The differential diagnosis of the neonate presenting with nonspecific symptoms such as tachypnea, lethargy, poor feeding, poor perfusion, or hypothermia is broad. Neonatal sepsis is frequently considered as one of the top diagnoses in such cases, but it must also be remembered that certain forms of congenital heart disease (CHD) can present in a similar fashion. The absence of a fever in a newborn that otherwise has the presentation of sepsis should especially raise the suspicion for a ductal-dependent congenital cardiac lesion.

The ductal-dependent forms of CHD are those that depend on a patent ductus arteriosus to supply adequate systemic or pulmonary blood flow. These lesions can be confused with neonatal sepsis because the timing of onset of symptoms correlates with the natural history of ductal closure at several hours to several days of life. The neonates may initially appear well and have no significant clinical findings until the ductus closes. The onset of symptoms can then be abrupt and life-threatening, as flow to the systemic or pulmonary bed becomes limited. One category of ductal-dependent CHD is that of left-sided outflow obstruction, including severe aortic stenosis, coarctation of the aorta, interrupted aortic arch, and hypoplastic left heart syndrome. In all of these cases, the systemic blood flow is initially maintained by the presence of a patent ductus arteriosus, and the neonate continues to have a fetal circulation with the right ventricle providing systemic blood flow. The neonate with left-sided outflow obstruction is unable to transition to the normal postnatal left-dominant circulation when the ductus closes. The left-sided outflow obstruction results in decreased cardiac output with diminished systemic perfusion. The ultimate clinical picture is that of metabolic acidosis and shock associated with the nonspecific symptoms mentioned above. Likewise, patients with a right-sided ductal dependent
lesion are those that rely on the patent ductus to maintain pulmonary perfusion. These lesions include severe pulmonary stenosis, tetralogy of Fallot, and various forms of pulmonary atresia. In these cases, transition to postnatal circulation creates a dramatic decrease in pulmonary blood flow, resulting in a similar septiclike picture along with significant cyanosis.