Radiological Markers for PDA Management in Preterm Infants

Novel Radiological Markers for PDA-Targeted Management in Preterm Infants: A Randomized Controlled Trial

The aim of this Randomized controlled trial is to determine whether Echo with Organ Doppler-guided management strategy for hemodynamically significant patent ductus arteriosus (hsPDA) improves the short-term outcomes compared with standard care in preterm neonates.

the research question is Does the usage of new radiological markers minimize the hsPDA group and decrease the pharmacological management in order to decrease the side effects of the treatment ? Researchers will compare the Echo with Organ Doppler management group to the standard care group.

1. All neonates enrolled in the study will be subjected for:

   Demographic data

   • Gestational age at birth, birth weight (grams), sex, mode of delivery, Ballard score, Apgar score and anthropometric measurement.

   Maternal data • Including antenatal corticosteroid exposure, history of chorioamnionitis and premature rupture of membranes.

   Medical History

   • Including respiratory distress syndrome, oxygen requirement and total duration of mechanical ventilation in days.

   Clinical Examination

   • Each neonate will undergo a detailed clinical examination including assessment of vital signs (heart rate, respiratory rate, temperature, and mean arterial pressure appropriate for gestational age), Respiratory examination and oxygen requirement, cardiac, abdominal and neurological examinations.

   Investigations Laboratory: CBC, CRP and Arterial blood gas parameters (ABG), renal function test.

   Imaging: Trans cranial US, abdominal US

   Group Allocation and Management

   GROUP 1: INTERVENTION (Echo and Doppler-Guided) Initial Assessment (24-72 hours)

   All infants in the intervention group undergo:

1. Comprehensive Echocardiography

   Timing of Assessments • T0: 24-72 hours of life (baseline). • T1: Prior to PDA treatment (if hsPDA diagnosed in Intervention group). • T2: 24-48 hours after treatment.

   • All scans are performed by the principal investigator (neonatologist) using a standardized protocol. Images and Doppler traces are stored for quality control.

   ECHO parameters:

   Include a statement on hemodynamic significance based on 5 parameters: (Winners et al. (2023).

1. Diameter 2. Flow direction 3. Systolic and diastolic flow velocities 4. Indices of pulmonary over circulation 5. Left ventricular output

• Plus, one parameter of left sided volume loading or left heart pressure loading, systemic shunt effect, doppler flow patterns in the systemic circulation.

  2. Organ Doppler (Superior mesenteric artery (SMA) and Middle cerebral artery (MCA)).

• Two arteries, one primary parameter: End-diastolic velocity (EDV). *Definition of abnormal organ Doppler: Any abnormality in SMA or MCA (low EDV or ARDF) (Mifflin et al., 2026).

Step 2: Treatment Decision PDA classification is based on echocardiographic and Doppler findings. An echo-significant and Doppler-significant PDA is classified as a hemodynamically significant PDA (hsPDA), representing a true-positive diagnosis, and is treated pharmacologically. An echo-significant but Doppler-normal PDA is classified as a borderline hsPDA and requires supportive care only. When the echocardiographic findings are non-significant, the PDA is classified as a non-significant PDA, and no treatment is required.

Rationale: Treatment is reserved for infants with BOTH echo evidence of hemodynamic significance AND organ Doppler evidence of systemic hypoperfusion (steal phenomenon).

GROUP 2: CONTROL (Standard Clinical + Echo-Guided)

Step 1: Initial assessment (24-72 hours) and classification based on clinical criteria and Echo (without doppler):

• Clinical criteria:

  • Oxygen requirement >30% OR
  • Respiratory support (CPAP/ventilator) OR
  • Wide pulse pressure (>25 mmHg) OR
  • Bounding pulses.

• Echo criteria:

Include a statement on hemodynamic significance based on 5 parameters: (Winners et al. (2023).

1. Diameter

2. Flow direction

3. Systolic and diastolic flow velocities

4. Indices of pulmonary over circulation

5. Left ventricular output.

   Step 2: Treatment Decision Patients with both clinical signs and echocardiographic evidence of a significant PDA were classified as hsPDA and received pharmacological treatment. In contrast, patients with no clinical signs and/or non-significant echocardiographic findings were classified as non-significant PDA and received supportive care only. This approach was based on traditional clinical and echocardiographic criteria without organ Doppler assessment.

   Pharmacologic Treatment Protocol

   Indications for Treatment:

   • Intervention Group: Echo-significant and Doppler-significant

   • Control Group: Clinical signs and Echo-significant Pharmacological treatment: I.V Paracetamol
   • Dose: 15-20 mg/kg loading, then 7.5 mg/kg every 6 hours for 3-6 days.

   Outcome Measurements Primary Outcome

   Composite of survival without major morbidity until 36 weeks PMA or discharge:

   - No BPD (oxygen/respiratory support at 36 weeks PMA).

   - No NEC ≥ Bell stage II.

   - No IVH ≥ grade II (Papile classification).

   - No death.

   Secondary Outcomes

   Clinical:

   - Duration of invasive ventilation.

   - Days on supplemental oxygen.

   - Incidence of BPD, NEC ≥ stage II, IVH ≥ grade II, PVL.

   - Need for PDA closure (medical second course, transcatheter, or surgical).

   • NICU length of stay.
   • In-hospital mortality.

   Hemodynamic / Doppler (Intervention group only):

   • Change in SMA EDV from T0, 1 to T2 and T3.
   • Change in MCA EDV from T0, 1 to T2 and T3.
   • Proportion of infants with improvement in organ Doppler after treatment.
   • Association between Doppler parameters and major morbidities.

   Safety:

   - Renal dysfunction after treatment (rise in creatinine, oliguria).

   • Gastrointestinal bleeding or suspected NEC post-treatment.
   • Thrombocytopenia or other drug-related adverse events.

Inclusion Criteria:

• Gestational age <34 weeks and/or birth weight <1800 g.
• Admitted to the NICU at Assiut University Children Hospital within the first 24 hours of life.
• First echocardiographic assessment performed between 24 and 72 hours of life.

Exclusion Criteria:

• Major congenital heart disease other than PDA (e.g., coarctation, critical left heart lesions).
• Life-limiting congenital anomalies or chromosomal disorders.
• Severe septic shock or multiorgan failure at time of first assessment.
• Death or transfer before completion of initial Echo and Doppler (<24 hours of life).