• Associated with Char syndrome (autosomal dominant; TFAP2B gene mutation → facial dysmorphism, PDA, hand anomalies) ^[3][4]
• Associated with chromosomal abnormalities: trisomy 21, trisomy 18, 22q11 deletion
• Higher incidence in other genetic syndromes (e.g., Holt-Oram, Noonan)

• Maternal rubella (especially first trimester infection — rubella embryopathy classically causes PDA + peripheral pulmonary artery stenosis) ^[3][4]
• Prematurity — the single most important risk factor ^[3][4]
• Birth at high altitude (chronic hypoxia prevents the normal postnatal oxygen-mediated ductal constriction) ^[3][4]
• Low birth weight
• Perinatal asphyxia (relative hypoxia delays closure)
• Excess fluid administration in neonates

• The ductus arteriosus derives from the embryonic left 6th aortic arch ^[2]
• Aortic end: arises distal to the left subclavian artery ^[2][3]
• Pulmonary end: inserts at the junction of the main and left pulmonary arteries ^[2][3]
• The DA is a muscular artery (unlike the elastic aorta) — this is critical because its closure depends on smooth muscle contraction

In utero, the lungs are collapsed and filled with fluid → pulmonary vascular resistance (PVR) is very high. Only ~10% of right ventricular output goes to the lungs. The remaining ~60% of total cardiac output from the RV is diverted through the DA into the descending aorta to supply the systemic circulation (especially the lower body and placenta) ^[3][4].

This means in fetal life, the shunt is right-to-left (pulmonary artery → aorta), which is the physiological direction.

At birth, two key changes trigger ductal constriction ^[3][4]:

1. ↑PaO₂ (first breath → lungs expand → oxygen enters): Oxygen inhibits the voltage-gated K⁺ channels in ductal smooth muscle → membrane depolarisation → Ca²⁺ influx → smooth muscle contraction. The ductal smooth muscle is uniquely oxygen-sensitive (unlike systemic arteries).

2. ↓Circulating PGE₂: Removal of the placenta (the major source of PGE₂) + increased pulmonary metabolism of PGE₂ by the now-functioning lungs → loss of the vasodilatory stimulus.

Timeline of closure:

• Functional closure: 10–15 hours after birth (smooth muscle constriction) ^[3][4]
• Anatomical closure: 2–3 weeks (intimal proliferation, fibrosis → becomes the ligamentum arteriosum) ^[3][4]

In preterm infants, the ductal smooth muscle is immature and has fewer oxygen-sensitive K⁺ channels + higher sensitivity to PGE₂ → this is why PDA is so common in preterms and why COX inhibitors (indomethacin/ibuprofen) work to close it (they reduce PGE₂ synthesis).

In term infants with PDA, the cause is usually:

• Structural abnormality of the ductal wall (deficient smooth muscle, abnormal elastic tissue)
• Genetic predisposition (TFAP2B mutations in Char syndrome)
• Environmental damage (rubella virus destroys ductal wall elastin)

In preterm infants, the cause is:

• Immature ductal smooth muscle with fewer oxygen-sensitive K⁺ channels
• Higher circulating PGE₂ levels
• Increased sensitivity to PGE₂
• Lower ability to generate endothelin-1 (a constrictor)

In PDA, the patent DA acts as a left-to-right shunt ^[3][4]:

Why left-to-right? After birth, systemic vascular resistance (SVR) is much higher than pulmonary vascular resistance (PVR). Since the DA connects the high-pressure aorta to the lower-pressure pulmonary artery, blood flows aorta → pulmonary artery (left-to-right).

Shunting occurs in PDA since the resistance and pressure in the pulmonary arterial bed < systemic arterial bed ^[2].

The cascade of events ^[3][4]:

PDA present
  → L-to-R shunt (aorta → pulmonary artery)
    → ↑Pulmonary blood flow (pulmonary overcirculation)
      → ↑Pulmonary venous return to left atrium
        → ***LV volume overload*** [1][2]
          → LV dilatation → ↑stroke volume (Frank-Starling) → hyperdynamic circulation
            → ↑Pulse pressure (wide pulse pressure), bounding pulses
              → If large shunt persists: LV failure (HF)

By 6–8 weeks, ↓PVR leads to ↑shunting → ↑pulmonary venous return → LV volume overload + hyperdynamic circulation ^[3][4].

Unlike VSD (where the shunt is mainly systolic because the ventricles only generate pressure during systole), the PDA connects two great arteries. The aortic pressure exceeds pulmonary artery pressure in both systole AND diastole → flow through the PDA is continuous → this explains the characteristic continuous "machinery" murmur ^[4].

