Date	Event	Description
22 March 2018	New citation required and conclusions have changed	New citations, conclusions changed. For this update, we identified 6 new published studies. One study compared IV ibuprofen to placebo (Ding 2014); one study compared IV ibuprofen to IV indomethacin (Lin 2017); one study compared high versus standard dose of ibuprofen (Pourarian 2015); one study compared rectal versus oral ibuprofen (Demir 2017); one study compared IV ibuprofen to oral ibuprofen (Akar 2017) and one study compared IV ibuprofen to IV indomethacin( El‐Mashad 2017)
11 February 2018	New search has been performed	Thirty‐nine studies reporting on 2843 infants are included in this review. Currently there are at least 11 ongoing studies relevant to this review.
20 May 2015	Amended	Risk Difference fixed to Risk Ratio in data tables.
19 August 2014	New search has been performed	This updates the review "Ibuprofen for the treatment of patent ductus arteriosus in preterm and/or low birth weight infants" (Ohlsson 2013).
19 August 2014	New citation required but conclusions have not changed	For this update we identified 6 new studies and one follow‐up study from a previously reported trial. One study compared ibuprofen to placebo (Bagnoli 2013); one study compared continuous infusion of ibuprofen vs. bolus administration (Lago 2014); one study compared oral vs. iv administration of ibuprofen (Pistulli 2014); one study compared a high dose of ibuprofen vs. a standard dose of ibuprofen (Fesharaki 2012); one study compared standard vs. echocardiographically guided ibuprofen treatment (Bravo 2014); and one study compared oral ibuprofen with oral indomethacin for patent ductus arteriosus closure in preterm infants (Yadav 2014). One study reported on long‐term follow‐up in a limited cohort of an earlier published study (Gokmen 2011); Thirty‐three studies enrolling 2190 infants are included in this review. Currently there are at least four ongoing trials (Gournay 2012; Su 2010; Sung 2014; Yeh 2012).
16 November 2012	New citation required and conclusions have changed	This updates the review "Ibuprofen for the treatment of patent ductus arteriosus in preterm and/or low birth weight infants" (Ohlsson 2010). For this update six additional studies were included; one study compared oral ibuprofen with placebo (Lin 2012); three studies compared oral ibuprofen with iv ibuprofen (Cherif 2008; Erdeve 2012; Gokmen 2011, one study compared iv high dose of ibuprofen versus standard dose of ibuprofen (Dani 2012) and one study compared early versus expectant administration of iv ibuprofen (Sosenko 2012). Two studies are awaiting classification. The results, as before, show that ibuprofen is as effective as indomethacin in closing a patent ductus arteriosus (PDA). There is no statistically significant increase in the risk of chronic lung disease with ibuprofen. The incidence of necrotising enterocolitis is lowered by ibuprofen compared to indomethacin. Kidney function is less affected by ibuprofen than indomethacin and less by oral compared to intravenous (iv) ibuprofen. Oral ibuprofen may be more effective in closing a PDA than iv ibuprofen and reduces the risk of necrotising enterocolitis. Ibuprofen is now recommended over indomethacin to close a PDA. Additional studies are warranted to assess the effectiveness of high‐dose ibuprofen versus a standard dose regimen and early versus expectant administration of ibuprofen. Long‐term follow‐up studies are still warranted.
28 February 2010	New search has been performed	This updates the review "Ibuprofen for the treatment of patent ductus arteriosus in preterm and/or low birth weight infants" (Ohlsson 2008). This review was updated in February, 2010. One study comparing ibuprofen to placebo was identified and 5 new trials comparing ibuprofen to indomethacin were identified. The results, as before, show that ibuprofen is as effective as indomethacin in closing a PDA. There is now clearly no statistically significant increase in the risk of chronic lung disease with ibuprofen. A new important finding is that ibuprofen reduces the risk of necrotizing enterocolitis. Ibuprofen is now recommended over indomethacin to close a PDA. Long‐term follow‐up studies are still warranted.
26 June 2008	Amended	Converted to new review format.
19 September 2007	New search has been performed	This review updates the existing review "Ibuprofen for the treatment of patent ductus arteriosus in preterm and/or low birth weight infants", published in Issue 4, 2005 of The Cochrane Library (Ohlsson 2005). This update of the review conducted in August 2007 identified four previously not included trials (Adamska 2005, Aly 2007, Gimeno Navarro 2005, Pezzati 1999). In addition, two trials previously included as abstracts have now been published as full articles (Chotigeat 2003, Supapannachart 2002). The current review includes a total of 16 trials enrolling 876 infants. The increase in sample size made the point estimates more precise and changed the results of one important outcome. In the previous review there was a statistically significant increase in chronic lung disease in the ibuprofen group. Although a trend towards an increase in chronic lung disease remained in this review, the summary estimates did not reach statistical significance. In this review, the outcome of serum/plasma levels of creatinine following treatment was included and the results showed significantly lower levels in the ibuprofen group. As in previous reviews, the risk of decreased urine output was lower in the ibuprofen group. There is not enough data available regarding the effectiveness of oral ibuprofen to close a patent ductus arteriosus. One case of pulmonary hypertension associated with ibuprofen treatment was reported in one trial. Long‐term neurodevelopmental data are still lacking. Based on the available evidence clinicians may prefer one of the two drugs currently available for closure of a patent ductus arterious over the other: a) Either drug is effective in closing a patent ductus arterious b) Ibuprofen may be preferred because of its less negative impact on the kidney function c) Indomethacin may be preferred because of the trend towards increase in chronic lung disease in the ibuprofen group and the potential risk of pulmonary hypertension associated with the use of ibuprofen This review has previously been updated in 2005 (Ohlsson 2005). An updated search in July 2005 identified one trial of ibuprofen versus placebo, but the results were not reported unblinded to group. However, the search identified three trials that compared ibuprofen to indomethacin for the treatment of a PDA. The addition of the results from these three trials confirmed our previous findings that ibuprofen is no more effective than indomethacin and may cause more adverse effects. There were no important changes to the conclusions of that review. An updated search in October 2004 found no new eligible trials for inclusion in this review. There was no trial identified using mefenamic acid in the original review or in any of the updates.
19 September 2007	New citation required and conclusions have changed	Substantive amendment