Use of ibuprofen for the closure of patent ductus arteriosus in preterm infants: a systematic review of meta-analyses.

To systematically review ibuprofen, including versus indomethacin and paracetamol/acetaminophen, for the closure of patent ductus arteriosus (PDA). Pubmed, Embase, Cochrane and gray literature were searched to summarize ibuprofen outcomes in closure of PDA in published meta-analyses (MAs). Seven MAs were included. Including high dose (HD) use, ibuprofen is equivalent/superior to indomethacin, and inferior/equivalent to paracetamol. Oral ibuprofen had higher efficacy than IV ibuprofen, including compared with indomethacin and paracetamol. Ibuprofen had safety advantages over indomethacin. Indomethacin and paracetamol had safety advantages over IV ibuprofen. HD of ibuprofen increases efficacy, but not toxicity. Evidence on ibuprofen effectiveness and safety, including the dosage forms, is limited by heterogeneity in doses and the levels of methods quality and risk of bias.