Recent Evidence on PDA Treatment in Premature Infants (2024-2026)

The Big Picture: A Shift Toward Conservative Management

Landmark Trials

1. The PDA Trial (JAMA, 2026) - PMID: 41364689

• Primary outcome (death or BPD): No significant difference - 80.9% (expectant) vs 79.6% (active treatment), p=0.73
• Survival: Expectant management had significantly higher survival - active treatment had more deaths (9.6% vs 4.1%, p=0.01), with more infection-related deaths in the treatment group
• Stopped early for futility and safety after interim analysis
• Bottom line: Active pharmacological treatment (acetaminophen, ibuprofen, or indomethacin) did not reduce death or BPD, but was associated with higher mortality

2. Baby-OSCAR Trial (NEJM, 2024) - PMID: 38265644

• Early ibuprofen did not reduce death or BPD (69.2% ibuprofen vs 63.5% placebo, p=0.10)
• Numerically more deaths in the ibuprofen group (13.6% vs 10.3%)
• Bottom line: Selective early ibuprofen for large PDA confers no benefit and may cause harm

Meta-Analyses

3. Active Treatment vs Expectant Management (JAMA Pediatrics, 2025) - PMID: 40423988

• Active treatment was associated with a significantly higher composite of death or BPD (RR 1.10, 95% CI 1.01-1.19, p=0.02)
• More deaths at 36 weeks in the active treatment group (14.3% vs 11.2%, RR 1.27, p=0.04)
• Trend toward more periventricular leukomalacia with active treatment (RR 1.50, p=0.06)

4. Heterogeneity in PDA Treatment Response (Eur J Pediatr, 2025) - PMID: 40240526

• Highlights that treatment response varies considerably by drug used, gestational age, and timing - underscoring the need for individualized approaches rather than blanket protocols

5. Fluid Restriction for PDA (Cochrane, Dec 2024) - PMID: 39692231

• Cochrane systematic review found insufficient evidence to recommend fluid restriction as a standalone strategy for symptomatic PDA closure

6. Early vs Late Treatment: Cochrane 2025 - PMID: 40548426

• Updated Cochrane review (June 2025) on early vs expectant management - found no clear benefit to early pharmacological intervention

Pharmacological Approaches

7. Prophylactic Acetaminophen (JAMA Pediatrics, 2026) - PMID: 41697673

• Prophylactic IV acetaminophen started within 12 hours of birth closed the ductus significantly more (71.2% vs 52.2% at day 7, RR 1.36)
• However, did not improve survival without morbidity (66.2% vs 63.6%, p=NS)
• Associated with higher cholestasis rate (6.4% vs 2.6%)
• Bottom line: Acetaminophen closes the PDA but does not translate to better clinical outcomes

Procedural / Transcatheter Closure

8. SCAI Position Statement (JSCAI, Aug 2025)

• Patient selection (respiratory status, echocardiographic findings, hemodynamic criteria)
• Device selection, imaging, anesthesia best practices
• Operator training benchmarks
• Institutional infrastructure requirements (targeted-neonatal echo/TnECHO, ventilation support)

Enteral Feeding During COX Inhibitor Treatment (Pediatr Int, 2026) - PMID: 41665023

Key Takeaways from 2024-2026 Literature

📚 SMART STUDY: Patent Ductus Arteriosus (PDA)

Pediatrics Resident / MRCPCH Level

PART 1: STRUCTURED NOTES

1. Anatomy & Embryology

• The ductus arteriosus is derived from the 6th aortic arch
• Connects the main/left pulmonary artery to the upper descending thoracic aorta, just distal to the left subclavian artery
• In the fetus: ductal flow = ~60% of combined ventricular output; direction is pulmonary artery → aorta (right to left)
• Length: 2-8 mm; diameter: 4-12 mm in infancy
• Normal closure → fibrosis → ligamentum arteriosum
• Failure of contraction of the muscular wall = primary cause of patency

2. Why Does It Stay Open?

3. Epidemiology

• Incidence: ~1 in 2,000 full-term births
• Female predominance: 2:1 (F:M)
• In preterm infants: ~75% at 28-30 weeks gestation
• Virtually all preterms ≤28 weeks with birth weight <1,750 g have PDA in first 24 hours
• Risk increases with decreasing gestational age and birth weight

4. Haemodynamics

• As pulmonary vascular resistance (PVR) falls (8-10 weeks postnatally), L→R shunt increases
• Results in: Left ventricular volume overload, ↑ left atrial pressure, ↑ pulmonary artery pressure, RV strain

• Blood flows from aorta into PA during diastole → low aortic diastolic pressure → bounding pulses and wide pulse pressure
• In preterm: "ductal steal" from gut, brain, kidneys → risk of NEC, IVH, renal failure

• Irreversible pulmonary vascular disease → PVR rises to systemic level
• Shunt reverses: PA → Aorta (right to left)
• Differential cyanosis: lower limbs blue (desaturated PA blood enters descending aorta), upper limbs pink
• Develops in ~5% of isolated PDA if untreated

5. Clinical Features

Auscultation

• Continuous "machinery" murmur - heard throughout systole AND diastole
• Best heard: left infraclavicular region / 1st-2nd left ICS below left clavicle
• As pulmonary pressure rises: diastolic component shortens, then murmur disappears in Eisenmenger
• Must distinguish from venous hum (loudest in neck, obliterated by compression of jugular vein, changes with head position)

Examination findings

• Bounding pulses / wide pulse pressure
• Hyperactive precordium
• Signs of heart failure in large PDAs: tachycardia, tachypnoea, poor feeding, failure to thrive
• No cyanosis in uncomplicated L→R PDA; cyanosis (especially differential) = late/reversed shunt

6. Investigations

7. Management

A. Conservative / Expectant (2024-2026 evidence now strongly supports this in preterm)

• Fluid restriction (evidence weak - Cochrane 2024 found insufficient data)
• Respiratory support optimisation
• 2026 JAMA PDA Trial: expectant management had lower mortality than active treatment in extremely preterm infants (4.1% vs 9.6% deaths, p=0.01)

B. Pharmacological (COX Inhibitors / Paracetamol)

Key 2024-2026 message: Pharmacological closure closes the ductus but does NOT improve death or BPD rates. Active treatment is associated with higher mortality than watchful waiting.

C. Surgical Ligation

• Posterior lateral thoracotomy (3rd/4th ICS)
• Ligation with clip or suture (neonates); division + oversewing (large/wide ductus)
• Caution: recurrent laryngeal nerve courses around the ductus - at risk for injury
• Reserved for: failed pharmacotherapy, contraindications to drugs, urgent closure

D. Transcatheter Occlusion (tcPDA)

• Devices: Rashkind double-umbrella, Gianturco coils, Amplatzer duct occluder
• Now preferred over surgery for most cases in older infants/children
• SCAI 2025 position statement: guidance for tcPDA in premature infants - patient selection (respiratory status, echo, haemodynamics), device selection, operator benchmarks
• Complications: thromboembolism, endocarditis, incomplete occlusion, vascular injury
• Not feasible in very small premature infants (vessel access limitations)

When NOT to close:

• Eisenmenger syndrome (pulmonary hypertension with reversed shunt) - closure is harmful/contraindicated
• Where PDA is duct-dependent (e.g. duct-dependent pulmonary or systemic circulation in complex CHD) - these need PGE1 to keep it open

8. Complications of Untreated PDA

• Heart failure (leading cause of death - ~30% mortality untreated isolated PDA)
• Infective endarteritis (~0.45%/year after 2nd decade; more common with small PDA)
• Eisenmenger syndrome (5% of isolated PDAs)
• Pulmonary hypertension
• In preterms: NEC, IVH, periventricular leukomalacia, BPD, renal failure (from ductal steal)

9. Natural History by Size

PART 2: HIGH-YIELD FLASHCARDS (Q&A)

PART 3: PRACTICE MCQs (MRCPCH Style)

• A. Immediate surgical ligation
• B. IV indomethacin
• C. IV ibuprofen
• D. Expectant management with supportive care
• E. Prophylactic IV paracetamol

• A. Male predominance (2:1); autosomal dominant
• B. Female predominance (2:1); multifactorial
• C. Equal sex ratio; X-linked recessive
• D. Male predominance (3:1); autosomal recessive
• E. Female predominance (3:1); chromosomal

• A. 0.1%
• B. 0.45%
• C. 2%
• D. 5%
• E. 10%

• A. Spontaneous closure of PDA
• B. Tricuspid regurgitation with RV failure
• C. Eisenmenger physiology with reversed shunt
• D. Development of Fallot tetralogy
• E. Pulmonary embolism

• A. Prophylactic paracetamol improved survival without morbidity at 36 weeks PMA
• B. Prophylactic paracetamol closed the ductus in 71% vs 52% placebo at day 7
• C. Prophylactic paracetamol was associated with a lower rate of cholestasis
• D. Prophylactic paracetamol reduced BPD rates significantly
• E. The trial was stopped early due to benefit in the paracetamol group

PART 4: MIND MAP OUTLINE

PATENT DUCTUS ARTERIOSUS
│
├── EMBRYOLOGY
│   ├── 6th aortic arch derivative
│   ├── Connects PA → Aorta (fetal: R→L)
│   ├── Postnatal: L→R (when PVR falls)
│   └── Closes → ligamentum arteriosum
│
├── WHY IT STAYS OPEN
│   ├── PGE2/PGI2 (keep open)
│   ├── Hypoxia / prematurity
│   ├── Rubella, high altitude
│   └── Failed TGF-β induction
│
├── CLINICAL
│   ├── Machinery murmur (L infraclavicular)
│   ├── Bounding pulses / wide pulse pressure
│   ├── Hyperdynamic precordium
│   └── Differential cyanosis (late/Eisenmenger)
│
├── INVESTIGATIONS
│   ├── Echo + Doppler (gold standard)
│   ├── CXR: ↑ vascularity, cardiomegaly
│   ├── ECG: LVH, LAE
│   └── Catheter: only if PHT suspected
│
├── MANAGEMENT (2024-2026 evidence)
│   ├── Expectant → preferred; lower mortality
│   ├── COX inhibitors (indomethacin/ibuprofen)
│   │   └── Close ductus; do NOT improve BPD/death
│   ├── Paracetamol: closes ductus; no outcome benefit
│   ├── Surgery: ligation (watch RLN)
│   └── Transcatheter: Amplatzer/coils; SCAI 2025 guidance
│
└── COMPLICATIONS
    ├── CHF (leading cause of death)
    ├── Endarteritis (0.45%/yr)
    ├── Eisenmenger (5%)
    └── Preterm: NEC, IVH, BPD, renal failure

PART 5: HIGH-YIELD MNEMONICS

• Prostaglandins (PGE2, PGI2)
• Respiratory distress / prematurity
• Altitude (high altitude hypoxia)
• Maternal rubella

• Large pulse pressure (bounding)
• Enlarged LA and LV on echo
• Failure (heart failure in large shunts)
• Tachycardia / tachypnoea
• Systolic + diastolic = continuous murmur
• Infraclavicular location
• Diastolic steal (NEC, IVH, renal)
• Eisenmenger if untreated long-term

PART 6: LATEST EVIDENCE SUMMARY (2024-2026)

Exam take-home: The era of routine pharmacological PDA closure is over. Watchful waiting is now first-line in most haemodynamically significant PDAs in preterm infants, backed by Level 1 evidence (JAMA 2026).