In utero, blood flows in a parallel circuit with respect to the right and left ventricles. The highest oxygen content is in blood returning from the placenta via the umbilical vein. The ductus venosus is the first shunt encountered and connects the umbilical vein with the inferior vena cava, allowing roughly half of this oxygen-rich blood to be diverted away from the liver. Within the right atrium, a pressure gradient enables a significant portion of this oxygenated blood to be preferentially streamed across the foramen ovale to the left atrium. This allows the blood with the most oxygen content to be efficiently delivered, via the left ventricle and aorta, to the coronary and cerebral circulations. Right-ventricular outflow consists of a mixture of oxygenated blood from umbilical veins and desaturated blood from the superior and inferior vena cavi. Only 10% of right-ventricular blood actually passes into the pulmonary circuit because of high vascular resistance (the combined result of fluid-filled fetal lungs and medial-muscle hypertrophy in the small pulmonary arterioles). The remaining 90% of right-ventricular output is shunted away from the lungs through the ductus arteriosus and into the descending aorta, where it supplies the lower body or returns to the placenta.

The transition between fetal and neonatal circulation occurs primarily in response to changes in resistance throughout the circulatory system. The parallel circulation of the fetus is converted to a series system. Clamping of the umbilical cord eliminates the low-resistance placenta, and systemic vascular resistance increases. Without venous return from the placenta, right-atrial pressure decreases. As breathing is initiated, pulmonary vascular resistance falls dramatically, resulting in an increase in blood flow to the pulmonary circulation. In addition, higher pulmonary arterial oxygen tension (compared to the relatively hypoxemic fetal environment) contributes to lower pulmonary
vascular resistance. Due to remodeling of the pulmonary vasculature, a continued gradual reduction in pulmonary vascular resistance occurs during the first months of life. More blood flow to the lungs translates to greater pulmonary venous return to the left atrium. Elevated left pressure relative to the right atrium facilitates closure of the flap-like foramen ovale. Higher arterial oxygen concentration stimulates closure of the ductus arteriosus. Removal of the placenta also lowers circulating prostaglandin levels, which further facilitates ductal closure. The ductus arteriosus is functionally closed within the first 24 hours after birth; however, permanent closure requires thrombosis and fibrosis, which can take several months.