Normal fetal circulation differs from that of the postnatal state. In the fetus, the pulmonary and systemic circulations are parallel, rather than occurring in series as in the normal circulation. In the fetal circulation, both ventricles eject blood into the aorta and receive systemic venous return. The right ventricle ejects a greater volume than the left ventricle. Postnatally, the circulation differs because the ventricles and the circulation are in series. The right ventricle receives the systemic venous return and ejects it into the pulmonary artery. The pulmonary venous return passes through the left atrium and the left ventricle alone ejects blood into the aorta. Left ventricular and right ventricular outputs are equal. The transition from a parallel to a series circulation normally occurs soon after birth; however, in a distressed neonate, the parallel circulation may persist, delaying the evolution to series circulation.

At birth, the distinctive features of fetal circulation and the vascular resistances are suddenly changed. A major reversal of resistance occurs because of the separation of the placenta and the onset of respiration. The loss of the placenta, which has acted essentially as an arteriovenous fistula, is associated with a doubling of systemic vascular resistance. The expansion of the lungs is associated with a sevenfold drop in pulmonary vascular resistance, principally from vasodilation of pulmonary arterioles secondary to an increase in inspired oxygen level to normal.

Coinciding with the fall in pulmonary vascular resistance, the volume of pulmonary blood flow increases and thus the volume of blood returning to the left atrium increases proportionately. The left atrial pressure rises, exceeds the right atrial pressure, and closes the foramen ovale functionally. In most infants for up to several months, a small left-to-right shunt occurs via the incompetent flap of the foramen ovale. Anatomically, the atrial septum ultimately seals in 75% of children and remains “probe-patent” in 25%.

The ductus narrows by muscular contraction within 24 hours of birth, although anatomic closure may take several days. The closure of the ductus is associated with a lowering of pulmonary arterial pressure to normal levels. When the ductus and foramen ovale close, the pulmonary blood flow equals systemic blood flow, and the circulations are in series.

In the neonatal period, the changes that occur in the ductus, foramen ovale, and pulmonary arterioles are reversible. The pulmonary arterioles and the ductus arteriosus are responsive to oxygen levels and acidosis. An increase in the vascular resistance occurs in conditions associated with hypoxia. Although minor changes occur at a PaO₂ of 50 mmHg, large increases in pulmonary vascular resistance occur at PaO₂ levels less than 25 mmHg. If acidosis coexists with hypoxia, the increase in pulmonary resistance is far greater than at comparable levels of PaO₂ occurring at normal pH.

Neonates with pulmonary parenchymal disease, such as respiratory distress syndrome, develop increased pulmonary vascular resistance and increased pulmonary arterial pressure because of hypoxia. If acidosis complicates the illness, the changes are even greater. This condition is often called persistent fetal circulation (PFC), or by the more physiologically descriptive term persistent pulmonary hypertension of the newborn (PPHN).

Because of the elevation of right ventricular systolic pressure, right atrial pressure increases, causing a right-to-left shunt at the foramen ovale. In a similar way, the ductus arteriosus of a neonate is also responsive to oxygen. With hypoxia, the ductus may reopen and, should the pulmonary resistance be simultaneously elevated, a right-to-left shunt could occur through the ductus arteriosus. Clinically, this is recognized by a lower PaO₂ (or pulse oximetry saturation) in the legs than arms.

Thus, cyanosis in the neonate with pulmonary parenchymal disease can result from right-to-left shunting of blood, as well as from intrapulmonary shunting and diffusion defects. Administration of 100% oxygen improves both of these abnormalities, but often the improvement is not great enough to exclude cyanotic cardiac malformations. Administration of oxygen to cyanotic patients with a cardiac anomaly generally also lessens the degree of cyanosis. With the development of echocardiography, the ability to distinguish these has been greatly enhanced.

Most cardiac malformations cause no problems in utero or in the immediate postnatal state. However, during the transition to the normal circulatory pattern, particularly as the ductus arteriosus is closing and then closes, certain malformations become evident. These malformations have one of three circulatory patterns in which the ductus played an important role during fetal life, and as it closes postnatally the neonatal circulatory pattern is disrupted.

The three types of malformations dependent upon ductal blood flow following birth are as follows: