and Atrial Septal Defect (ASD) among patients with congenital heart disease (CHD), highlighting the crucial role of early echocardiographic screening in this group. It also suggests a potential link between maternal COVID-19 infection during pregnancy, the method of delivery, and abnormal echocardiographic findings in CHD patients.
... The incidence of CHD is estimated at 8 per 1000 live births in India [3] , while in the United States, CHD affects approximately 1% of live births [3,4] . In Europe, the total prevalence is 8 per 1000 births, with 7.2 per 1000 being live births [5,6] . Prevalence varies widely, ranging from 1.3-50.89 ...
... Congenital heart disease (CHD) encompasses a spectrum of inborn heart defects that are the most common congenital anomalies worldwide, affecting approximately 1 in 100 newborns 1,2 . The majority of children with CHD require surgical intervention in early life 2 . ...
Congenital heart disease (CHD) is the most common birth defect in newborns, often requiring cardiac surgery with concomitant thymectomy that is known to increase disease susceptibility later in life. Studies of γδ T cells, which are one of the dominant T cells in the early fetal human thymus, are rare. Here, we provide a comprehensive analysis of the γδ T cell compartment via flow cytometry and next-generation sequencing in children and infants with CHD, who underwent cardiac surgery shortly after birth. A perturbation of the γδ T cell repertoire is evident, and Vδ1 T cell numbers are reduced. However, those cells that are present, do retain cytotoxicity. In contrast, GZMA+CD28+CD161hi innate effector Vγ9Vδ2 T cells are found in higher proportions. TCR-seq identifies an increase in TRDJ3+ γδ T cell clones in children with CHD, but not in a confirmatory group of neonates prior to CHD surgery, which overall points to a persistence of fetal-derived effector γδ T cells in children with CHD.
... Congenital heart disease (CHD) is a birth defect affecting 1-1.2 % of live born infants [1][2][3]. Several studies highlighted the role of prenatal and early neonatal CHD diagnosis in optimizing neonatal survival by allowing presurgical stabilization [4][5][6][7][8][9][10]. Current literature focuses on outcomes of neonates with prenatally diagnosed major CHD delivered at academic medical centers with level IV neonatal intensive care units (NICU) and onsite pediatric cardiac surgery capabilities [11,12]. ...
Objectives
Determine obstetrical and neonatal outcomes in neonates with major congenital heart disease (CHD) delivered at a level IV neonatal intensive care units (NICU) center lacking onsite pediatric cardiac surgery.
Methods
A 10-year retrospective review of all neonates admitted to our level IV NICU, with CHD between January 1st, 2011 and December 31st, 2021. Births and NICU charts were cross queried with those from our perinatal center which include pediatric cardiology records. Terminations and stillbirths were excluded.
Results
A total of 285 neonates with major CHD and 78 with minor defects were included. In the major CHD group, 82.8 % had an isolated cardiac anomaly and 17.2 % had an extracardiac anomaly. Type of extracardiac anomaly had no impact on neonatal survival. Prenatal diagnosis of aneuploidy did not impact survival in major CHD. Truncus arteriosus had the highest NICU mortality at 34.0 % followed by hypoplastic left heart syndrome (HLHS) at 31.6 %. Double outlet right ventricle with transposition of the great vessels and interrupted aortic arch (both types) had a 25 % mortality. Neonates with truncus arteriosus and total anomalous pulmonary venous returns were likely to have 5-min Apgar score<7. Transfer rate of neonates with major CHD for cardiac surgery was 58.6 %. Of those 81.5 % were discharged home, 14.3 % expired before discharge, and 1 % were transferred elsewhere post-operatively for higher level of care.
Conclusions
Neonates with major CHD can deliver safely at a level IV NICU lacking onsite pediatric cardiac surgery. Our neonatal mortality was high for HLHS and truncus arteriosus, however comparable to other centers with proximate pediatric cardiac surgery.
Advances in fetal cardiac ultrasound technologies and refinements in cardiac catheterization techniques have made fetal cardiac intervention a reasonable option for fetuses with cardiac abnormalities such as fetal aortic stenosis and fetal hypoplastic left heart syndrome. These procedures — fetal aortic balloon valvuloplasty and fetal atrial stenting — are performed on the physical body of the mother for the benefit of the fetus, and yet carry risks to both mother and fetus. This paper reviews the ethics of fetal cardiac intervention in fetal left heart disease. It provides the ethical underpinnings for the development and performance of these procedures and outlines a practical ethical framework for counselling families in the face or these cardiac abnormalities. There is a need for careful case selection and a need to review these cases after fetal cardiac intervention. The establishment of registries to collect pre-procedural data and to monitor short and long-term procedural outcomes is expected to strengthen the evidence for ethical decision-making.
Background
SMAD2 is a coregulator that binds a variety of transcription factors in human development. Heterozygous SMAD2 loss‐of‐function and missense variants are identified in patients with congenital heart disease (CHD) or arterial aneurysms. Mechanisms that cause distinct cardiovascular phenotypes remain unknown. We aimed to define transcriptional and epigenetic effects of SMAD2 variants and their role in CHD. We also assessed the function of SMAD2 missense variants of uncertain significance.
Methods and Results
Rare SMAD2 variants (minor allele frequency ≤10 ⁻⁵ ) were identified in exome sequencing of 11 336 participants with CHD. We constructed isogenic induced pluripotent stem cells with heterozygous or homozygous loss‐of‐function and missense SMAD2 variants identified in CHD probands. Wild‐type and mutant induced pluripotent stem cells were analyzed using bulk RNA sequencing, chromatin accessibility (Assay for Transposase‐Accessible Chromatin With Sequencing), and integrated with published SMAD2/3 chromatin immunoprecipitation data. Cardiomyocyte differentiation and contractility were evaluated. Thirty participants with CHD had heterozygous loss‐of‐function or missense SMAD2 variants. SMAD2 haploinsufficiency altered chromatin accessibility at promoters and dysregulated expression of 385 SMAD regulated genes, including 10 CHD‐associated genes. Motifs enriched in differential Assay for Transposase‐Accessible Chromatin peaks predicted that SMAD2 haploinsufficiency disrupts interactions with transcription factors NANOG (homeobox protein NANOG), ETS, TEAD3/4 (transcriptional enhanced associate domain 3/4), CREB1 (cAMP response element binding protein 1), and AP1 (activator protein 1). Compared with SMAD2 ‐haploinsufficient cells, induced pluripotent stem cells with R114C or W274C variants exhibited distinct and shared chromatin accessibility and transcription factor binding changes.
Conclusions
SMAD2 haploinsufficiency disrupts transcription factor binding and chromatin interactions critical for cardiovascular development. Differences between the molecular consequences of loss‐of‐function and missense variants likely contribute to phenotypic heterogeneity. These findings indicate opportunities for molecular analyses to improve reclassification of SMAD2 variants of uncertain clinical significance.
Variants with large effect contribute to congenital heart disease (CHD). To date, recessive genotypes (RGs) have commonly been implicated through anecdotal ascertainment of consanguineous families and candidate gene-based analysis; the recessive contribution to the broad range of CHD phenotypes has been limited. We analyzed whole exome sequences of 5,424 CHD probands. Rare damaging RGs were estimated to contribute to at least 2.2% of CHD, with greater enrichment among laterality phenotypes (5.4%) versus other subsets (1.4%). Among 108 curated human recessive CHD genes, there were 66 RGs, with 54 in 11 genes with >1 RG, 12 genes with 1 RG, and 85 genes with zero. RGs were more prevalent among offspring of consanguineous union (4.7%, 32/675) than among nonconsanguineous probands (0.7%, 34/4749). Founder variants in GDF1 and PLD1 accounted for 74% of the contribution of RGs among 410 Ashkenazi Jewish probands. We identified genome-wide significant enrichment of RGs in C1orf127 , encoding a likely secreted protein expressed in embryonic mouse notochord and associated with laterality defects. Single-cell transcriptomes from gastrulation-stage mouse embryos revealed enrichment of RGs in genes highly expressed in the cardiomyocyte lineage, including contractility-related genes MYH6, UNC45B , MYO18B , and MYBPC3 in probands with left-sided CHD, consistent with abnormal contractile function contributing to these malformations. Genes with significant RG burden account for 1.3% of probands, more than half the inferred total. These results reveal the recessive contribution to CHD, and indicate that many genes remain to be discovered, with each likely accounting for a very small fraction of the total.
Background and Objectives:Medication safety is critical for pediatric cardiac care, especially in low- and middle-income countries (LMICs), where limited resources contribute to high rates of medication errors. Studies in LMICs have shown that pharmacist interventions can reduce medication errors by up to 57% and proved that clinical pharmacists are essential for ensuring accurate and optimized medication use. This study aims to evaluate the role of clinical pharmacist interventions to rectify prescription errors in a pediatric cardiac care setting in Pakistan.
Methods:This single-center retrospective study was conducted from January to August 2022 in a pediatric cardiac ward at the National Institute of Cardiovascular Diseases. Pediatric patients of all age groups and genders diagnosed with acquired, inherited, or congenital heart diseases were included. We reviewed patient files for any prescription changes made by the clinical pharmacist, based on a comprehensive review of the patient profile, treatment regimens, and laboratory results, to ensure safe and effective pharmacotherapy.
