Beneficial vs harmful effects of pharmacological treatment of patent ductus arteriosus: A Bayesian meta-analysis

Background: Randomized controlled trials (RCTs) have failed to demonstrate the beneficial effects of the pharmacological treatment of patent ductus arteriosus (PDA) in preterm infants. We conducted a Bayesian model averaged (BMA) meta-analysis of RCTs comparing the pharmacological treatment of PDA with placebo or expectant treatment. Methods: We searched for RCTs including infants with gestational age (GA) <= 32 weeks and with a rate of open-label treatment of less than 25% in the control arm. The primary outcome was mortality and secondary outcomes included bronchopulmonary dysplasia (BPD). We calculated Bayes factors (BFs). The BF+/- is the ratio of the probability of the data under H+ (pharmacological treatment is beneficial) over the probability of the data under H- (pharmacological treatment is harmful). Results: Five RCTs were included (1341 infants). BMA showed strong evidence in favor of the harmful effect of medication for BPD (BF+/- = 0.02) and BPD or death (BF+/- = 0.03). When the two largest trials, which used early (<72 h) ibuprofen in infants with GA <= 28 weeks, were pooled, the BMA demonstrated moderate evidence in favor of higher mortality in the medication group (BF+/- = 0.24). Conclusion: Pharmacological treatment of PDA in extremely preterm infants may result in more complications than clinical benefit. Impact: Randomized controlled trials spanning several decades have investigated the pharmacological treatment of patent ductus arteriosus (PDA) but have failed to demonstrate an improvement in mortality or short-term morbidity. We conducted a Bayesian meta-analysis to answer the question: Is the pharmacological treatment of PDA beneficial or harmful in very and extremely preterm infants? Bayesian meta-analysis showed strong evidence in favor of higher rates of bronchopulmonary dysplasia (BPD) and death or BPD in infants receiving pharmacological treatment of PDA when compared with infants receiving placebo or expectant management. Pharmacological treatment of PDA in extremely preterm infants may result in more complications than clinical benefit.