Patent ductus arteriosus


The ductus arteriosus is a fetal structure that communicates between the descending thoracic aorta and the pulmonary artery.

The ductus arteriosus allows most of the blood from the right ventricle to bypass the fetus’s fluid-filled non-functioning lungs.

It closes at birth, and becomes the ligamentum arteriosum.

At term birth, separation from the placenta and expansion of the lungs, leads to reduce pulmonary artery pressure and increased oxygen saturation, which are key contributors to closures of the duct.

in premature infants, birth is not sufficient to close the duct, leading to a patent ductus arteriosus, which is the most common cardiac condition in newborn infants.

The probability of PDA is inversely proportional to the gestational age of birth.

Infants born at extreme prematurity of less than 28 weeks gestation are at most risk for PDA.

A prolonged  patency of the ductus arteriosus results in left to right shunting and increases the risk of complications including: bronchopulmonary dysplasia, pulmonary hemorrhage, intraventricular hemorrhage, necrotizing enterocolitis, and death.

The ductus arteriosus is formed from the left 6th aortic arch during embryonic development.

It attaches to the final part of the aortic arch and the first part of the pulmonary artery.

Occurrence rate 6 times as many cases in babies born at high altitude than at sea level reflecting the importance of oxygen.

Closure of DA completed in normal term infants within 72 hours of birth.

When the ductus arteriosus does not close normally, it is associated with increased neonatal mortality and morbidity, including bronchopulmonary dysplasia, necrotizing enterocolitis, and intraventricular hemorrhage.

At birth, pulmonary blood flow increases 8- to 10-fold and pulmonary arterial pressure decreases by 50% within 24 hours.

In utero it functions to divert placental blood away from the fetal pulmonary bed into the fetal systemic circulation with high nutrient and oxygenated blood.

Failure to close in extremely premature is referred to as patent ductus arteriosus.

Patent ductus arteriosus results in the abnormal flow of blood from the aorta to the pulmonary artery resulting in a left-to-right shunt.

Represents up to 10% of cases of congenital cardiac disease.

Common in preterm infants

Frequency of .02-.04% among full term infants and as high as 60% among infants delivered before 28 weeks of gestation.

Following birth the communication usually undergoes constriction and obliteration.

Consequences are a right to left shunt with high pulmonary blood flow and low systemic output.

Prostaglandins are responsible for maintaining the opening of the ductus arteriosus.

Prostaglandins dilate vascular smooth muscle throughout the fetal period.

Prostaglandin E2 is produced by both the placenta and the ductus arteriosus.

Prostaglandin E2 is the most potent of the E prostaglandins.

Prostaglandin E1 (PGE1) also has a role in keeping the ductus arteriosus open.

PGE1 and PGE2 keep the ductus arteriosus open by involvement of the specific PGE-sensitive receptors: EP4 and EP2.

The major PGE receptor is EP4 that is associated with PGE2-induced dilation of the DA and can be found across the DA in smooth muscle cells.

Following birth the levels of both PGE2 and the EP4 receptors are reduced significantly, allowing for closure of the DA and establishment of normal postnatal circulation.

Ductus arteriosus closure may be induced by administration of nonsteroidal anti-inflammatory drugs (NSAIDs), as they inhibit prostaglandin production.

Indomethacin is the most common NSAID used.

It is usually administered in the first week after birth.

In the presence of a congenital defect with impaired lung perfusion oxygenation is improved by maintaining the ductus open with prostaglandin treatment.

With an abnormal ductus prostaglandin treatment is ineffective.

Persistence of the ductus is much more common in females.

By inhibiting PGE2 formation, EP4 receptor activation will decrease and normal circulation begins.

NSAIDs administered late in pregnancy can cross the placenta and lead to premature closure of the DA in the fetus.

In such cases exogenous PDE2 can be administered to reverse the effects of the NSAIDs and maintain the patency of the DA for the remainder of the pregnancy.

A patent ductus arteriosus occurs in approximately 4% of infants with Down syndrome.

Failure to thrive is a very common sign of patent ductus arteriosus.

Hemodynamic consequences of PDA are left to right shunt with high pulmonary bloodflow and low systemic output.

If left uncorrected, this usually leads to pulmonary hypertension followed by right ventricular heart failure, as well as possible cardiac arrhythmias.

Symptoms include shortness of breath, exercise intolerance, edema, and palpitations.

25-40% of individuals are asymptomatic.

Impaired respiration related to transudation of pulmonary fluid and pulmonary interstitial juxtacapillary receptor stretching due to increased pulmonary arterial blood flow and elevated pulmonary venous pressures.

Patent ductus  arteriosuspersistent beyond three days is  associated with higher mortality and morbidity, and a higher risk of bronchopulmonary dysplasia in among infants without PDA.

Complication includes development of severe pulmonary hypertension with right-to-left shunting and cyanosis, the Eisenmenger’s syndrome.

In extremely preterm infants, a large patent ductus arteriosus present in three days is associated with high mortality and morbidity and a high risk of bronchopulmonary dysplasia.

May lead to pulmonary hemorrhage, hypotension, intra ventricular hemorrhage, necrotizing enterocolitis and death.

Can present as congestive heart failure in adults.

Transthoracic echocardiography 100% specificity and 42% sensitivity for diagnosis.

Best echocardiographic views are the suprasternal notch view and high para sternal short-axis view of the heart at the level of the pulmonary artery bifurcation.

Magnetic resonance angiography, and multislice CT of the chest can also identify this abnormality.

At cardiac catheterization arch angiography or direct ductal injection can be performed.

Natural history depends on the size of the ductus, shunt and whether pulmonary vascular obstruction disease and pulmonary hypertension develop.

95% of infants at birth with a patent ductus arteriosus have a left to right shunt with normal or near normal pulmonary pressures.

Optimal treatment unknown as trials of treatment have not demonstrated benefits on survival or long-term outcome.

Metaanalysis of randomized controlled trials showed that pharmacological treatment with cyclooxygenase inhibitors induced PDA closure, but had no beneficial effect on clinical outcomes.

Cyclooxygenase inhibitors may reduce the need for surgical PDA  closure in symptomatic infants, but prophylactic use of these drugs does not provide a benefit for outcome of death, or moderate to severe neurodevelopmental disabilities.

Cyclooxygenase inhibitors carry risk of adverse side effects that include bleeding and renal injury.

Acetaminophen is a noninferior alternative to ibuprofen and indomethacin.

Numerous randomized studies failed to demonstrate any benefit of treatment and survival and long-term outcome.

The use of a trans catheter Amplatzer Occluder has a favorable safety profile.

Screening extremely preterm infants with echocardiogram for PDA before day three of life is associated with lower in-hospital mortality and pulmonary hemorrhage but not with differences in necrotizing enterocolitis, severe bronchopulmonary dysplasia with severe cerebral lesions (Roze JC et al).

The incidence of PDA is inversely proportional to gestational age, with more than 40% of infants, born at less than 28 weeks gestation have PDA persist by four months of age.

The risk of bronchopulmonary, dysplasia, or death in extremely preterm infants, increases with the persistence of PDA beyond 1-2 weeks.

Cyclooygenase inhibitors can induce ductal constriction.

Expected management for PDA extremely premature infants was not inferior to early ibuprofen treatment with respect to necrotizing enterocolitis, bronchopulmonary, dysplasia, or death at 36 weeks post menstrual age.

Treatment with indomethacin reduces rate of pulmonary hemorrhage (Kluckow M et al).

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