Results:260 pharmacist interventions were observed among 2754 patients over eight months, demonstrating a significant role in mitigating medication errors. The interventions addressed wrong doses (126), incorrect frequencies (101), redundant coverage (23), and therapy duration errors (8). Antibiotics were the most frequent source of prescription errors, accounting for 81% of the interventions.
Conclusion:Clinical pharmacists’ involvement in pediatric cardiac care significantly reduces medication errors in LMICs, as demonstrated by this study. These findings underscore the need to integrate clinical pharmacists into multidisciplinary teams to enhance medication safety and improve patient outcomes.
Objective. To summarize the characteristics and reliability of clinical practice guidelines (CPG) for diagnosing and managing common congenital heart diseases (CHD). Methods. We conducted a scoping review of CPG for CHD (ventricular septal defects, atrial septal defects, patent ductus arteriosus, and coarctation of aorta) published or updated from 2018 to April 2023. We searched in general search engines, CPG repositories, and webpages of organizations that elaborate CPG. To assess the reliability of CPG, we used the Appraisal of Guidelines Research and Evaluation II (AGREE-II) tool, with a score ≥70% considered acceptable quality. Results. Twenty-one CPG were identified. Only 6 (28.6%) conducted systematic reviews, and none achieved an acceptable AGREE-II score. “Scope and purpose” had the highest scores, while “stakeholder involvement” had the lowest. Conclusions. Most CPG for CHD lack systematic reviews and do not meet acceptable quality standards, underscoring the need for evidence-based guidelines to guide diagnosis and management effectively.
Congenital heart disease (CHD) is the most common congenital anomaly, leading to an increased risk of neurodevelopmental abnormalities in many children with CHD. Understanding the neurological mechanisms behind these neurodevelopmental disorders is crucial for implementing early interventions and treatments. In this study, we recruited 83 infants aged 12–26.5 months with complex CHD, along with 86 healthy controls (HCs). We collected multimodal data to explore the abnormal patterns of cerebral cortex development and explored the complex interactions among blood oxygen‐carrying capacity, cortical development, and gross motor skills. We found that, compared to healthy infants, those with complex CHD exhibit significant reductions in cortical surface area development, particularly in the default mode network. Most of these developmentally abnormal brain regions are significantly correlated with the blood oxygen‐carrying capacity and gross motor skills of infants with CHD. Additionally, we further discovered that the blood oxygen‐carrying capacity of infants with CHD can indirectly predict their gross motor skills through cortical structures, with the left middle temporal area and left inferior temporal area showing the greatest mediation effects. This study identified biomarkers for neurodevelopmental disorders and highlighted blood oxygen‐carrying capacity as an indicator of motor development risk, offering new insights for the clinical management CHD.
Abstract
Objectives: To evaluate the placental vascular architecture using MV Flow™ imaging for analyzing vascular distribution per region of biological tissue in isolated congenital heart diseases (CHD), CHD associated with extracardiac malformations (EXM) and normal pregnancies, and to explore the relationship of fetal Doppler flow parameters and growth to placental perfusion in these conditions.
Methods: Placental microvascular structure was assessed using MV-Flow™ in a total of 227 normal fetuses and 139 with CHD; fetuses with gestational age ranging from 11 to 41 weeks were included. Placental vascular indices (VIMV %) was acquired at three different segments of each placenta (upper, middle, and lower regions). Doppler pulsatility indices of fetal umbilical artery (UA), middle cerebral artery (MCA), ductus venosus (DV), uterine artery (UtA), and cerebroplacental ratio were measured in both normal and CHD groups. The CHD group was divided into two subgroup based on whether it is associated with EXM.
Results: Compared to the control group, the CHD with EXM group exhibited a significantly lower VIMV % for the upper, middle, and lower regions of the placenta (P = .005; P = .018; P = .039, respectively). In the total CHD group, VIMV % decreased in the middle segment of placenta in the 2nd trimester compared to the control group. But the VIMV % of upper and middle segments decreased in the 3rd trimester. Both subgroups, EXM and isolated CHD, showed similar distribution of gestational weeks. Doppler vascular indices were significantly different compared to normal in the total CHD group for UA-pulse index (PI), DV-PI, right UtA-PI, and left UtA-PI, with similar differences from normal for the CHD with EXM group. DV-PI was the only significantly different Doppler vascular parameter for the isolated CHD group compared to normal.
Conclusions: For the first time, MV-Flow™ imaging demonstrated reduced placental vascularity in fetuses with CHD and ECM and in fetuses with isolated CHD in the 3rd trimester of pregnancy. Application of MV-Flow™ as part of serial fetal echocardiographic surveillance in cases of CHD may allow for better understanding of the development of placental abnormalities.
Keywords: MV‐Flow™; congenital heart disease; fetal; placental microvascular.
Congenital structural heart disease (CHD) is the leading cause of infant death from birth defects. Postnatal survival primarily depends on the type and severity of the defect. In addition, worse cardiac prognosis is observed when extra-cardiac anomalies (ECA) are associated. This retrospective chart review was aimed at finding markers for short-term outcome prediction of prenatally-diagnosed complex CHD, focusing in particular on the impact of CHD category, of CHD severity score and of prenatal or postnatal diagnosis of ECA or chromosomal anomalies on 4 primary outcomes: termination of pregnancy (TOP), intrauterine fetal demise, neonatal mortality and 1-year-survival rate. We reviewed medical files from 381 fetuses, presenting at our center between 2018 and 2021 with CHD for which prenatal advice by a pediatric cardiologist was sought. 341 fetuses met the inclusion criteria for the study. Twin pregnancies (7.62%; OR 4.76 (p < 0.001)) and pregnancies resulting from assisted reproductive technology (7.33%; OR 2.44 (p < 0.001)) were more prevalent compared to the general population. CHD categories and CHD severity scores, ranging from A (extremely high risk based on CHD or ECA type) to D (low risk), were assigned to each fetus. Prenatal or postnatal chromosomal microarray results were available for 232 fetuses (68%) and were abnormal in 30 (12.9%). Logistic regression analysis was used to determine significant predictors for the primary outcomes ‘TOP’, ‘postnatal demise before the age of 1 month’ and ‘survival at the age of 1 year’. TOP was carried out significantly more with: prenatal genetic diagnosis, severity score A and severity score B. Interestingly, a prenatal genetic diagnosis was negatively correlated with pregnancy continuation, but it was not a significant predictor for postnatal mortality, while a postnatal diagnosis of a genetic disorder impacted early but not late postnatal mortality. In addition, postnatal mortality both before the age of 1 month or before the age of 1 year was significantly associated with lower postmenstrual age at birth, CHD severity score B and major ECA at birth. These results underscore the importance of genotyping and of accurate cardiac and extracardiac phenotyping for prognostication in fetuses with CHD.
Congenital heart disease (CHD) represents a major birth defect associated with substantial morbidity and mortality. Although environmental factors are acknowledged as potential contributors to CHD, the underlying mechanisms remain poorly understood. Bisphenol A (BPA), a common endocrine disruptor, has attracted significant attention due to its widespread use and associated health risks. This study examined the effects of maternal BPA exposure on fetal heart development in a murine model. The findings indicated that high‐dose BPA exposure resulted in fetal growth restriction, myocardial wall thinning, and ventricular septal defects. Transcriptomic analysis revealed downregulation of genes associated with mitochondrial energy synthesis and cardiomyocyte development following high‐dose BPA exposure. Functional assays demonstrated that high‐dose BPA exposure impaired mitochondrial respiration reduced ATP production, disrupted mitochondrial membrane potential, and increased intracellular reactive oxygen species levels in fetal cardiomyocytes. These results elucidate the detrimental effects of BPA on fetal heart development and mitochondrial function, providing insights into potential mechanisms linking environmental chemical exposure to CHD.
Background
Neurodevelopmental disability is a common long-term concern following surgery for congenital heart disease (CHD). Little information is available from low-resource environments where the majority of children with CHD are born. Several challenges in the CHD care continuum exist in such environments.
Methods
We followed 1346 infants who were operated for CHD using cardiopulmonary bypass from five paediatric cardiac programmes across India. The neurodevelopmental assessment was done using the Developmental Assessment Scale for Indian Infants (DASII) at 6 months after surgery.
Results
A total of 1145 (94.8%) infants were alive at 6 months and 127 (11.1%) were lost to follow-up. The mean age of participants at baseline was 5.2 (3.6) months. The mean motor developmental quotient (DMoQ) and mental developmental quotient (DMeQ) of the remaining 1018 infants were 81.8 (69.5, 93.0) and 87.7 (77.1, 95.7), respectively. A total of 262 (25.7%) infants had motor developmental delay and 157 (15.4%) had mental developmental delay. Syndromic association, younger age at surgery, duration of mechanical ventilation and head circumference were significantly associated with DMoQ. The DMeQ was associated with syndromes, duration of hospital and intensive care unit stay and socioeconomic status. The preoperative condition did not impact mental and motor development. Motor clusters with maximum delay included body control and locomotion. Mental clusters with maximum delay included reaching and manipulation, social interaction-imitative behaviour and vocabulary comprehension.
