What is persistent ductus arteriosus (PDA) in premature infants?

What is Persistent Ductus Arteriosus (PDA) in Premature Infants?

Patent ductus arteriosus (PDA) is a congenital cardiovascular condition in which the ductus arteriosus—a normal fetal blood vessel connecting the pulmonary artery to the descending aorta—fails to close after birth beyond the normal age of spontaneous closure. 1

Normal Fetal Physiology and Transition at Birth

• During fetal life, the ductus arteriosus is an essential structure that allows 85% of fetal circulation to bypass the lungs by shunting blood from the pulmonary artery directly to the aorta, maintained by suprasystemic pulmonary vascular resistance 2
• At birth, oxygen inhalation triggers a biochemical cascade that normally results in reduced pulmonary vascular resistance and ductus arteriosus closure 2
• In full-term newborns, the ductus arteriosus typically closes shortly after birth as part of the transition from fetal to neonatal circulation 2
• The ductus may remain open during the first 6 weeks of life without being considered pathological 2
• Normal closure is stimulated by rising oxygen tension, withdrawal of vasodilatory mediators (prostaglandins, nitric oxide, adenosine), and activation of vasoconstrictors (endothelin-1, catecholamines) 3

Epidemiology in Premature Infants

• The occurrence of PDA is inversely related to gestational age and weight, with closure delayed in up to 80% of infants born at 25 to 28 weeks of gestation 4, 5
• In term infants, PDA accounts for 5-10% of all congenital heart disease and occurs in approximately 0.3% to 0.8% of term infants 6, 5
• PDA is twice as common in females compared to males 6
• In preterm infants, PDA becomes symptomatic in approximately 40% of cases 7

Pathophysiology in Premature Infants

The fundamental problem in premature infants is that normal physiologic mechanisms contributing to ductal closure—oxygen tension and decreased prostaglandins—are altered due to immaturity 5

• In term infants, PDA is usually associated with a functional defect, whereas in preterm infants it is associated with immaturity 5
• As pulmonary vascular resistance decreases (especially in extremely low gestational age newborns), left-to-right shunting through the ductus increases, leading to pulmonary overcirculation 4, 3
• This persistent left-to-right shunt results in pulmonary overcirculation and systemic hypoperfusion 4
• Increased pulmonary blood flow leads to interstitial pulmonary edema and volume load to the left heart 3

Clinical Manifestations and Hemodynamic Consequences

The clinical manifestations depend on the size of the ductus and the relative systemic and pulmonary vascular resistances 6

Classification by Severity:

• Trivial/silent PDA: Hemodynamically insignificant; no murmur heard on auscultation 1
• Small/audible PDA: Likely hemodynamically insignificant; murmur heard on auscultation 1
• Moderate PDA: Likely hemodynamically significant 1

Clinical Signs:

• Continuous "machinery" murmur 8
• Tachycardia 5
• Bounding peripheral pulses 8, 5
• Wide pulse pressure 8
• Congestive heart failure and associated symptoms 5

A critical pitfall is that symptoms are not always present; therefore, diagnostic imaging is essential if PDA is suspected on clinical grounds 5

Associated Morbidities in Premature Infants

Potential consequences of hemodynamically significant PDA (hsPDA) include: 3

• Prolonged mechanical ventilation
• Bronchopulmonary dysplasia (chronic lung disease)
• Necrotizing enterocolitis or focal intestinal perforation
• Intraventricular hemorrhage
• Death

Long-term morbidities associated with PDA include chronic lung disease, retinopathy of prematurity, and neurodevelopmental delay 4

Diagnostic Approach

• Echocardiography with color Doppler is the key diagnostic technique 8
• Assessment must include degree of left ventricular volume overload, pulmonary artery pressure, pulmonary artery size, and right heart changes 8
• Continuous-wave Doppler ultrasonography can assess aortic reverse flow semi-quantitatively using the R/F ratio (retrograde to forward flow ratio) 7
• An increased R/F ratio indicates presence of symptomatic PDA in preterm infants 7
• Oxygen saturation should be measured in feet and both hands to assess for right-to-left shunting 6

Management Strategies

Three management strategies are currently available for PDA: conservative/medical management, pharmacologic intervention, and surgical ligation 5

Conservative/Medical Management:

• Mild fluid restriction 5
• Increased airway pressures 5
• Supportive care 5

Pharmacologic Treatment:

• Accomplished using indomethacin, ibuprofen, or acetaminophen (paracetamol) 4, 5
• While both indomethacin and ibuprofen lysine show similar efficacy, ibuprofen lysine demonstrates an improved safety profile, particularly regarding renal effects 5

Surgical Intervention:

• Direct surgical closure or percutaneous ligation 4

Treatment Timing Approaches:

There is a subgroup of infants who will likely benefit from intervention: 3

1. Prophylactic intravenous indomethacin in highly selected extremely low gestational age newborns with PDA (<26 weeks' gestation, <750 g birth weight)
2. Early targeted therapy in selected preterm infants at particularly high risk for PDA-associated complications
3. PDA ligation, catheter intervention, or oral paracetamol as rescue options for hsPDA closure

Important Clinical Pitfalls

• Do not assume stability based solely on clinical examination—always confirm with echocardiography, as serious complications like pulmonary vascular disease can develop 2
• Do not overlook differential cyanosis—always check oxygen saturation in all four limbs to detect right-to-left shunting at the ductal level 2
• In the last decade, there has been a trend toward less aggressive treatment of PDA in preterm infants, recognizing that not all PDAs require intervention 3
• Absence of a universal scoring system for severity of PDA limits accuracy of comparisons among research studies 4