Ibuprofen vs Expectant Management for hsPDA in Preterm Infants: Retrospective Cohort (IMPACT-PDA)

Individualized Management Over Routine Intervention: Evidence Against Early Ibuprofen for PDA From Combined Retrospective and Meta-Analytic Data

This retrospective cohort study compares ibuprofen treatment versus expectant management for hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants. Data were collected from preterm infants with hsPDA admitted to the Department of Neonatology, Shengjing Hospital of China Medical University between June 2020 and June 2025. A total of 541 infants were included: 241 received ibuprofen and 300 received expectant management (no routine pharmacological closure, supportive care only). The primary outcome is PDA closure rate. Secondary outcomes include bronchopulmonary dysplasia (BPD), mortality, pulmonary hypertension, renal insufficiency, neonatal pneumonia, retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH), pulmonary hemorrhage, and gastrointestinal bleeding. Analyses are stratified by gestational age (<28 weeks, 28-33 weeks, 33-37 weeks) and adjusted for sex, multiple gestation, and maternal factors. The study aims to provide real-world evidence on the risks and benefits of ibuprofen closure in different gestational age subgroups.

Study Overview

• Status: Completed
• Conditions: Patent Ductus Arteriosus; Infant, Premature
• Intervention / Treatment: Drug: Ibuprofen

Detailed Description

Background: Patent ductus arteriosus (PDA) is common in preterm infants. When hemodynamically significant (hsPDA), it may lead to pulmonary overcirculation, systemic hypoperfusion, and increased risk of bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), and other neonatal morbidities. Pharmacological closure with cyclooxygenase inhibitors such as ibuprofen is often used, but the benefits of routine closure remain controversial, particularly across different gestational age groups. Expectant management (allowing spontaneous closure without drugs) has gained interest, but comparative data are limited.

Objectives:

To compare ibuprofen versus expectant management for PDA closure and neonatal outcomes in preterm infants with hsPDA.

To examine effect modification by gestational age (<28 weeks, 28-33 weeks, 33-37 weeks).

To explore associations with sex, multiple gestation, and maternal factors. Study design: Single-center retrospective cohort study.

Setting: Department of Neonatology, Shengjing Hospital of China Medical University, Shenyang, China.

Participants: Preterm infants with echocardiographically confirmed hsPDA born between June 2020 and June 2025. Exclusion criteria: major congenital anomalies, chromosomal disorders, congenital heart disease other than PDA, contraindications to ibuprofen (e.g., renal failure, necrotizing enterocolitis), missing outcome data, or prior receipt of other PDA pharmacotherapy.

Intervention: Ibuprofen (oral or intravenous) at standard neonatal dosing (typically 10-5-5 mg/kg). Timing and duration as per clinical protocol.

Comparator: Expectant management - no routine pharmacological closure, allowing fluid restriction, diuretics, or supportive care alone.

Outcomes:

Primary: PDA closure (confirmed by echocardiography).

Secondary: BPD, mortality (all causes), pulmonary hypertension, renal insufficiency, neonatal pneumonia, ROP (any stage), IVH (any grade), pulmonary hemorrhage, gastrointestinal bleeding.

Data sources: Electronic medical records of Shengjing Hospital.

Statistical analysis:Descriptive statistics: frequencies, means (SD) or medians (IQR).

Bivariate comparisons: chi-square or Fisher's exact test for categorical variables; t-test or Mann-Whitney U test for continuous variables.

Multivariable logistic regression to estimate adjusted risk ratios (RR) and 95% confidence intervals for outcomes, adjusting for gestational age, sex, multiple gestation, and maternal factors (e.g., preeclampsia, chorioamnionitis).

Stratified analyses by gestational age subgroups.

Sensitivity analyses: excluding infants with protocol deviations or incomplete follow-up.

Ethical approval: Obtained from the Clinical Research Ethics Committee of Shengjing Hospital of China Medical University (approval number to be inserted). The study adheres to the Declaration of Helsinki.

Limitations: Single-center design, potential selection bias, residual confounding despite multivariable adjustment. Results may not be generalizable to other settings.

Dissemination: Results will be submitted for publication in a peer-reviewed journal.

• Study Type: Observational
• Enrollment (Actual): 541

Contacts and Locations

Study Locations

• China
  • Liaoning
    • Shenyang, Liaoning, China, 110004
      • Shengjing Hospital of China Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Preterm infants with hsPDA treated at a tertiary NICU in China. The cohort includes 541 infants: 241 received ibuprofen, 300 received expectant management. Gestational age subgroups: <28 weeks, 28-33 weeks, 33-37 weeks. Both sexes included. No healthy volunteers.

Description

Inclusion Criteria:

• - Preterm infants (gestational age <37 weeks) with echocardiographically confirmed hemodynamically significant patent ductus arteriosus (hsPDA)
• Admitted to the Department of Neonatology, Shengjing Hospital of China Medical University between June 2020 and June 2025

Exclusion Criteria:

• - Major congenital anomalies or chromosomal disorders
• Congenital heart disease other than PDA
• Contraindications to ibuprofen (e.g., renal failure, necrotizing enterocolitis)
• Missing outcome data
• Received other PDA pharmacotherapy before study intervention

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Ibuprofen Group; Preterm infants with hsPDA who received ibuprofen (oral or intravenous) at standard neonatal dosing. n=241.	Drug: Ibuprofen; No routine pharmacological closure; fluid restriction, diuretics, or supportive care only.
Expectant Management Group; Preterm infants with hsPDA who received no routine pharmacological closure, only fluid restriction, diuretics, or supportive care. n=300.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with PDA Closure	Proportion of preterm infants with echocardiographically confirmed closure of hemodynamically significant patent ductus arteriosus (hsPDA).	At day 7 after intervention start (or equivalent time point for expectant management group)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Bronchopulmonary Dysplasia (BPD)	Description: BPD defined as need for supplemental oxygen or respiratory support at 36 weeks postmenstrual age.	At 36 weeks postmenstrual age (measured between 35+0 and 36+6 weeks)
Number of Participants who Died (All-cause Mortality)	Death from any cause during the neonatal period.	From birth to hospital discharge, up to 28 days
Number of Participants with Pulmonary Hypertension	Echocardiographic evidence of elevated pulmonary artery pressure.	During initial hospitalization, up to 12 weeks
Number of Participants with Renal Insufficiency	Serum creatinine >1.5 mg/dL or oliguria (<1 mL/kg/h for 24 hours).	Within first 7 days after intervention start
Number of Participants with Neonatal Pneumonia	Clinical and radiographic diagnosis of pneumonia	During initial hospitalization, up to 12 weeks
Number of Participants with Retinopathy of Prematurity (ROP)	Any stage of ROP as diagnosed by ophthalmologic examination.	Prior to discharge or at 40 weeks postmenstrual age, up to 16 weeks
Number of Participants with Intraventricular Hemorrhage (IVH)	Any grade of IVH diagnosed by cranial ultrasound.	Within first 14 days of life
Number of Participants with Pulmonary Hemorrhage	Sudden deterioration with bloody tracheal aspirate confirmed by chest radiograph.	During initial hospitalization, up to 12 weeks
Number of Participants with Gastrointestinal Bleeding	Melena, hematemesis, or bloody gastric aspirate requiring intervention.	Within first 7 days after intervention start

Collaborators and Investigators

• Sponsor: Shengjing Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2020
• Primary Completion (Actual): June 30, 2025
• Study Completion (Actual): June 30, 2025

Study Registration Dates

• First Submitted: April 5, 2026
• First Submitted That Met QC Criteria: April 9, 2026
• First Posted (Actual): April 16, 2026

Study Record Updates

• Last Update Posted (Actual): April 16, 2026
• Last Update Submitted That Met QC Criteria: April 9, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: ibuprofen; preterm infants; bronchopulmonary dysplasia; PDA; expectant management; retrospective cohort
• Additional Relevant MeSH Terms: Urogenital Diseases; Cardiovascular Diseases; Female Urogenital Diseases and Pregnancy Complications; Heart Diseases; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Respiratory Tract Diseases; Lung Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Defects, Congenital; Lung Injury; Ventilator-Induced Lung Injury; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Premature Birth; Ductus Arteriosus, Patent; Bronchopulmonary Dysplasia; Organic Chemicals; Carboxylic Acids; Acids, Carbocyclic; Phenylpropionates; Ibuprofen
• Other Study ID Numbers: SJ-HSPDA-2020-2025; 82101813 (Other Grant/Funding Number: National Natural Science Foundation of China); 2024-MSLH-569 (Other Grant/Funding Number: Science and Technology Program of Liaoning Province); M0428 (Other Grant/Funding Number: 345 Talent Project of Shengjing Hospital)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared due to ethical and privacy restrictions. The study uses de-identified electronic medical records from a single hospital, and patient consent for data sharing was not obtained. Access to the data is governed by the hospital's ethics committee and institutional policies.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No