Conclusions
Survivors of infant heart surgery experience significant motor and mental neurodevelopmental delay. This delay is associated with similar factors reported by earlier studies. As more high-risk infants undergo cardiac surgery in low-resource settings, a growing population will require significant societal resources for neurodevelopmental assessment as well as neurodevelopmental rehabilitation. These resources include trained personnel for comprehensive developmental assessment of survivors of CHD surgery, as well as infrastructural requirements for dedicated assessment rooms in centres providing surgical care for CHD patients.
Background
Reduced exercise capacity is associated with a poor prognosis in adult patients with congenital heart disease (CHD). Reducing sedentary behavior (SB) and increasing physical activity (PA) could be potential strategies that may contribute to enhanced fitness and prevention of acquired cardiovascular disease in adult patients with CHD. The present study aimed to examine the association of SB and PA with exercise capacity in adult patients with CHD.
Methods
Ninety-six adult patients with CHD (age: 18–74 years) underwent measurements of peak oxygen uptake (VO2), % predicted peak VO2, and time spent in SB, light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA). Three regression models (single-activity, partition, and isotemporal substitution) were used to examine the associations of the time spent in SB, LPA, and MVPA with peak VO2 and % predicted peak VO2.
Results
In the single-activity and partition models, time spent in MVPA was consistently associated with peak VO2 and % predicted peak VO2. The isotemporal substitution model indicated that replacing 10-min of SB with the same duration of MVPA was associated with a higher peak VO2 (by 0.454 mL/min/kg [0.100 mL/min/kg, 0.807 mL/min/kg]) and % predicted peak VO2 (by 1.810 % [0.594 %, 3.026 %]).
Conclusion
These findings suggest that reducing SB time and increasing PA time are associated with improved exercise capacity in adult patients with CHD.
Background
Tetralogy of Fallot is one of the critical congenital heart defects needing intervention within the first year of life.
Objective
This review aims to systematically assess the prevalence of Tetralogy of Fallot among children and adolescents with congenital heart defects in Sub-Saharan Africa from January 2000 to January 2024.
Methods
All original observational studies focused on children and adolescent population diagnosed with congenital heart defects within Sub-Saharan Africa; reported the primary outcome of interest were included. Prisma guidelines were utilized to perform this systematic review and meta-analysis. Electronic databases including Medline (PubMed), Scopus, Google Scholar, and African Index Medicus were searched. A weighted inverse variance random-effects model was employed to estimate the pooled prevalence of Tetralogy of Fallot.
Results
Thirty-one studies included encompassing a total of 11,265 participants from 15 Sub-Saharan African countries with representation from Southern (4 studies, 619 participants), Central (5 studies, 2,220 participants), Eastern (11 studies, 3,384 participants), and Western (11 studies, 5,042 participants). Cross-sectional studies comprised (25 studies, 8,909 participants), and cohort design (6 studies, 2,356 participants). The analysis revealed a pooled prevalence of 10% (95% CI: 9%; 12%) with I² (77%, p-value < 0.01). The subgroup analysis based on geographic regions revealed statistically significant difference.
Conclusions and future implications
The prevalence of Tetralogy of Fallot observed was found considerably higher compared to global estimate and reports of developed countries. In a subgroup analysis based on the geographic region, a surprisingly high prevalence was reported across all regions of Sub-Saharan Africa. The substantial disparities and high prevalence observed underscores the complex interplay of factors influencing occurrence of Tetralogy of Fallot. Identifying the true scope of Tetralogy of Fallot burden may help policymakers and healthcare providers to prioritize interventions, optimize resource allocation, and potentially improve its outcomes in Sub-Saharan Africa.
Disorders of the pulmonic valve (PV) receive considerably less attention than other forms of valvular heart disease. Due to the dramatically improved survival of children with congenital heart disease over the last 5 decades, there has been a steady increase in the prevalence of adults with congenital heart disease, which necessitates that clinicians become familiar with the anatomy and the evaluation of right ventricular outflow tract and PV anomalies. A multimodality imaging approach using echocardiography, cardiac computed tomography, and magnetic resonance imaging is essential for a comprehensive evaluation of the anatomy and function of the right ventricular outflow tract, PV, and supravalvular region. As clinical presentation is often insidious with nonspecific symptoms, yet morbidity and mortality associated with severe untreated PV disease are significant, a high index of suspicion coupled with appropriate use of imaging techniques is critical in facilitating timely diagnosis and treatment. In this review, we aim to present a comprehensive approach to the diagnosis of PV disease and associated right ventricular outflow tract or supravalvular pulmonary stenosis, including optimal use of multimodality imaging to facilitate timely diagnosis, optimize therapeutic strategies, enhance postprocedural surveillance, and ultimately improve patient outcomes.
Early diagnosis and percutaneous closure of symptomatic adult atrial septal defects can enhance cardiac function and relieve symptoms. Thorough pre‐procedural evaluation and diligent follow‐up care are essential for achieving the best outcomes and ensuring long‐term success.
The pulmonary valve (PV), although often less emphasized than other heart valves, is crucial for cardiac function and hemodynamics. Historically, the PV has been underrepresented in echocardiographic assessments due to its rare involvement in pathological conditions, particularly in adults. Additionally, the anatomical position of the PV makes it one of the most challenging valves to visualize using conventional echocardiography. Traditional two‐dimensional (2D) techniques, while foundational, have limitations in capturing the full spectrum of valve pathology and dynamics. Recent advancements in echocardiography, especially the integration of three‐dimensional (3D) imaging, have significantly enhanced the assessment of PV disorders. 3D echocardiography (3DE) offers superior accuracy in visualizing valve morphology and function, overcoming the limitations of angle dependency and suboptimal imaging planes typical of 2D assessments. This evolution in imaging techniques facilitates more precise diagnoses and improved management of conditions such as pulmonary stenosis (PS) and regurgitation (PR). This review explores the transition from conventional echocardiographic methods to advanced approaches that are reshaping our understanding of the PV, emphasizing the importance of incorporating these cutting‐edge techniques into routine clinical practice to enhance patient outcomes.
Congenital heart defects (CHDs) are caused by a complex interaction between numerous genetic and environmental risk factors, some of which may differ between different populations. A case–control study was conducted among 1232 newborns, including 308 patients with isolated CHDs (cases) and 924 infants without birth defects (controls), born all during the period 2009–2023 at the Hospital Civil de Guadalajara “Dr. Juan I. Menchaca” (Guadalajara, Mexico). Potential parental risk factors for CHDs were compared using multivariate logistic regression analysis to evaluate the deviance explained by different variables of interest. Consanguinity [adjusted odds ratio (aOR) = 3.3; 95% confidence interval (CI) 1.3–8.5], relatives with CHD (aOR = 8.5; 95% CI 5.3–13.8), maternal first‐trimester exposure to diabetes (aOR = 3.5; 95% CI 2.4–5.1), hypertension (aOR = 2.6; 95% CI 1.5–4.4), alcohol consumption (aOR = 1.5; 95% CI 1.0–2.1), and illicit drug use (aOR = 2.4; 95% CI 1.2–5.3), as well as for the paternal history of alcohol consumption (aOR = 1.4; 95% CI 1.0–1.8) and illicit drug use (aOR = 2.7; 95% CI 1.7–4.1), were associated with CHDs. Contrarily, aOR for maternal age ≤19 years (aOR = 0.6; 95% CI 0.4–0.8) and maternal first‐trimester coffee consumption (aOR = 0.7; 95% CI 0.5–0.9) have protective odds. Our results suggest that genetic factors, maternal diseases, environmental exposures, and reproductive factors can increase the occurrence of isolated CHDs in our sample, and they are discussed as clues in its pathogenesis.
Congenital heart disease (CHD) is a complex common defect in pediatric patients, and definitive treatment is usually cardiac surgery, especially for diseases with complex aetiology (ie, Critical CHD). While significant success has been reported due to improvement in diagnosis and treatment, the risk of mortality is still relatively higher than in the general population. Advances in surgical and post-surgical clinical management continue to increase survival in pediatric patients. However, mechanical ventilation (MV) during and after post-surgical procedures is linked with potential complications that may drive morbidity and mortality. Standard clinical practice dictates weaning patients off MV within the first 24 hours after surgery. However, various factors may increase the risk of extubation failure (EF), reintubation, and prolonged MV (PMV). Generally, PMV has been linked with increased length of pediatric intensive care unit (PICU) stay, morbidity, and higher risk of post-cardiac surgery mortality. The risk of PMV may be either preexisting (preoperative), perioperative/intraoperative, and/or postoperative, with the tendency to define the clinical course and patient outcomes. Monitoring and understanding the physiological dynamics of these risk factors may provide an opportunity for better and improved clinical management, which may translate into better patient outcomes. This review delves into the risk factors of extubation failure, reintubation, and PMV in pediatric cardiac surgery patients with complex (CHD) and the potential preventative measures to improve patients’ outcomes.
