Infant, Premature, Patent Ductus Arteriosus
Conditions
Keywords
ibuprofen, expectant management, preterm infants, retrospective cohort, PDA, bronchopulmonary dysplasia
Brief summary
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.
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.
Interventions
DRUGIbuprofen
No routine pharmacological closure; fluid restriction, diuretics, or supportive care only.
Sponsors
Shengjing Hospital
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
23 Weeks to 37 Weeks
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with PDA Closure | At day 7 after intervention start (or equivalent time point for expectant management group) | Proportion of preterm infants with echocardiographically confirmed closure of hemodynamically significant patent ductus arteriosus (hsPDA). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Bronchopulmonary Dysplasia (BPD) | At 36 weeks postmenstrual age (measured between 35+0 and 36+6 weeks) | Description: BPD defined as need for supplemental oxygen or respiratory support at 36 weeks postmenstrual age. |
| Number of Participants who Died (All-cause Mortality) | From birth to hospital discharge, up to 28 days | Death from any cause during the neonatal period. |
| Number of Participants with Pulmonary Hypertension | During initial hospitalization, up to 12 weeks | Echocardiographic evidence of elevated pulmonary artery pressure. |
| Number of Participants with Renal Insufficiency | Within first 7 days after intervention start | Serum creatinine \>1.5 mg/dL or oliguria (\<1 mL/kg/h for 24 hours). |
| Number of Participants with Neonatal Pneumonia | During initial hospitalization, up to 12 weeks | Clinical and radiographic diagnosis of pneumonia |
| Number of Participants with Retinopathy of Prematurity (ROP) | Prior to discharge or at 40 weeks postmenstrual age, up to 16 weeks | Any stage of ROP as diagnosed by ophthalmologic examination. |
| Number of Participants with Intraventricular Hemorrhage (IVH) | Within first 14 days of life | Any grade of IVH diagnosed by cranial ultrasound. |
| Number of Participants with Pulmonary Hemorrhage | During initial hospitalization, up to 12 weeks | Sudden deterioration with bloody tracheal aspirate confirmed by chest radiograph. |
| Number of Participants with Gastrointestinal Bleeding | Within first 7 days after intervention start | Melena, hematemesis, or bloody gastric aspirate requiring intervention. |
Countries
China
Outcome results
None listed