Pharmacological treatment of patent ductus arteriosus and mortality risk in preterm infants: a Bayesian meta-analysis across gestational age groups.

BACKGROUND: Recent randomised controlled trials and meta-analyses have questioned the safety of early pharmacological treatment of patent ductus arteriosus in preterm infants, suggesting possible increases in the risk of mortality and bronchopulmonary dysplasia. Whether these risks vary by gestational age remains uncertain. We aimed to compare the effects of pharmacological patent ductus arteriosus treatment in infants with a gestational age less than 26 weeks versus those with a gestational age of 26 weeks or greater. METHODS: For this Bayesian model-averaged meta-analysis, we searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) for randomised controlled trials enrolling infants with a gestational age less than 32 weeks and echocardiographically confirmed patent ductus arteriosus who were randomly assigned either to pharmacological treatment or to placebo or expectant management. The primary outcome was all-cause mortality before 36 weeks' postmenstrual age and secondary outcomes were moderate-to-severe bronchopulmonary dysplasia and the composite of death or moderate-to-severe bronchopulmonary dysplasia at 36 weeks' postmenstrual age. Pooled risk ratios (RRs) with 95% credible intervals (CrIs) were estimated. RRs greater than 1 indicated harm. We calculated the posterior probability of harm (Prharm=P[logRR>0]) and Bayes factors comparing harm versus benefit (BFharm/benefit). This study is registered on PROSPERO (CRD42024622527). FINDINGS: Ten randomised controlled trials including 2365 infants (1133 female and 1232 male) were analysed; 1045 had a gestational age less than 26 weeks. Pharmacological treatment was associated with increased mortality in infants with a gestational age less than 26 weeks (RR 1·12 [95% CrI 0·90-1·41], Prharm=0·85, BFharm/benefit=5·48), in those with a gestational age of 26 weeks or greater (1·22 [0·90-1·77], Prharm=0·89, BFharm/benefit=7·82), and in the overall population (1·23 [95% CrI 1·00-1·54], Prharm=0·97, BFharm/benefit=36·04). For bronchopulmonary dysplasia and the composite outcome of death or moderate-to-severe bronchopulmonary dysplasia, analyses explicitly incorporating the possibility of no effect indicated that the data were more consistent with the no-effect model than with either the benefit or the harm model. INTERPRETATION: The currently available randomised evidence is consistent with an increased mortality risk associated with pharmacological patent ductus arteriosus treatment, without evidence of a compensatory reduction in bronchopulmonary dysplasia. This association was evident both below and above the 26-week gestational age threshold. These findings question the safety of routine pharmacological treatment and underscore the need for more selective, evidence-based approaches for patent ductus arteriosus management. FUNDING: None.