Background
Recently, fentanyl has become prevalent as a sedative premedication.
Methods
A non-inferiority parallel design quadruple-blinded randomised controlled trial of 1- to 7-year-old children scheduled for elective cardiac surgery was conducted. Participants were assigned a 1:1 allocation ratio to a control group ( n = 50) given a parenteral formulation of midazolam 0.5 mg/kg and an intervention group ( n = 50) given a parenteral formulation of fentanyl 10 μg/kg 30 min before admission to the operating room.
Results
Fentanyl was shown to be inferior when compared to midazolam during inhalational induction but not in the ‘after premedication’ and ‘during separation’ periods. A lower percentage of children disliked the medication in the fentanyl group.
Conclusions
A parenteral formulation of fentanyl can be a satisfactory alternative when given orally as a sedative pre-anaesthetic medication in paediatric cardiac surgery before admission to the operating room.
Neddylation is a highly conserved post‐translational modification that plays critical roles in various cellular processes through the modulation of cullins and non‐cullin substrates. While neddylation is known to be essential for embryonic development, tumor growth, and organogenesis of different tissues, its role in cardiogenesis remains unexplored. Here, we investigated the role of neddylation in early cardiac development by deleting the gene encoding a regulatory subunit of the NEDD8‐specific E1 activating enzyme, Nae1, globally and in a heart‐specific fashion via Nkx2‐5Cre. Global deletion of Nae1 in mice led to embryonic lethality before embryonic day (E) 8.5, whereas cardiac‐specific NAE1 knockout mice died at around E12.5 with pronounced cardiac effusion and peripheral hemorrhage, characteristic of cardiac failure. Histological analysis revealed significant thinning of the compact myocardium and reduced trabeculae in mutant hearts, which were accompanied by reduced cardiomyocyte proliferation. Unbiased transcriptomic analysis identified perturbations in cardiomyocyte proliferation and myofibril architecture in mutant hearts. Subsequent analysis showed that loss of NAE1 disrupted sarcomere assembly dysregulated the expression of several important contractile proteins, and impaired mitochondrial function in the developing heart, which was accompanied by downregulation of key cardiac transcription factors including NKX2‐5 and SRF. Collectively, our findings demonstrate the essential role of neddylation in cardiogenesis at least in part by driving cardiomyocyte proliferation and myofibrillogenesis.
Background
Congenital heart disease (CHD) is the most common birth defect, affecting 40,000 births annually in the United States. Despite advances in medical care, CHD is often a chronic condition requiring continuous management and education. Effective care management depends on children’s understanding of their condition. This highlights the need for targeted health educational interventions to enhance health literacy among children with CHD.
Objective
This scoping review aims to map and explore existing health educational interventions for children with CHD. The review identifies the types of interventions, target populations, delivery methods, and assessed outcomes. The goal is to consolidate fragmented research, identify gaps, and establish future research agendas.
Methods
Comprehensive searches were conducted in February 2024 using the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) framework across multiple databases: APA PsycINFO, MedlinePlus via Ovid, Web of Science, ACM Digital Library, Scopus, and EBSCOhost (CINAHL Complete, CINAHL Ultimate, Health Source: Nursing/Academic Edition, and ERIC). The search covered health care, design, and human-computer interaction disciplines to capture the interdisciplinary nature of CHD health educational interventions. There was no predefined time limit due to the limited number of relevant studies. Eligible studies were in English, published in peer-reviewed journals, and focused on primary data about educational health interventions for children with CHD. We extracted and synthesized data using thematic analysis.
Results
The review identified 11 studies: 9 randomized controlled trials and 2 observational studies. These used 6 educational strategies: 3D patient-specific models (n=3), habit formation interventions (n=2), empowerment-based health education programs (n=2), rehabilitation interventions (n=2), web-based portals (n=1), and videotape presentations (n=1). Interventions ranged from brief outpatient sessions to 1.5-year programs, with follow-up from none to 24 months. Studies aimed to improve coping, self-management, and knowledge for children with CHD and their families. The most frequently used assessment method was the independent samples t test (n=4) for pre- and postassessments, and all 11 studies used questionnaires, 8 of which incorporated qualitative feedback. The target participants for these interventions were children aged 13 years and older (n=3), parents (n=2), and children of various ages and their parents (n=6). Outcomes included improved children’s health literacy, reduced parental burden, and increased health care provider efficiency.
Conclusions
This review underscores the critical need for tailored educational interventions for children with CHD. Current research mainly focuses on adolescents and relies heavily on parental involvement, possibly overlooking the specific needs of younger children younger than 13 years of age. It is essential to develop engaging, age-appropriate interventions that actively involve children with CHD in their health care journey. Effective health educational interventions are crucial in empowering these young patients and improving their long-term health outcomes.
Background: Cognitive impairment is the most common long‐term complication in children with congenital heart disease (CHD) and is closely related to the brain network. However, little is known about the impact of CHD on brain network organization. This study aims to investigate brain structural network properties that may underpin cognitive deficits observed in children with Tetralogy of Fallot (TOF).
Methods: In this prospective study, 29 preschool‐aged children diagnosed with TOF and 19 without CHD (non‐CHD) were enrolled. Participants underwent diffusion tensor imaging (DTI) scans alongside cognitive assessment using the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence—fourth edition (WPPSI‐IV). We constructed a brain structural network based on DTI and applied graph analysis methodology to investigate alterations in diverse network topological properties in TOF compared with non‐CHD. Additionally, we explored the correlation between brain network topology and cognitive performance in TOF.
Results: Although both TOF and non‐CHD exhibited small‐world characteristics in their brain networks, children with TOF significantly demonstrated increased characteristic path length and decreased clustering coefficient, global efficiency, and local efficiency compared with non‐CHD (p < 0.05). Regionally, reduced nodal betweenness and degree were found in the left cingulate gyrus, and nodal efficiency was decreased in the right precentral gyrus and cingulate gyrus, left inferior frontal gyrus (triangular part), and insula (p < 0.05). Furthermore, a positive correlation was identified between local efficiency and cognitive performance (p < 0.05).
Conclusion: This study elucidates a disrupted brain structural network characterized by impaired integration and segregation in preschool TOF, correlating with cognitive performance. These findings indicated that the brain structural network may be a promising imaging biomarker and potential target for neurobehavioral interventions aimed at improving brain development and preventing lasting impairments across the lifetime.
Right ventricular outflow dysfunction, manifesting as stenosis, regurgitation, or both, is nearly universal in patients with repaired tetralogy of Fallot, precipitating a complex pathophysiological cascade that leads to increasing rates of morbidity and mortality with advancing age. As the number of adolescent and adult patients with repaired tetralogy of Fallot continues to grow as a result of excellent survival during infancy, the need to improve late outcomes has become an urgent priority. This American Heart Association scientific statement provides an update on the current state of knowledge of the pathophysiology, methods of surveillance, risk stratification, and latest available therapies, including transcatheter and surgical pulmonary valve replacement strategies, as well as management of life-threatening arrhythmias. It reviews emerging evidence on the roles of comorbidities and patient-reported outcomes and their impact on quality of life. In addition, this scientific statement explores contemporary evidence for clinical choices such as transcatheter or surgical pulmonary valve replacement, discusses criteria and options for intervention for failing implanted bioprosthetic pulmonary valves, and considers a new approach to determining optimal timing and indications for pulmonary valve replacement.
Background
The structural abnormality of the heart and its blood vessels at the time of birth is known as congenital heart disease. Every year in Pakistan, sixty thousand children are born with CHD, and 44 in 1000 die before they are a month old. Various studies used different techniques to estimate the risk factors of congenital heart disease, but these techniques suffer from a deficiency of capacity to present human understanding and a deficiency of adequate data. The current study provided an innovative approach by defining the latent variables to handle this issue and building a reasonable model.
Method
Data used in this study has been collected from mothers and hospital records of the children. The dataset contains information on 3900 children who visited the OPD of the Chaudry Pervaiz Elahi Institute of Cardiology (CPEIC) Multan, Pakistan from October 2021 to September 2022. The latent variables were defined from the data and structural equation modeling was used to model them.
Result
The results show that there are 53.6% of males have acyanotic CHD and 54.5% have cyanotic CHD. There are 46.4% of females have acyanotic CHD and 45.5% have cyanotic CHD. The children who have no diabetes in the family are 64.0% and children who have diabetes in the family are 36.0% in acyanotic CHD, the children who have no diabetes in the family are 59.7% and children have diabetes in the family are 40.3% in cyanotic CHD. The value of standardized root mean residual is 0.087 is less than 0.089 which shows that the model is a good fit. The value of root mean square error of approximation is 0.113 is less than 0.20 which also shows the good fit of the model.
Conclusion
It was concluded that the model is a good fit. Also, the latent variables, socioeconomic factors, and environmental factors of mothers during pregnancy have a significant effect in causing cyanotic while poor general health factor increases the risk of Acyanotic congenital heart disease.
