Congenital heart diseases (CHDs) arise from incomplete development and formation of the cardiovascular system during fetal life. They are not always diagnosed at birth and may remain undetected, particularly in their milder forms.
Prevalence of Congenital Heart Disease Across Different Age Groups
The prevalence of CHDs in each age group depends partly on the detection method used (clinical examination or imaging techniques), but primarily on the survival probability of affected individuals from one age group to the next.
CHDs are already present upon completion of cardiovascular system development during the first trimester of pregnancy. Their prevalence during fetal life depends on the ability to detect them through prenatal screening. At the same time, because fetuses affected by CHD frequently have chromosomal abnormalities or malformations involving other organ systems, a proportion will not survive to delivery due to spontaneous miscarriage (common in fetuses with chromosomal abnormalities) or intrauterine death.
Consequently, the frequency of CHDs that could theoretically be identified during fetal life under ideal diagnostic imaging conditions is significantly higher than that observed during infancy. If the possibility of human intervention in this natural course, in the form of pregnancy termination, is also taken into account, the likelihood of detecting CHDs during fetal life increases even further.
According to published studies, the prevalence of CHDs is estimated at 5–8 cases per 1,000 live births. Considering that mild forms of CHD may remain undiagnosed, it may be assumed that the probability of CHD in a newborn could be as high as 1 in 100. Approximately one-quarter of these cases represent severe forms of CHD requiring surgical intervention during the neonatal or infant period.
Prevalence of Specific Forms of Congenital Heart Disease
The prevalence of CHDs, as well as that of individual cardiac defects, depends on the detection method used (clinical examination, ultrasonography, etc.) and on the age at which evaluation is performed (fetal, neonatal, childhood, or adulthood).
According to one of the earliest epidemiological studies of congenital heart disease, conducted during the period when echocardiographic diagnosis became widely available (Baltimore-Washington Infant Study, 1981–1989), the most common forms of CHD (diagnoses per 10,000 live births) were:
- Ventricular Septal Defect (VSD) (15%) – most commonly the perimembranous type
- Pulmonary Atresia (5.8% )
- Pulmonary Valve Stenosis (3.8%)
- Tricuspid Atresia (3.6%)
- Atrioventricular Septal Defect (AVSD), particularly in association with Trisomy 21 (3.3 %)
- Transposition of the Great Arteries (TGA) (2.6%)
- Tetralogy of Fallot (TOF) (2.6 %)
- Atrial Septal Defect (ASD) (2.3 %)
- Hypoplastic Left Heart Syndrome (HLHS) (1.8 %)
- Coarctation of the Aorta (CoA) (1.4 %)
- Isomerism Syndromes (1.4 %)
- Patent Ductus Arteriosus (PDA) (0.8 %)
- Aortic Valve Stenosis (0.8 %)
- Common Arterial Trunk (Truncus Arteriosus) (0.7 %)
- Double Outlet Right Ventricle (DORV) (0.5 %)
- Ebstein Anomaly (0.5 %)
Prenatal Diagnosis and the Epidemiology of Congenital Heart Disease
The epidemiology of CHDs (overall and disease-specific prevalence) depends both on the survival probability of affected individuals from one age group to the next and on the likelihood of detecting subclinical forms of each condition.
Advances in pediatric cardiac surgery have dramatically improved the survival of even the most severe neonatal congenital heart defects. As a result, virtually no form of CHD is now considered incompatible with life. Following birth, every diagnosed CHD is expected to have a significantly improved prognosis due to modern therapeutic interventions compared with the natural history of the disease. Consequently, an increasing population of older children and adults with a history of congenital heart disease is expected in the future.
The impact of prenatal diagnosis on the epidemiology of fetal CHDs is more complex and is characterized by two opposing effects. Prenatal diagnosis contributes both to an increase and to a decrease in the survival probability of affected fetuses, with the overall effect representing the balance between these opposing influences.
The positive effect on survival is due not so much to the possibility of prenatal surgical correction—which remains largely investigational—but rather to the awareness of the cardiac defect before birth and the corresponding preparation for immediate neonatal management. Such preparation may include delivery near a specialized cardiac surgery center, prompt access to surgical intervention, and prevention of complications associated with delayed diagnosis, such as hypoxia, acidosis, and injury to vital organs.
The negative effect on survival results from the possibility that families may choose termination of pregnancy when severe congenital heart disease is diagnosed, particularly when it is associated with additional malformations or genetic syndromes.
Based on a simple mathematical model and the current sensitivity of prenatal diagnosis, a reduction of approximately 15% in the number of live births affected by CHD is expected as a consequence of prenatal detection. In cases where diagnosis is established at an earlier gestational age—thereby increasing the likelihood of a decision for pregnancy termination by approximately 40%—the reduction may reach 21%.
Heredity of Congenital Heart Disease
Are congenital heart diseases hereditary?
The answer is that most CHDs are considered multifactorial disorders, with an unknown etiology in up to 85% of cases, most likely resulting from interactions between genetic and environmental factors.
However, in approximately 10% of cases, CHDs are associated with chromosomal abnormalities or single-gene disorders in the affected individual, such as Trisomy 21 (Down syndrome), DiGeorge syndrome, and others. In addition, known teratogenic factors, including certain medications and viral infections during pregnancy, account for a small proportion of congenital heart defects.
