Comparative safety and efficacy of paracetamol versus non‐steroidal anti‐inflammatory agents in neonates with patent ductus arteriosus: A systematic review and meta‐analysis of randomized controlled trials

Aim Ibuprofen and indomethacin are the preferred drug treatment for patent ductus arteriosus (PDA) in preterm neonates. The comparative safety and efficacy of paracetamol as an alternative has not yet been well established. The aim of our study was to define the comparative efficacy and safety of paracetamol versus ibuprofen and indomethacin for PDA. Methods We performed a systematic literature search in PubMed, Scopus and Cochrane databases on randomized controlled trials comparing the efficacy and/or the safety of paracetamol versus ibuprofen and/or indomethacin and meta‐analysed the available data. Results There were 1718 neonates from 20 eligible studies. Paracetamol did not differ from ibuprofen or indomethacin regarding the primary (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.69–1.26, P ‐value: 0.650, when compared to ibuprofen, and OR: 0.78; 95% CI: 0.20–3.02, P ‐value: 0.716, when compared to indomethacin) and overall (OR: 1.17; 95% CI: 0.82–1.66, P ‐value: 0.394, when compared to ibuprofen, and OR: 1.12; 95% CI: 0.58–2.15, P ‐value: 0.733, when compared to indomethacin) PDA closure rates. Paracetamol resulted in significantly reduced risk of oliguria and a tendency towards less gastrointestinal bleeding. Conclusion There was no significant difference between paracetamol and ibuprofen or indomethacin in the PDA closure rates. However, paracetamol caused fewer adverse effects.