Objectives. Case management, which is defined as a fully collaborative process that includes evaluation, planning, execution, coordination and supervision, has been widely used in the field of chronic diseases. However, the clinical effect of case management in pediatric patients with congenital heart disease (CHD) is unclear. This study was to explore the effects of case management model in pediatric patients with CHD. Methods. A total of 110 pediatric CHD patients referred to our center from January 2018 to January 2020 were enrolled for analysis. Patients were randomly assigned to a case management (experimental) group or a conventional nursing (control) group. Patient satisfaction, quality of life, and clinical outcomes were compared between the 2 groups. Results. Compared with that in the control group, patient satisfaction rate was significantly greater in the experimental group. Furthermore, the experimental group showed more significant improvement in quality of life than the control group did (73.8 ± 12.3 vs 66.5 ± 14.2, P < .001). In addition, the readmission rate in the experimental group was significantly lower than that in the control group (5% vs 20%, P = .022). Conclusions. Case management mode can be effectively applied in pediatric patients with CHD, which can improve patient satisfaction rate, health-related quality of life and lower the readmission rate.
Fetal cardiac intervention consists of a novel and evolving technique for the intrauterine treatment of a subset of patients with congenital heart diseases, which aims to improve hemodynamics, reduce secondary damage, and achieve better postnatal outcomes. Nevertheless, the risks and benefits of this therapy remains subject to controversy. This review describes the rationale, selection criteria, and technical features for the most frequently performed fetal cardiac interventions. In addition, we provide a comprehensive overview of the medical literature, exploring the clinical implications of each therapy.
Objective:
The transannular patch remains the most common procedure performed for patients with Tetralogy of Fallot (TOF) with pulmonary stenosis. Pulmonary regurgitation has a negative impact on early and late outcomes. To address this issue pulmonary valve-sparing repair (PVSR) has been developed. Our study goal is to evaluate the mid-term outcomes (five years) of PVSR at our institution.
Material and methods:
The data were collected retrospectively from June 2014 to June 2022. A total of 390 patients had total repair of TOF. Among these, PVSR was performed in 154 (39.4%) patients. The mid-term outcomes on the status of the pulmonary valve gradient, degree of pulmonary regurgitation, reintervention rate, and mid-term survival after PVSR were investigated.
Results:
The median age at time of TOF repair was 12 (interquartile range [IQR]: 8-48) months and the median weight was 7.9 (IQR: 3.1-49.5) kg. The mean preoperative right ventricular outflow tract (RVOT) gradient was 77 ± 19.6 mm Hg. All patients had a pulmonary valve Z score of more than -2.5. The post-repair mean RV/LV pressure ratio was 0.49 ± 0.12. There was no surgical mortality. The median follow-up was 3 years (6 months to 8 years). The reintervention rate on the pulmonary valve was 4/154 (2.6%) at five years. The freedom from reintervention and from developing moderate pulmonary valve regurgitation at 5 years was 95% (151/154) and 77% (119/154), respectively.
Conclusion:
Pulmonary valve-sparing repair gives good mid-term outcomes in a specific group of patients with TOF. Reintervention rates are very low and the peak gradient across the pulmonary valve came down in the majority of patients during mid-term follow up. An RVOT gradient more than 40mm Hg at discharge predicts a high risk of need for reintervention. We continue to monitor our patients for the long term outcome.
Background
The three-dimensional balanced-steady-state-free-precession (3D bSSFP) whole-heart (WH) technique has long been used to depict cardiac morphology in congenital heart disease (CHD) but is prone to banding artifacts. The Relaxation Enhanced Angiography without Contrast and Triggering (REACT) sequence is an alternative method that is resistant to off-resonance effects.
Objective
To evaluate cardiac structures and great vessels in CHD patients using 3D WH REACT sequence and compare it to 3D WH bSSFP sequence.
Materials and methods
This study was approved by the Institutional Review Board. Thirty CHD patients were prospectively enrolled. Contrast-to-noise ratio (CNR), image quality, and cross-sectional area (CSA) were analyzed. Categorical data were compared with a Wilcoxon signed-rank test and normally distributed variables with a t-test.
Results
Thirty patients (16 females) participated in this study (median age 17, range 5 months to 52 years). REACT showed higher CNR in all pulmonary veins (all P<0.05), while 3D bSSFP had higher CNR in the right ventricle (P<0.001) and right pulmonary artery, (P=0.04). Image quality favored 3D bSSFP in the right atrium and ventricle (both P<0.001), main pulmonary artery (P=0.02), and coronary arteries (left: P<0.001, right: P=0.01). REACT outperformed 3D bSSFP for the pulmonary veins (all P<0.05) from image quality perspective. CSA measurements were not significantly different between REACT and 3D bSSFP (all P≥0.05).
Conclusion
The REACT method is associated with improved image quality and CNR for pulmonary veins, with CSA measurements concordant with 3D bSSFP in CHD patients, while bSSFP shows better performance for imaging cardiac chambers and coronary arteries.
Graphical Abstract
Background
Early detection of left and right ventricular systolic dysfunction (LVSD and RVSD respectively) in children can lead to intervention to reduce morbidity and death. Existing artificial intelligence algorithms can identify LVSD and RVSD in adults using a 12‐lead ECG; however, its efficacy in children is uncertain. We aimed to develop novel artificial intelligence–enabled ECG algorithms for LVSD and RVSD detection in pediatric patients.
Methods and Results
We identified 10 142 unique pediatric patients (age≤18) with a 10‐second, 12‐lead surface ECG within 14 days of a transthoracic echocardiogram, performed between 2002 and 2022. LVSD was defined quantitatively by left ventricular ejection fraction (LVEF). RVSD was defined semiquantitatively. Novel pediatric models for LVEF ≤35% and LVEF <50% achieved excellent test areas under the curve of 0.93 (95% CI, 0.89–0.98) and 0.88 (95% CI, 0.83–0.94) respectively. The model to detect LVEF <50% had a sensitivity of 0.85, specificity of 0.80, positive predictive value of 0.095, and negative predictive value of 0.995. In comparison, the previously validated adult data‐derived model for LVEF <35% achieved an area under the curve of 0.87 (95% CI, 0.84–0.90) for LVEF ≤35% in children. A novel pediatric model for any RVSD detection reached a test area under the curve of 0.90 (0.87–0.94).
Conclusions
An artificial intelligence–enabled ECG demonstrates accurate detection of both LVSD and RVSD in pediatric patients. While adult‐trained models offer good performance, improvements are seen when training pediatric‐specific models.
Background
Uninterrupted folate metabolism plays a vital role in embryonic development, ensuring a supply of one‐carbon‐activated folate cofactors for essential processes. Folate deficiency has been implicated in the development of orofacial clefts (OFC) and congenital heart disease (CHD). Although both malformations have been extensively studied in lieu of folate deficiency, the results of corresponding studies are ambiguous due to the interplay of maternal and fetal genomes controlling folate metabolism in the developing fetus.
Methods
We used the innovative study design to compare affected and unaffected siblings from the same mother, thus minimizing the effect of the maternal genome. Thus, it might be possible to identify genetic markers of congenital malformations that pertain exclusively to the child. This study compared demographic and environmental factors between OFC or CHD‐affected and unaffected pregnancies as well as the presence of polymorphisms in genes of folate metabolism between OFC or CHD‐affected and unaffected siblings.
Results
Only the maternal fever in the first trimester was a risk factor for OFC, whereas the maternal advanced age, medication administration, and common polymorphism in the FPGS gene increased the risk of CHD formation. Both OFC and CHD formation were associated with a higher number of variant loci in genes of folate–methionine cycles.
Conclusions
Both OFC and CHD formation were associated with a higher number of mutated loci in genes of folate–methionine cycles, indicating polygenic and possibly multifactorial inheritance.
BACKGROUND
Congenital heart disease is most commonly seen in neonates and it is a major cause of pediatric illness and childhood morbidity and mortality.
AIM
To identify and build the best predictive model for predicting cyanotic and acyanotic congenital heart disease in children during pregnancy and identify their potential risk factors.
METHODS
The data were collected from the Pediatric Cardiology Department at Chaudhry Pervaiz Elahi Institute of Cardiology Multan, Pakistan from December 2017 to October 2019. A sample of 3900 mothers whose children were diagnosed with cyanotic or acyanotic congenital heart disease was taken. Multivariate outlier detection methods were used to identify the potential outliers. Different machine learning models were compared, and the best-fitted model was selected using the area under the curve, sensitivity, and specificity of the models.
RESULTS
Out of 3900 patients included, about 69.5% had acyanotic and 30.5% had cyanotic congenital heart disease. Males had more cases of acyanotic (53.6%) and cyanotic (54.5%) congenital heart disease as compared to females. The odds of having cyanotic was 1.28 times higher for children whose mothers used more fast food frequently during pregnancy. The artificial neural network model was selected as the best predictive model with an area under the curve of 0.9012, sensitivity of 65.76%, and specificity of 97.23%.