The influence of heredity on the likelihood that a child (or fetus) will develop CHD is significant when a first-degree relative is affected, as this risk exceeds the baseline risk in the general population, which is estimated to be up to 1%.
Numerous studies have demonstrated a higher recurrence risk of CHD in offspring when the affected first-degree relative is the mother (risk >3%), compared with an affected father or sibling (risk 1–3%).
Furthermore, specific forms of CHD exhibit a higher hereditary tendency than others. The risk is particularly elevated in children of mothers affected by aortic valve stenosis, atrioventricular septal defect, or Tetralogy of Fallot (>10%). A lower risk of CHD (2–3%) is observed in children who have siblings affected by ventricular septal defect, atrial septal defect, patent ductus arteriosus, or Tetralogy of Fallot.
The following tables present the probability of congenital heart disease in a child according to the presence of congenital heart disease in the parents (mother or father) and siblings.
| Parental Congenital Heart Disease | Risk of CHD in the Child (%) if Mother is Affected / if Father is Affected |
|---|---|
| Aortic Valve Stenosis | 18 / 3 |
| Atrioventricular Septal Defect (AVSD) | 14 / 1 |
| Tetralogy of Fallot (TOF) | 10 / 1.5 |
| Ventricular Septal Defect (VSD) | 6 / 2 |
| Pulmonary Valve Stenosis | 4 / 2 |
| Coarctation of the Aorta (CoA), Patent Ductus Arteriosus (PDA) | 4 / 2 |
Table 1. Probability of congenital heart disease (CHD) in the offspring of parents affected by congenital heart disease.
| Congenital Heart Disease in a Sibling | Risk of CHD in the Child (%) |
|---|---|
| Ventricular Septal Defect (VSD), Patent Ductus Arteriosus (PDA) | 3.0 |
| Tetralogy of Fallot (TOF), Atrial Septal Defect (ASD) | 2.5 |
| Aortic Valve Stenosis, Pulmonary Valve Stenosis, Coarctation of the Aorta (CoA) | 2.0 |
| Atrioventricular Septal Defect (AVSD), Hypoplastic Left Heart Syndrome (HLHS) | 2.0 |
| Transposition of the Great Arteries (TGA) | 1.5 |
| Tricuspid Atresia, Pulmonary Atresia, Truncus Arteriosus, Ebstein Anomaly | 1.0 |
Table 2. Risk of Congenital Heart Disease in a Child When a Sibling is affected by CHD
Genetic Syndromes and Congenital Heart Disease
The association between congenital heart diseases (CHDs) and genetic syndromes related to chromosomal or genetic abnormalities, as well as with the coexistence of specific malformations (associations), is particularly strong. At least 10% of CHDs diagnosed in newborns and an even higher proportion (up to 30%) diagnosed in fetuses are associated with chromosomal or genetic abnormalities. The higher likelihood of detecting chromosomal abnormalities during fetal life compared with the neonatal period is attributable to the increased risk of intrauterine death among fetuses carrying chromosomal abnormalities.
This association is so strong that the diagnosis of a CHD during fetal life constitutes an indication for fetal karyotype analysis to exclude an associated chromosomal abnormality, particularly when the cardiac defect coexists with structural anomalies involving other organ systems. Furthermore, specific forms of CHD are more strongly associated with particular chromosomal abnormalities, such as atrioventricular septal defect (AVSD) with Trisomy 21 and coarctation of the aorta (CoA) with Turner syndrome.
Since certain genetic mutations can only be detected using specialized techniques (e.g., FISH analysis), it is particularly important to request targeted genetic testing for syndromes associated with specific forms of CHD. Typical examples include the association between conotruncal abnormalities (e.g., truncus arteriosus) and DiGeorge syndrome, supravalvular aortic stenosis and peripheral pulmonary artery stenosis with Williams syndrome, and dysplastic pulmonary valve associated with left ventricular hypertrophy in Noonan syndrome.
Therefore, evaluation by a clinical geneticist is particularly important for children with CHD, especially when they present with distinctive phenotypic features suggestive of a genetic syndrome, growth abnormalities, learning difficulties, or behavioral problems.
The following tables summarize the prevalence of CHD in chromosomal syndromes, single-gene disorders, and multiple malformation associations, as well as the most common cardiac defects encountered in each condition.
| Chromosomal Syndrome | Probability of CHD | Common Forms of CHD |
|---|---|---|
| Trisomy 21 (Down Syndrome) | 50% | Atrioventricular Septal Defect (AVSD), Ventricular Septal Defect (VSD) |
| Trisomy 13 (Patau Syndrome) | 80% | Atrioventricular Septal Defect (AVSD), Ventricular Septal Defect (VSD), Tetralogy of Fallot (TOF) |
| Trisomy 18 (Edwards Syndrome) | 100% | Atrioventricular Septal Defect (AVSD), Ventricular Septal Defect (VSD), Double Outlet Right Ventricle (DORV) |
| Turner Syndrome | 35% | Aortic Valve Stenosis (AoS), Coarctation of the Aorta (CoA) |
| Klinefelter Syndrome | 50% | Mitral Valve Prolapse (MVP) |
| Fragile X Syndrome | 70% | Mitral Valve Prolapse (MVP) |