Related Experiment Video
Updated: Aug 8, 2026
Hemodynamic Precision in the Neonatal Intensive Care Unit using Targeted Neonatal Echocardiography
Published on: January 27, 2023
Active pharmacotherapy versus expectant management of patent ductus arteriosus in extremely preterm infants: a
Shripada C Rao1,2, Chandra Rath3, Sanjay Patole2,4
1Perth Children's Hospital Neonatal Intensive Care Unit, Nedlands, Western Australia, Australia shripada.rao@health.wa.gov.au.
Insights
Active pharmacotherapy for patent ductus arteriosus (PDA) in extremely preterm infants increases mortality risk. Expectant management is a safer alternative, warranting careful consideration for treatment decisions in neonates.
Area of Science:
- Neonatal Medicine
- Pediatric Cardiology
- Pharmacology
Background:
- Patent ductus arteriosus (PDA) is common in extremely preterm infants.
- Current treatment often involves active pharmacotherapy based on echocardiography.
- The safety and efficacy of this approach require rigorous evaluation.
Purpose of the Study:
- To compare active pharmacotherapy with expectant management for PDA in extremely preterm infants.
- To assess the impact on mortality and chronic lung disease (CLD).
- To provide evidence for optimizing treatment strategies.
Main Methods:
- Systematic review and meta-analysis of randomized controlled trials (RCTs).
- Inclusion of 12 RCTs with 2344 infants (<29 weeks gestation).
- Trial sequential analysis (TSA) to confirm findings.
Main Results:
- Active pharmacotherapy showed a statistically significant increase in mortality (RR 1.34).
- The number needed to harm for mortality was 25.
- No significant difference in chronic lung disease (CLD) was observed (RR 0.99).
- High certainty of evidence for mortality, moderate for CLD.
Conclusions:
- Active pharmacotherapy for PDA in extremely preterm infants is associated with increased mortality.
- Clinically significant harm necessitates careful consideration of treatment benefits versus risks.
- Findings support informed decision-making and parental discussions regarding PDA management.
Objectives:
To assess the effectiveness and safety of active pharmacotherapy for patent ductus arteriosus (PDA) initiated based on echocardiography-criteria versus expectant management in extremely preterm infants <29 w gestation in the first three weeks of life.
Study Design:
Systematic review with meta-analysis and trial sequential analysis (TSA). We searched PubMed, Embase, CENTRAL and Emcare for randomised trials published between 2010 and May 2026. We synthesised results using random-effects meta-analysis and conducted a TSA.
Patients:
Extremely preterm infants with PDA considered as significant on echocardiography.
Interventions:
Pharmacotherapy versus expectant management.
Main Outcome Measures:
Mortality by 36 weeks postconceptional age or before discharge and chronic lung disease (CLD).
Results:
We included 12 trials involving 2344 extremely preterm infants. Meta-analysis found increased risk of mortality with active pharmacotherapy (RR 1.34, 95% CI 1.08 to 1.67; p=0.008, I2=0%; 12 randomised controlled trials (RCTs)). Number-needed-to-treat for an additional harmful outcome (i.e. mortality) was 25 (95% CI 17 to 100). On TSA conducted with the stringent alpha error 3.3% and beta 10%, the cumulative Z-score touched the O'Brien-Fleming monitoring boundary at the current sample size, supporting the meta-analysis findings under the specified TSA assumptions.For CLD, meta-analysis showed little or no difference (RR 0.99, 95% CI 0.92 to 1.06, p=0.74, I2=14%, 12 RCTs). The certainty of evidence was high for mortality and moderate for CLD.
Conclusions:
In extremely preterm infants, active pharmacotherapy for PDA based on current echocardiographic criteria in the first three weeks of life was associated with increased mortality with a clinically important number needed to harm. These findings should inform treatment decisions and discussions with parents while ongoing research seeks to identify infants who may benefit from treatment.
Prospero Registration Number:
CRD420261303992.