CONCLUSION
Children having a positive family history are at very high risk of having cyanotic and acyanotic congenital heart disease. Males are more at risk and their mothers need more care, good food, and physical activity during pregnancy. The best-fitted model for predicting cyanotic and acyanotic congenital heart disease is the artificial neural network. The results obtained and the best model identified will be useful for medical practitioners and public health scientists for an informed decision-making process about the earlier diagnosis and improve the health condition of children in Pakistan.
Atrial switch procedures such as the Mustard operation were previously popular for the complete transposition of the great arteries (i.e. dextro-transposition of the great arteries [d-TGA]). Patients with d-TGA who underwent atrial switch procedures approximately three decades ago have now entered adulthood. A female patient in her 30s with d-TGA had a paradoxical embolic stroke following the initiation of a low-dose oestrogen plus progesterone oral pill for dysmenorrhoea. She underwent Mustard surgery when she was 2 years old. Following a series of procedures including implantation of a permanent pacemaker that was required because of sinus node dysfunction, she had reached adulthood, was living by herself and working independently. One month after taking the low-dose oestrogen plus progesterone oral pill, venous thrombosis occurred in the left soleus and left peroneal veins; and she experienced an acute ischaemic stroke in the right middle cerebral artery area. Transoesophageal echocardiography revealed that the shunt was present only during the Valsalva manoeuvre. Based on the examinations, the patient was diagnosed with juvenile ischaemic stroke as a result of a paradoxical embolism. These findings suggest that paradoxical cerebral embolism can occur as a late complication in patients with d-TGA who underwent the Mustard operation as children.
Atrial septal defects (ASDs) are among the most prevalent congenital cardiac malformations. Closure of the defect and repair of associated cardiac malformations are typically indicated if an ASD is hemodynamically significant or symptomatic. This narrative review aims to summarize key aspects of surgical ASD closures. A non-systematic literature review was conducted to cover surgically relevant aspects of (developmental) anatomy, morphology, and treatment. ASDs result from diverse developmental alterations, leading to subtype-specific associated cardiac malformations, meaning surgical therapy varies accordingly. Presently, surgical repair yields excellent outcomes for all ASD subtypes, with minimally invasive approaches, especially in adults, increasingly employed for ASD closure. Surgical ASD repair is safe with excellent results. However, familiarity with ASD subtypes and typically associated lesions is crucial for optimal patient management.
Genetic factors play a significant role in the development of congenital heart disease (CHD). Many studies on the genetics of CHD have been published worldwide; however, no research has assessed and mapped the global research landscape of these studies. This bibliometric and visualized study aimed to delineate research hotspots and trends in the field of CHD genetics. Scientific papers on the genetics of CHD from January 1, 1950, to December 31, 2023, were obtained by searching the Web of Science Core Collection. The bibliometric metadata of each chosen research paper were extracted, analyzed, and visualized using tools such as Microsoft Excel 2021, VOSviewer, and CiteSpace. The final analysis included 5317 papers discussing the genetics of CHD. The countries and journals that published the highest number of papers were the United States (n = 2118), and American Journal of Medical Genetics Part A (n = 332), respectively. In addition to CHD and genetics, keywords such as tetralogy of Fallot, ventricular septal defect, and atrial septal defect appeared most frequently among 8365 keywords. Eight clusters were formed to categorize the keywords. Keywords such as case–control study, whole genome sequencing, and whole exome sequencing in clusters 6, 7, and 8, respectively, had the latest average publication year among all clusters. To the best of our knowledge, this is the first bibliometric analysis of CHD genetics studies. Tetralogy of Fallot, ventricular septal defect, and atrial septal defect are global research topics. The interactions between environmental and genetic factors in the pathogenesis of CHD, genetic etiology of CHD-associated pulmonary arterial hypertension, and molecular genetics of CHD via high-throughput genomic technology are possible areas of future research on the genetics of CHD.
The study was performed in six mohallahs (colonies) of Aligarh City (North India). All six mohallahs are predominantly inhabited by Qureshi (meat sellers, a highly endogamous group) Muslims. A total of 1721 infants and children up to the age of 6 years were examined to determine the incidence of congenital heart diseases (CHD) in relation to the degree of consanguinity of the parents. Around 43% of the subjects were the offspring of consanguineous marriages including second-cousin, first-cousin-once-removed and first-cousin. A higher percentage of CUD was found in the offspring of consanguineous marriages: about 3.37% out of 741 children as compared to 1.22% in 980 offspring of non-consanguineous marriages, whereas in the first-cousin offspring, the percentage of CHD rose to 4.41%. The differences were found to be statistically significant. The present study suggests a genetic influence and also casts doubt on the applicability of a polygenic threshold model to all forms of cardiac malformation.
To determine an accurate estimate of the prevalence of congenital heart defects (CHD) using current standard diagnostic modalities.
We obtained data on infants with CHD delivered during 1998 to 2005 identified by the Metropolitan Atlanta Congenital Defects Program, an active, population-based, birth defects surveillance system. Physiologic shunts in infancy and shunts associated with prematurity were excluded. Selected infant and maternal characteristics of the cases were compared with those of the overall birth cohort.
From 1998 to 2005 there were 398 140 births, of which 3240 infants had CHD, for an overall prevalence of 81.4/10 000 births. The most common CHD were muscular ventricular septal defect, perimembranous ventricular septal defect, and secundum atrial septal defect, with prevalence of 27.5, 10.6, and 10.3/10 000 births, respectively. The prevalence of tetralogy of Fallot, the most common cyanotic CHD, was twice that of transposition of the great arteries (4.7 vs 2.3/10 000 births). Many common CHD were associated with older maternal age and multiple-gestation pregnancy; several were found to vary by sex.
This study, using a standardized cardiac nomenclature and classification, provides current prevalence estimates of the various CHD subtypes. These estimates can be used to assess variations in prevalence across populations, time, or space.
This study determines the prevalence of Congenital Heart Defects (CHD), diagnosed prenatally or in infancy, and fetal and perinatal mortality associated with CHD in Europe.
Data were extracted from the European Surveillance of Congenital Anomalies central database for 29 population-based congenital anomaly registries in 16 European countries covering 3.3 million births during the period 2000 to 2005. CHD cases (n=26 598) comprised live births, fetal deaths from 20 weeks gestation, and terminations of pregnancy for fetal anomaly (TOPFA). The average total prevalence of CHD was 8.0 per 1000 births, and live birth prevalence was 7.2 per 1000 births, varying between countries. The total prevalence of nonchromosomal CHD was 7.0 per 1000 births, of which 3.6% were perinatal deaths, 20% prenatally diagnosed, and 5.6% TOPFA. Severe nonchromosomal CHD (ie, excluding ventricular septal defects, atrial septal defects, and pulmonary valve stenosis) occurred in 2.0 per 1000 births, of which 8.1% were perinatal deaths, 40% were prenatally diagnosed, and 14% were TOPFA (TOPFA range between countries 0% to 32%). Live-born CHD associated with Down syndrome occurred in 0.5 per 1000 births, with > 4-fold variation between countries.
Annually in the European Union, we estimate 36 000 children are live born with CHD and 3000 who are diagnosed with CHD die as a TOFPA, late fetal death, or early neonatal death. Investing in primary prevention and pathogenetic research is essential to reduce this burden, as well as continuing to improve cardiac services from in utero to adulthood.
Congenital heart disease is the most common congenital disorder in newborns. Advances in cardiovascular medicine and surgery have enabled most patients to reach adulthood. Unfortunately, prolonged survival has been achieved at a cost, as many patients suffer late complications, of which heart failure and arrhythmias are the most prominent. Accordingly, these patients need frequent follow-up by physicians with specific knowledge in the field of congenital heart disease. However, planning of care for this population is difficult, because the number of patients currently living with congenital heart disease is difficult to measure. Birth prevalence estimates vary widely according to different studies, and survival rates have not been well recorded. Consequently, the prevalence of congenital heart disease is unclear, with estimates exceeding the number of patients currently seen in cardiology clinics. New developments continue to influence the size of the population of patients with congenital heart disease. Prenatal screening has led to increased rates of termination of pregnancy. Improved management of complications has changed the time and mode of death caused by congenital heart disease. Several genetic and environmental factors have been shown to be involved in the etiology of congenital heart disease, although this knowledge has not yet led to the implementation of preventative measures. In this Review, we give an overview of the etiology, birth prevalence, current prevalence, mortality, and complications of congenital heart disease.
This study sought to characterize temporal trends in all-cause mortality in patients with congenital heart disease (CHD).
Historically, most deaths in patients with CHD occurred in early childhood. Notable advances have since been achieved that may impact on mortality trends.
We conducted a population-based cohort study of patients with CHD in Quebec, Canada, from July 1987 to June 2005. A total of 8,561 deaths occurred in 71,686 patients with CHD followed for 982,363 patient-years.
