Conservative Management of Patent Ductus Arteriosus in Preterm Infants—A Systematic Review and Meta-Analyses Assessing Differences in Outcome Measures Between Randomized Controlled Trials and Cohort Studies

Objective: This study aims to evaluate outcome after conservative management (no pharmacological/surgical intervention other than fluid restriction, diuretics, or ventilator adjustments) compared with active (pharmacological and/or surgical) treatment for patent ductus arteriosus (PDA) in preterm infants and analyze differences in outcome between randomized controlled trials (RCTs) and cohort studies. Study Design: This is a systematic literature review using PubMed, EMBASE, and Cochrane library. RCTs and cohort studies comparing conservative management with active treatment were included. Meta-analysis was used to compare conservative management with any active (pharmacological and/or surgical), any pharmacological (non-prophylactic and prophylactic), and/or surgical treatment for mortality as primary and major neonatal morbidity as secondary outcome measure. Fixed-effect analysis was used, unless heterogeneity (I2) was >50%. Outcome is presented as relative risk (RR) with 95% confidence interval. Results: Twelve cohort studies and four RCTs were included, encompassing 41,804 and 720 patients, respectively. In cohort studies, conservative management for PDA was associated with a significantly higher risk for mortality (RR, 1.34 [1.12–1.62]) but a significantly lower risk for bronchopulmonary dysplasia (RR, 0.55 [0.46–0.65]), necrotizing enterocolitis (RR, 0.85 [0.77–0.93]), intraventricular hemorrhage (RR, 0.88 [0.83–0.95]), and retinopathy of prematurity (RR, 0.47 [0.28–0.79]) compared with any active PDA treatment. Meta-analysis of the RCTs revealed no significant differences in outcome between conservative management and active treatment. Conclusion: No differences in mortality or morbidity for conservative management compared with active treatment regimens were observed in RCTs. Findings from cohort studies mainly highlight the lack of high-quality evidence for conservative management for PDA in preterm infants.