Congenital heart disease is the most common congenital anomaly, occurring in almost 1% of live births (1). Among birth defects, congenital heart disease is the leading cause of infant mortality.

The most common congenital heart diseases diagnosed in infancy are muscular and perimembranous ventricular septal defectsfollowed by secundum atrial septal defects, with a total prevalence of 48.4 in 10,000 live births. The most common cyanotic congenital heart disease is tetralogy of Fallot, which is twice as prevalent as transposition of the great arteries (4.7 vs. 2.3/10 000 births).

General reference

  • 1. Reller MD, Strickland MJ, Riehle-Colarusso T, et al: Prevalence of congenital heart defects in metropolitan Atlanta, 1998–2005. J Pediatr 153(6):807–813, 2008.


Environmental and genetic factors contribute to the development of congenital heart disease.

Common environmental factors include maternal illness (eg, diabetes, rubella, systemic lupus erythematosus) or maternal intake of teratogenic agents (eg, lithiumisotretinoin, anticonvulsants). Maternal age is a known risk factor for certain genetic conditions, especially Down syndrome, that may include cardiac defects. It is unclear whether maternal age is an independent risk factor for congenital heart disease. Paternal age may also be a risk factor (1).

Certain numerical chromosomal abnormalities (aneuploidies), such as trisomy 21 (Down syndrome), trisomy 18, trisomy 13, and monosomy X (Turner syndrome), are strongly associated with congenital heart disease. However, these abnormalities account for only 5 to 6% of patients with congenital heart disease.

Many other cases involve subchromosomal deletions (microdeletions), subchromosomal duplications, or single-gene mutations. Often, these mutations cause congenital syndromes affecting multiple organs in addition to the heart. Examples include DiGeorge syndrome (microdeletion in 22q11.2) and Williams-Beuren syndrome (microdeletion in 7p11.23). Single-gene defects that cause syndromes associated with congenital heart disease include mutations in fibrillin-1 (Marfan syndrome), TXB5 (Holt-Oram syndrome), and possibly PTPN11 (Noonan syndrome). Single-gene defects can also cause isolated (ie, nonsyndromic) congenital heart defects.

In about 72% of patients with congenital heart disease, there is no identifiable genetic etiology (2).

The recurrence risk of congenital heart disease in a family varies depending on the cause. Risk is negligible in de novo mutations, 2 to 5% in nonsyndromic multifactorial congenital heart disease, and 50% when an autosomal dominant mutation is the cause. It is important to identify genetic factors because more patients with congenital heart disease are surviving into adulthood and potentially starting families.

Etiology references

  • 1. Materna-Kiryluk A, Wiśniewska K, Badura-Stronka M, et al: Parental age as a risk factor for isolated congenital malformations in a Polish population. Paediatr Perinat Epidemiol 23(1):29-40, 2009. doi: 10.1111/j.1365-3016. 2008.00979.x.

  • 2. Russell MW, Chung WK, Kaltman JR, Miller TA: Advances in the understanding of the genetic determinants of congenital heart disease and their impact on clinical outcomes. J Am Heart Assoc 7(6):e006906, 2018. doi:10.1161/JAHA.117.006906.

Normal Fetal Circulation

Fetal circulation is marked by

  • Right-to-left shunting of blood around the unventilated lungs through a patent ductus arteriosus (connecting the pulmonary artery to the aorta) and foramen ovale (connecting the right and left atria)

Shunting is encouraged by high pulmonary arteriolar resistance and relatively low resistance to blood flow in the systemic (including placental) circulation. About 90 to 95% of the right heart output bypasses the lungs and goes directly to the systemic circulation. The fetal ductus arteriosus is kept open by low fetal systemic Pao2 (about 25 mm Hg) along with locally produced prostaglandins. The foramen ovale is kept open by differences in atrial pressures: left atrial pressure is relatively low because little blood is returned from the lungs, but right atrial pressure is relatively high because large volumes of blood return from the placenta.