The proportion of infant and childhood deaths markedly declined from 1987 to 2005, with a reduction in mortality that exceeded that of the general population. Distribution of age at death transitioned from a bimodal to unimodal, albeit skewed, pattern, more closely approximating the general population. Overall, mortality decreased by 31% (mortality rate ratio: 0.69, 95% confidence interval [CI]: 0.61 to 0.79) in the last (2002 to 2005) relative to the first (1987 to 1990) period of observation. Mortality rates decreased in all age groups below 65 years, with the largest reduction in infants (mortality rate ratio: 0.23, 95% CI: 0.12 to 0.47). In adults 18 to 64 years, the mortality reduction (mortality rate ratio: 0.84, 95% CI: 0.73 to 0.97) paralleled the general population. Gains in survival were mostly driven by reduced mortality in severe forms of CHD, particularly in children (mortality rate ratio: 0.33, 95% CI: 0.19 to 0.60), and were consistent across most subtypes.
Deaths in CHD have shifted away from infants and towards adults, with a steady increase in age at death and decreasing mortality.
Congenital heart disease (CHD) afflicts a large number of children every year. The incidence of CHD is generally considered to be 8 per 1,000 live births. However, this estimate is perhaps inaccurate and does not take into consideration regional differences. A large review of the literature was performed to establish the true incidence of CHD and geographical variations. Data on the incidence of specific lesions and their geographical variation, as well as on mortality from CHD, was also reviewed. Taking into consideration the available data on incidence, mortality, and access to care, the global challenge that CHD represents was analyzed. Insight into how to confront this challenge is given.
The aim of this study was to determine the types, patterns, and frequencies of congenital anomalies among newborns of both consanguineous and nonconsanguineous parents in southern Iran. From 9526 consecutive pregnancies observed, 9623 newborns resulted (9431 singleton and 95 sets of multiple gestation). There were 7261 newborns from nonconsanguineous parents and 2362 (24.5%) babies from consanguineous marriages. Of the total pregnancies, 1.54% resulted in malformed children (1.53% of singleton and 2.1% of multiple gestations). The incidence of congenital abnormalities in newborns of nonconsanguineous parents was 1.66% as compared to 4.02% for newborns of the consanguineous group. Major and multiple malformations were found to be slightly more common in the consanguinous group. Prematurity, prenatal mortality rate, and congenital abnormalities were more common in the consanguineous group. Probably the closer the familial relationship of the parents, the greater the chances of congenital abnormalities.
Since more and more women in developed countries are delaying childbearing to an older age, it is important to find out whether birth defects, other than those resulting from chromosomal anomalies, are related to maternal age. We have studied all 26,859 children with birth defects of unknown aetiology identified among 576,815 consecutive livebirths in British Columbia. All these cases' records were linked with provincial birth records to allow determination of maternal age at birth. We excluded children with chromosomal anomalies and those with other birth defects of known aetiology. Only 3 of the 43 birth defect categories studied showed significant maternal-age-specific trends: there were decreasing linear trends with maternal age for patent ductus arteriosus (chi 2 = 36.65, 1 df, p less than 0.01) and hypertrophic pyloric stenosis (chi 2 = 4.90, 1 df, p less than 0.05) and a bell-shaped curve (risk increasing to maternal age 30 then falling) for congenital dislocatable hip/hip click. The findings from this population-based analysis of no association between the incidence of birth defects of unknown aetiology and advancing maternal age should be reassuring to healthy women who opt to delay childbearing.
Cardiovascular malformations were examined for white/black variation in the Baltimore-Washington Infant Study. In this population-based case-control study, cases (n = 2,087) were live births with cardiovascular malformations ascertained through pediatric cardiology centers and 53 hospitals in Maryland, the District of Columbia, and northern Virginia between 1981 and 1987. Controls (n = 2,721) were a random sample of infants from the live-birth cohort that gave rise to the cases. The proportion of infants that were white was similar for all cases as a group and controls (0.68 and 0.67, respectively). Subgroup analysis, however, revealed an excess of white infants among cases with Ebstein's anomaly (odds ratio (OR) = 3.7, 95% confidence interval (Cl) 1.1-12.5), aortic stenosis (OR = 3.6, 95% Cl 1.7-7.6), pulmonary atresia (OR = 2.5, 95% Cl 1.0-6.1), coarctation of the aorta (OR = 2.2, 95% Cl 1.4-3.5), and D-transposition of the great arteries (OR = 1.6, 95% Cl 1.1-2.5), and a deficit of white infants among cases with pulmonary stenosis (OR = 0.6, 95% Cl 0.4-0.8) and heterotaxia (OR = 0.4, 95% Cl 0.3-0.8). These associations remained when cases were stratified by infant's age or by method of diagnosis. Controlling for socioeconomic factors attenuated the white excess for Ebstein's anomaly (OR = 3.0, 95% Cl 0.9-10.5), disclosed a white excess among cases of L-transposition of the great arteries (OR = 2.8, 95% Cl 1.0-8.0), and revealed that the white excess for aortic stenosis was limited to low and middle socioeconomic strata. These results highlight racial variations in cardiovascular malformations, suggest that socioeconomic factors account for some of this variation, and identify malformation subgroups for which further evaluation of sociocultural, environmental, and familial factors is needed.
The Baltimore-Washington Infant Study is a regional epidemiologic study of congenital heart disease. Among Infants born in the study area in 1981 and 1982, 664 had a diagnosis of congenital heart disease confirmed in the first year of life by echocardiography, cardiac catheterization, cardiac surgery, or autopsy. The prevalence rate was 3.7/1,000 livebirths for all cases and 2.4/1,000 livebirths for cases confirmed by invasive methods only. Diagnosis-specific prevalence rates of congenital heart disease are compared with those of eight previous case series. Changing diagnostic categorizations in the time span covered and methodological differences resulted in great variation of the data. However, the data of the New England Infant Cardiac Program which used the same case discovery methods showed similar occurrences of major morphologic abnormalities, suggesting that these are stable basic estimates in the eastern United States. For all case series, the rate of confirmed congenital heart disease was approximately 4/1,000 livebirths over the 40-year time span.
Within a prospective study of 56,109 total births, 457 youngsters have been found to have congenital heart disease. The overall incidence is 8.14/1000 total births, 8.0/1000 for the Negro and 8.3/1000 for the white. A specific lesion has been identified for each patient and lesion frequencies given for each class of patient, stillbirth, neonatal death, infant death, childhood death, and survivors. The percentage of autopsies was 93% in the stillbirths, 89% in the neonatal deaths, and 76% for those dying after 28 days of age. Of those classified as having definite congenital heart disease, 93% have been examined by a pediatric cardiologist. The average follow-up time for the 272 survivors is 3 years. Thirty-five per cent of patients with ventricular septal defect surviving more than 6 months had their lesion close spontaneously; one-half of the survivors with tetralogy of Fallot were "atypical," and essentially equal numbers of blacks and whites had all types of coarctation of the aorta in line with the study population, which is 47% black and 53% white.
The incidence of congenital heart disease (CHD) in the Western industrialized world has varied from a low value of about 3 to 5 per 1000 live births to about 12 per 1000 live births. Most of the lower incidence figures were obtained before there were sufficiently well trained pediatric cardiologists and before the success of cardiac surgery put a premium on early and correct diagnosis of CHD. The advent of echocardiography with Doppler color flow measurements has made it possible to diagnose lesions that are asymptomatic, minor, and even without murmurs. Given these differences, there does not appear to have been a significant increase in the incidence of CHD over the last 20-30 years. The incidence of CHD in underdeveloped countries is not known, but the distribution of different lesions is fairly similar to those in developed countries except perhaps for fewer with aortic stenosis and coarctation of the aorta.
Racial group studies have identified differences in the occurrence of congenital heart disease (CHD) among ethnic populations. The aim of this study was to characterize the proportionate frequency and clinical profile of children with symptomatic cardiac abnormalities in Hong Kong. The hospital records of 666, mainly Southern Chinese children with symptomatic CHD, who were 4 years of age or younger and who were admitted to Grantham Hospital, Hong Kong, in 1994 and 1995 were analyzed retrospectively. Left-to-right shunting (45.0%) and pulmonary outflow obstruction (34.4%) were the most frequently diagnosed categories, followed by left ventricular outflow obstruction (8.3%), transposition of the great arteries (4.2%), conditions with intracardiac mixing (3.9%), and other cardiac lesions (4.2%). Compared with Western studies, pulmonary outflow obstruction (p<0.0001), particularly tetralogy of Fallot and critical pulmonary stenosis, were more frequent in Chinese children. In contrast with previous reports, coarctation of the aorta (5%) does not seem to be uncommon in Chinese patients. Conversely, aortic stenosis and hypoplastic left ventricle may be rare in these children (1% vs 3% and 3-7%). Other cardiac lesions showed no consistent racial difference in the frequency of occurrence. Chinese patients with Down's syndrome had ventricular septal defect (38%) as the predominant lesion followed by atrioventricular septal defect (25%). Western studies usually report a reverse pattern for these two lesions. The mortality rate for the total cohort was 7.5%. However, of those with conditions with intracardiac mixing and left ventricular outflow tract obstruction many did not survive childhood (20% and 21%, respectively).
A new medical community, the grown-up congenital heart patients--GUCH--has resulted from successes of cardiac surgery over 30-40 years. Many survivors have complicated problems, medical and surgical, demanding experience and expertise neither provided nor organised in most countries. Islands of good care exist with difficulty. The experience of one specialist GUCH unit established for 25 years shows that 55-60% admissions are for complex lesions, particularly after complicated surgery. The patients' overall costs are at least twice those of other cardiac patients. GUCH admissions are about 5-8% of the total, varying according to the population/region served. Supervised medical care for GUCH is equally important in outpatient services, involving 3 times the secretarial time of other cardiac patients, an accessible database and a "helpline" for doctors and patients. This may be life-saving in patients with complex conditions. The GUCH population is ageing, with increasing numbers of complex patients. 30% of admissions now are over 40 years old, and 5% are over 60, confirming that this is an adult medical speciality, not paediatric. Invasive investigations and arrhythmias provide the most frequent reasons for admissions--atrial flutter is the commonest arrhythmia, needing experts when it occurs in Fontan, transposition, etc. Routine coronary arteriography is also important. In cardiac surgery, one in five admissions presents organisational problems. Reoperation, now as many as 9 or 10 times, has to be optimised. Reoperation on left and right outflow tracts-for changing valves and conduits--is more common than first operations. GUCH patients represent a relatively small portion of the whole population. Such patients in a population of 7-8 million need to be concentrated in 1-2 centres, depending on culture, religion, geography, language etc., to provide necessary experience, expertise and education.
As part of a study on the effects of in-utero cocaine exposure on the heart. a cohort of 104 full-term, healthy infants who did not have intrauterine drug exposure underwent extensive echocardiographic examination at birth and at 2 to 6 months of age. These studies were evaluated for the presence of a patent ductus arteriosus (PDA) and patent foramen ovale (PFO). Infants were eligible for the study if they were <72 hours old, weighed >1,500 g, and were between 33 and 42 weeks gestation. In all, 64 infants were excluded from the study because of various maternal and neonatal causes. We excluded infants born to mothers who used medications during pregnancy, such as bronchodilators, that may have affected the cardiovascular system. We also excluded infants of mothers with acute or chronic diseases such as systemic hypertension, hepatitis, diabetes mellitus, sepsis, and human immunodeficiency virus infection, symptomatic infants who required administration of oxygen beyond 5 minutes, ventilatory support, or admission to neonatal intensive care unit; and newborns with associated congenital anomalies including cardiac defects (except PDA, PFO, or physiologic mitral, tricuspid, or pulmonary regurgitation).
This study was designed to determine the reasons for the variability of the incidence of congenital heart disease (CHD), estimate its true value and provide data about the incidence of specific major forms of CHD. The incidence of CHD in different studies varies from about 4/1,000 to 50/1,000 live births. The relative frequency of different major forms of CHD also differs greatly from study to study. In addition, another 20/1,000 live births have bicuspid aortic valves, isolated anomalous lobar pulmonary veins or a silent patent ductus arteriosus. The incidences reported in 62 studies published after 1955 were examined. Attention was paid to the ways in which the studies were conducted, with special reference to the increased use of echocardiography in the neonatal nursery. The total incidence of CHD was related to the relative frequency of ventricular septal defects (VSDs), the most common type of CHD. The incidences of individual major forms of CHD were determined from 44 studies. The incidence of CHD depends primarily on the number of small VSDs included in the series, and this number in turn depends upon how early the diagnosis is made. If major forms of CHD are stratified into trivial, moderate and severe categories, the variation in incidence depends mainly on the number of trivial lesions included. The incidence of moderate and severe forms of CHD is about 6/1,000 live births (19/1,000 live births if the potentially serious bicuspid aortic valve is included), and of all forms increases to 75/1,000 live births if tiny muscular VSDs present at birth and other trivial lesions are included. Given the causes of variation, there is no evidence for differences in incidence in different countries or times.
Following a brief review of the development of medical ultrasonics from the mid-1930s to the mid-1950s, the collaboration between Edler and Hertz that began in Lund in 1953 is described. Using an industrial ultrasonic flaw detector, they obtained time-varying echoes transcutaneously from within the heart. The first clinical applications of M-mode echocardiography were concerned with the assessment of the mitral valve from the shapes of the corresponding waveforms. Subsequently, the various M-mode recordings were related to their anatomical origins. The method then became established as a diagnostic tool and was taken up by investigators outside Lund, initially in China, Germany, Japan and the USA and, subsequently, world-wide. The diffusion of echocardiography into clinical practice depended on the timely commercial availability of suitable equipment. The discovery of contrast echocardiography in the late 1960s further validated the technique and extended the range of applications. Two-dimensional echocardiography was first demonstrated in the late 1950s, with real-time mechanical systems and, in the early 1960s, with intracardiac probes. Transesophageal echocardiography followed, in the late 1960s. Stop-action two-dimensional echocardiography enjoyed a brief vogue in the early 1970s. It was, however, the demonstration by Bom in Rotterdam of real-time two-dimensional echocardiography using a linear transducer array that revolutionized and popularized the subject. Then, the phased array sector scanner, which had been demonstrated in the late 1960s by Somer in Utrecht, was applied to cardiac studies from the mid-1970s onwards. Satomura had demonstrated the use of the ultrasonic Doppler effect to detect tissue motion in Osaka in the mid-1950s and the technique was soon afterwards applied in the heart, often in combination with M-mode recording. The development of the pulsed Doppler method in the late 1960s opened up new opportunities for clinical innovation. The review ends with a mention of color Doppler echocardiography. (E-mail:
Researchers and other public health professionals continue to debate the use of prevalence versus incidence as the preferred term to represent the frequency of birth defects. This paper addresses this question by noting that incidence--the number of new cases of a disorder in a given at-risk population during a specified time period--cannot be reliably estimated with existing data. Consequently, it is not appropriate to use the term "incidence" in reporting the frequency of birth defects, and the term prevalence is recommended. The basis for this recommendation, and issues involved in calculating both measures, are discussed.
Fetal echocardiography allows for early detection of congenital heart disease, and pregnancy termination may be an option in cases of complex defects. In the current study, the most important factors contributing to the diagnosis and termination of affected pregnancies are reviewed and their combined effect on the future prevalence of liveborn congenital heart disease is evaluated. The relative reduction of the prevalence of the most severe forms of congenital heart disease is estimated as the product of the probability that (1) a fetal cardiac screening is performed (p
evaluation), (2) an affected pregnancy is detected (P
detection), (3) pregnancy termination is decided following antenatal diagnosis (P
decision). In areas where termination of pregnancy is a realistic and supported option, a universal sonographic screening of all pregnancies (P
evaluation = 1), with an average reported sensitivity of 35% and a termination rate of 43% following antenatal diagnosis, would result in a 15% overall reduction of the prevalence of the most severe forms of congenital heart disease. However, wide variability exists regarding the defect-specific estimates (2–50% prevalence relative reduction) due to considerable differences in the reported diagnostic sensitivity and termination rates associated with each heart defect. If an earlier diagnosis could be achieved, which is reported to be associated with an average 1.4-fold increased probability of termination, the overall reduction of the prevalence of congenital heart disease could approach 21%. As the skills of obstetric and pediatric cardiology sonographers improve, fetal echocardiography is expected to have a substantial impact on the future epidemiology of liveborn congenital heart disease.
Prevention of congenital cardiovascular defects has been hampered by a lack of information about modifiable risk factors for abnormalities in cardiac development. Over the past decade, there have been major breakthroughs in the understanding of inherited causes of congenital heart disease, including the identification of specific genetic abnormalities for some types of malformations. Although relatively less information has been available on noninherited modifiable factors that may have an adverse effect on the fetal heart, there is a growing body of epidemiological literature on this topic. This statement summarizes the currently available literature on potential fetal exposures that might alter risk for cardiovascular defects. Information is summarized for periconceptional multivitamin or folic acid intake, which may reduce the risk of cardiac disease in the fetus, and for additional types of potential exposures that may increase the risk, including maternal illnesses, maternal therapeutic and nontherapeutic drug exposures, environmental exposures, and paternal exposures. Information is highlighted regarding definitive risk factors such as maternal rubella; phenylketonuria; pregestational diabetes; exposure to thalidomide, vitamin A cogeners, or retinoids; and indomethacin tocolysis. Caveats regarding interpretation of possible exposure-outcome relationships from case-control studies are given because this type of study has provided most of the available information. Guidelines for prospective parents that could reduce the likelihood that their child will have a major cardiac malformation are given. Issues related to pregnancy monitoring are discussed. Knowledge gaps and future sources of new information on risk factors are described.
for the European Surveillance of Congenital Anomalies (EUROCAT) Working Group. Congenital heart defects in Europe: prevalence and perinatal mortality
- H Dolk
- M Loane
- Garne
Dolk H, Loane M, Garne E, for the European Surveillance of Congenital Anomalies (EUROCAT) Working Group. Congenital heart defects in Europe: prevalence and perinatal mortality, 2000 to 2005. Circulation 2011;123:841–9.
- Van Der Linde
JACC Vol. 58, No. 21, 2011
van der Linde et al.
November 15, 2011:2241–7
Birth Prevalence of Congenital Heart Disease