May lead to Eisenmenger syndrome after pulmonary arteriole remodelling with differential cyanosis ^[3][4].

If a large PDA is left untreated → chronic pulmonary overcirculation → pulmonary vascular remodelling (intimal hyperplasia, medial hypertrophy, fibrosis of pulmonary arterioles) → irreversible pulmonary hypertension → PVR eventually exceeds SVR → shunt reversal to right-to-left (deoxygenated blood from PA → aorta distal to left subclavian).

This causes differential cyanosis — a phenomenon unique to PDA-related Eisenmenger:

• Upper body (right hand, head): Normal saturation (supplied by aorta proximal to DA insertion, i.e., pre-ductal)
• Lower body (feet, left hand sometimes): Cyanosed (supplied by aorta distal to DA insertion, receiving deoxygenated blood from PA)

Differential cyanosis + differential clubbing = pathognomonic of Eisenmenger syndrome from PDA ^[3][4]. The feet are cyanosed and clubbed while the right hand is pink and normal.

This is the most clinically useful classification, based on Qp:Qs ratio (pulmonary-to-systemic blood flow ratio) ^[4]:

This classification is mainly relevant for interventional catheter closure device selection.

PDA in preterms deserves special mention because it is extremely common and presents differently:

There is no universally agreed single definition, but the following echo and clinical parameters are used in combination:

Clinical signs of haemodynamic significance (complement echo findings):

• Widened pulse pressure (systolic − diastolic > 25 mmHg)
• Bounding pulses, hyperdynamic precordium
• Worsening ventilatory requirements
• Metabolic acidosis
• Oliguria, feed intolerance

CXR is the first-line imaging and gives a quick overview of heart size and pulmonary vascularity.

How to read pulmonary vascularity on paediatric CXR:

• Pulmonary plethora = pulmonary arteries visible in the outer third of lung fields; vessels appear enlarged and numerous → suggests L-to-R shunt with ↑ pulmonary blood flow
• Oligaemic lung fields = paucity of pulmonary vessels → suggests ↓ pulmonary blood flow (e.g., TOF, pulmonary atresia)
• Pulmonary venous congestion = cephalisation (upper lobe vessel prominence), Kerley B lines, interstitial/alveolar oedema → suggests LV failure or obstructed pulmonary venous return

In PDA, you expect plethora (↑ flow), not congestion (↑ pressure from LV failure) — unless the patient is in frank LV failure, in which case both may coexist.

ECG reflects the haemodynamic burden on cardiac chambers. It does not diagnose PDA directly but gives information about volume/pressure overload patterns.

Age-specific ECG interpretation in paediatrics — a critical point:

• Neonates normally have right-axis deviation and RV dominance (because in utero the RV is the dominant ventricle pumping against high PVR)
• Over the first 6 months, the axis gradually shifts leftward as LV becomes dominant
• Therefore, persistent RVH beyond 6 months or progressive RVH in a child with known PDA = developing pulmonary hypertension — a red flag

Echo is diagnostic and allows estimation of size ^[4]. It is the single most important investigation in PDA. Transthoracic echocardiography (TTE) is used in essentially all paediatric cases (transoesophageal echo is rarely needed).

What Echo Assesses:

Echo is the gold standard for PDA diagnosis, sizing, and haemodynamic assessment in all age groups ^[2][4].

Pulse oximetry screening is now widely used for critical congenital heart disease (CCHD) in neonates. While PDA per se is not the target of pulse oximetry screening (the screen targets duct-dependent cyanotic lesions), oximetry is useful in PDA assessment:

In a neonate, a pre-post ductal SpO₂ difference > 3% is significant and warrants urgent echocardiography.

Cardiac catheterisation is not routinely needed for diagnosis of PDA in the current era (echo is sufficient). However, it is used in specific circumstances:

Key catheterisation findings in PDA:

Rarely needed in isolated PDA but may be used in:

• Complex anatomy where echo windows are suboptimal
• Adolescent/adult PDA with calcification (CT better delineates calcified duct)
• Assessment of associated aortic arch anomalies
• Delineation of major aortopulmonary collateral arteries (MAPCAs) in pulmonary atresia with VSD ^[3]

Not diagnostic for PDA but important in overall assessment:

• Echo is performed early (often day 2–3) in very preterm infants (< 28 weeks) because of the high incidence of hsPDA
• Clinical signs may be subtle initially — widened pulse pressure, hyperdynamic precordium, and worsening ventilatory requirements are often the first clues
• BNP/NT-proBNP can be used as an adjunct to guide whether to treat: markedly elevated levels correlate with hsPDA
• Cranial ultrasound should be done concurrently to screen for IVH (a complication of PDA-related fluctuating cerebral blood flow)
• The murmur may be confined to systole in the neonatal period before ↓PVR ^[4] — do not wait for a "classic continuous murmur" before investigating a preterm with suspected PDA

• CXR + ECG + Echo is the standard workup
• CXR: cardiomegaly with pulmonary plethora; ECG: LVH + LAE ^[4]
• Echo confirms PDA, quantifies shunt, and — critically — excludes coexisting coarctation of aorta and other anomalies

• Often detected during school health screening or sports pre-participation evaluation
• CXR and ECG may be normal ^[4] if the PDA is small
• Echo confirms the diagnosis even in an asymptomatic child with a continuous murmur

• If the presentation is a cyanotic neonate or a neonate in shock after duct closure → urgent echo to define the underlying anatomy
• PGE₁ infusion must be started empirically while awaiting echo if duct-dependent circulation is suspected ^[2][8]
• PGE₁/PGE₂ side effects: fever, hypotension, bradycardia, apnoea, seizure-like activities ^[2][8] — the baby must be monitored in a high-dependency or intensive care setting

Ductal-dependent congenital heart diseases depend upon a patent ductus arteriosus to supply the pulmonary or systemic blood flow or to allow adequate mixing between parallel circulations ^[2][8].

Continuous infusion of PGE₁/PGE₂ is useful for initial stabilisation of infants with a duct-dependent circulation prior to surgical interventions ^[2][8].

Side effects of PGE₁ = Fever, Hypotension, Bradycardia, Apnoea, Seizure-like activities ^[2][8].

Mnemonic for PGE₁ side effects: "Feverish Hypotensive Baby Apnoeic Seizing"

For all preterm PDAs (including haemodynamically significant ones), initial conservative measures should be optimised:

Many preterm PDAs (especially in infants > 28 weeks) will close spontaneously with conservative management alone. The trend in current neonatology is towards patience.

If pharmacological closure fails or is contraindicated, proceed to:

Indications for surgical/interventional closure ^[2][8]:

The Controversy: Should Small, Asymptomatic PDAs Be Closed?

Closure of small ducts for the sole purpose of eliminating the risk of IE is recommended by most authorities but has been challenged ^[2].

• Arguments for closure: Lifetime risk of infective endarteritis (estimated ~0.45% per year); the procedure is low-risk; "why leave a lesion that serves no purpose?"
• Arguments against: Very low IE risk; procedure carries small but non-zero risk; some "silent" tiny PDAs may be physiologically insignificant
• Current (2025–2026) consensus: Most paediatric cardiologists recommend closure of all PDAs detectable on echocardiography (except truly "silent" PDAs detectable only by very sensitive Doppler). The AHA/ACC guidelines recommend closure of small PDAs with audible murmur. Truly silent PDAs (no murmur, incidental echo finding) are observed.

Furosemide + Digoxin ^[2]:

• Indicated in term infants < 5 kg who have symptomatic PDA until they are large enough to safely undergo percutaneous PDA occlusion ^[2]

Closure is CONTRAINDICATED in Eisenmenger syndrome ^[3]:

Heart failure is the most common complication of a moderate-to-large PDA and is the primary indication for closure.

This is the most feared long-term complication of an unrepaired large PDA.

Eisenmenger syndrome: triad of (1) congenital L-to-R shunt (2) pulmonary arterial disease (3) cyanosis ^[4].

Incidence: up to 80% in large VSD and PDA in infancy/early childhood if untreated ^[4].

Why does Eisenmenger develop faster in PDA than ASD?

• PDA exposes pulmonary arterioles to both high-pressure and high-flow shunting (aortic pressure is transmitted directly to the PA)
• ASD involves only low-pressure, high-flow shunting (RA → LA gradient is small)
• Therefore PDA and VSD cause Eisenmenger much sooner (years) than ASD (decades)

Complications of Eisenmenger Syndrome Itself [3][4]

Once Eisenmenger develops, the patient faces a cascade of secondary complications:

Prognosis of Eisenmenger: 30–40% 10-year mortality with mean age of death at 37 years if transplant not done ^[3][4].

This is one of the main justifications for closure of even small PDAs — to eliminate the lifetime risk of endarteritis.

Preterm infants face unique complications due to the diastolic steal phenomenon — blood that should perfuse end-organs during diastole instead runs through the PDA back into the pulmonary artery: