Prenatal Diagnosis of Congenital Heart Disease

Introduction

Congenital heart disease (CHD) affects 6-8 per 1000 live births. However, only 20% of babies with congenital heart disease would be identified if the examination of the fetal heart were confined to traditional high-risk groups such as increased nuchal translucency, family history of CHD, and teratogen exposure.

The current American Society of Echocardiography guidelines suggest the optimal timing for performance of a comprehensive transabdominal fetal echocardiogram is between 18-22 weeks' gestation. Repeat fetal echocardiograms are suggested for those fetuses identified with diseases that can be progressive, a suboptimal scan, or any patient with fetal arrhythmia. The interpreting physician must be able to recognize the full spectrum of simple and complex acquired and congenital heart disease and its manifestations and natural history throughout gestation. This includes knowledge of the principles of biologic ultrasound instrumentation; understanding of maternal–fetal physiology; familiarity with the latest developments in obstetric diagnostics; and knowledge of the growing field of invasive fetal intervention. It is important to recognize the limitations of fetal echocardiography in detecting important associated lesions and to have the skill to apply all modalities of echocardiography including two-dimensional, M-mode, pulsed-wave, continuous wave, and Doppler color flow mapping in recognizing and evaluating both the normal and abnormal fetal anatomy and physiology throughout the stages of human heart development. There should also be a thorough understanding of fetal arrhythmias and a team readily available to further aid in the diagnosis and treatment of dysrhythmias.

Historical Perspective

The first real-time cardiac heart images and quantitative data were published by the Lange, Sahn, and Reed group in Tucson, Arizona, in 1980. Lindsey Allan published echocardiogram/anatomical correlates in the same year describing systematically real-time normal and abnormal ultrasonic anatomy of the fetal heart, laying the foundation for the field of fetal echocardiography. Using ultrasonic equipment available at the time, real-time, cross-sectional study and diagnosis of fetal cardiac anomalies in utero in the second trimester was possible.

Improvements in diagnostic capabilities over the past 40 years have had tremendous impact on fetal cardiac diagnosis. The use of direct Doppler interrogation of fetal intracardiac flow was first demonstrated in 1985. Use of Doppler color flow mapping in the assessment of fetal cardiac malformations and particularly in a screening situation was started shortly after. The use of color Doppler has become indispensable in the diagnosis of more complicated cardiac malformations. By the late 1990s, the diagnostic accuracy of the nature of complex cardiac malformations in utero was as high as 95%.

Overview of Fetal Circulation and Cardiac Adaptation at Birth

One must not assume that the fully developed fetal heart is analogous to the infant or child heart. This section discusses the difference between the fetal myocardium and the postnatal myocardium and unique fetal blood flow through naturally occurring shunts, blood flow to the placenta, and pulmonary blood flow.

The fetal myocardium has significant differences from the pediatric and adult myocardium. It is composed of a greater proportion of noncontractile elements (60% versus 30%), and fetal cardiomyocytes can divide, whereas adult cardiomyocytes can only hypertrophy. In addition, the removal of calcium from troponin C is slower in the fetus, resulting in slower muscle relaxation. The right ventricle handles more volume, its radius is greater, the radius-to-wall thickness is greater, and it hypertrophies to maintain appropriate wall tension. As a result, the wall thickness of the right ventricle is approximately equal to that of the left in fetal life.

These differences result in increased stiffness and impaired relaxation of the fetal heart as demonstrated in the Doppler pattern across the atrioventricular (AV) valves. In the fetus, passive ventricular filling is impaired, and active atrial filling is responsible for emptying the atria. As a result, the right ventricle is more sensitive to changes in preload and shows signs of dysfunction before the left ventricle. Increased preload, as seen in anemia, viral illness, and significant arterial to venous malformations (AVMs) results in fetal hydrops. There is a gradual change from the “fetal heart” to an “adult heart” that progresses throughout the neonatal period to adulthood. These changes can be easily demonstrated by echocardiography.

The fetus has a unique physiology consisting of various shunts to promote oxygenated blood to the brain and deoxygenated blood to the placenta. The foramen ovale is designed to allow higher oxygenated blood from the placental veins preferentially to the left atrium. The increased oxygenated blood from the placenta travels through the umbilical vein to the ductus venosus. The blood then travels to the inferior vena cava (IVC) and is directed across the foramen ovale by the Eustachian valve. Lower oxygenated blood flow from the fetal brain is preferentially directed from the superior vena cava (SVC) to the right ventricle and eventually across the ductus arteriosus to the placenta. The ductus arteriosus is responsible for carrying most of the cardiac output from the “pulmonary circulation” to the descending aorta and the placenta. The flow pattern is typically a predominant systolic peak with continuous low-velocity diastolic flow. Continuous diastolic flow toward the descending aorta is a result of low-resistance placental circulation. Elevated diastolic flow in the ductus arteriosus is a sign of ductal constriction or lower body arteriovenous malformations. The aortic isthmus has a distinctive wave form in the fetus. The aortic isthmus is located between the left subclavian artery and the insertion of the ductus arteriosus. It is unique in that it straddles two different output systems (the “systemic” output of the left ventricle and the “pulmonic” output of the right ventricle that is directed toward the placenta). Flow is normally toward the placenta in both systole and diastole at the level of the aortic isthmus. Decreased flow in the aortic isthmus from inappropriate shunting can result in isthmus hypoplasia and eventually coarctation of the aorta. Left ventricular outflow tract obstruction or significant left ventricular dysfunction results in reversal of flow toward the head in systole. Reversal of flow may also be seen in decreased upper body vascular resistance (AVMs or stressed fetus).

The circulation to the fetal lungs is uniquely different than the blood flow in the adult. The size and number of pulmonary arteries and veins increase as gestation advances. From 20-30 weeks’ gestation, blood flow to the lung increases from 15%-25% of the combined cardiac output, accompanied with a significant decrease in weight-indexed pulmonary vascular resistance (PVR). In the animal lab, increasing oxygen tension from 24-46 mm Hg increases pulmonary blood flow by tenfold in term lambs. This suggests that a substantial portion of the high PVR in the mature fetus is maintained by vasoconstriction in an oxygen tension-sensitive manner. Increased oxygen tension in lesions such as transposition of the great arteries may explain development of foramen ovale restriction or closure in the neonatal period. Increased pulmonary blood flow results in increased venous return to the left atrium, resulting in increased left atrial pressure and potential restriction at the foramen ovale.

There is a transition between fetal life and infancy during the first few hours in which the pulmonary vascular resistance decreases, resulting in increased pulmonary blood flow. It results from various birth-related events that occur concurrently and sequentially, which include ventilation, oxygenation, increasing shear stress of blood flow, and changes in the activities of a number of vasoactive agents and their signaling pathways, such as EDNO, PGI2, endothelin-1 (ET-1), and PAF. However, in certain cases, the maturation of the pulmonary vascular bed is delayed, which results in persistent pulmonary hypertension of the newborn (PPHN). Understanding the transition period between fetal circulation and infant circulation is critically important in certain types of congenital heart disease, especially ductal dependent lesions.

A major difference in the fetal circulation compared with the postnatal circulation is the inclusion of the placental circulation. Typically, the placenta is a low-resistance circuit. The umbilical arterial flow is in part dependent on the placental resistance. The placenta has the lowest vascular resistance of any structure in the fetal circulation and, therefore, is the major contributor to umbilical arterial flow. The two vessels that arise from the iliac artery and travel to the placenta carry a large amount of blood. The pulsatility is low and progressively decreases during pregnancy. Reversal of diastolic flow indicates flow toward other vascular regions in fetus where resistance is low, such as an AVM or severe elevation in placental resistance. The ductus venosus connects the umbilical vein with the inferior vena cava (IVC) as it enters the right atrium (RA). Flow is generally phasic in the IVC toward the heart. Phasic periods with absent forward flow or reversal of flow are markers of impaired relaxation of the right ventricle or right atrium secondary to decreased compliance. This can be the result of a cardiomyopathy, ductal restriction, and/or severe volume overload.

Indications for Fetal Echocardiogram

Indications for a fetal echocardiogram fall within three categories that are listed in Table 73.1 with examples from each category. However, if all high-risk fetuses meeting the recommended indications have a fetal echocardiogram performed, only 20% of CHD will be detected. Recent data demonstrates that only 48%-60% of congenital heart defects are detected prenatally. Detection rates are poorest in rural communities. This suggests that better screening mechanisms and indications must be determined to bring these mothers and fetuses to a center capable of advanced cardiac care.