Use of ibuprofen for the closure of patent ductus arteriosus in preterm infants: a systematic review of meta-analyses
Publication: Journal of Comparative Effectiveness Research
Abstract
Aim: To systematically review ibuprofen, including versus indomethacin and paracetamol/acetaminophen, for the closure of patent ductus arteriosus (PDA). Methods: Pubmed, Embase, Cochrane and gray literature were searched to summarize ibuprofen outcomes in closure of PDA in published meta-analyses (MAs). Results: 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. Conclusion: 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.
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References
Papers of special note have been highlighted as: • of interest
1.
Gillam-Krakauer M, Reese J. Diagnosis and management of patent ductus arteriosus. NeoReviews 19(7), e394–e402 (2018).
2.
Yanagi R, Wilson A, Newfeld E, Aziz K, Hunt C. Indomethacin treatment for symptomatic patent ductus arteriosus: a double-blind control study. Pediatrics 67(5), 647–652 (1981).
3.
Nestrud R, Hill D, Arrington R et al. Indomethacin treatment in patent ductus arteriosus. A double-blinded study utilizing indomethacin plasma levels. Dev. Pharmacol. Ther. 1(2–3), 125–136 (1980).
4.
Gersony WM, Peckham GJ, Ellison RC, Miettinen OS, Nadas AS. Effects of indomethacin in premature infants with patent ductus arteriosus: results of a national collaborative study. J. Pediatr. 102, 895–906 (1983).
5.
Ohlsson A, Walia R, Shah S. Ibuprofen for the treatment of patent ductus arteriosus in preterm and/or low birth weight infants. Cochrane Database Syst. Rev. (2), CD003481 (2003).
6.
Hammerman C, Bin-Nun A, Markovitch E, Schimmel MS, Kaplan M, Fink D. Ductal closure with paracetamol: a surprising new approach to patent ductus arteriosus treatment. Pediatrics 128, e1618–e1621 (2011).
7.
Erdeve O, Yurttutan S, Altug N et al. Oral versus intravenous ibuprofen for patent ductus arteriosus closure: a randomized controlled trial in extremely low birthweight infants. Arch. Dis. Child. Fetal Neonatal Ed. 97(4), F279–F283 (2012).
8.
Hunt H, Pollock A, Campbell P, Estcourt L, Brunton G. An introduction to overviews of reviews: planning a relevant research question and objective for an overview. Syst. Rev. 7(1), 39 (2018).
9.
Abdelaal M, Abushanab D, Al-Badriyeh D. Surfactant therapy for meconium aspiration syndrome in neonates: a systematic overview of systematic reviews and recent clinical trials. J. Comp. Eff. Res. 9(8), 527–536 (2020).
10.
Shea BJ, Reeves BC, Wells G et al. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomized or non-randomized studies of healthcare interventions, or both. BMJ 358, j4008 (2017).
11.
Yang F, Wang H, Zou J et al. Assessing the methodological and reporting quality of network meta-analyses in Chinese medicine. Medicine (Baltimore) 97(47), e13052 (2018).
12.
Whiting P, Savović J, Higgins JP et al. ROBIS: a new tool to assess risk of bias in systematic reviews was developed. J. Clin. Epidemiol. 69, 225–234 (2016).
13.
Ohlsson A, Walia R, Shah S. Ibuprofen for the treatment of patent ductus arteriosus in preterm or low birth weight (or both) infants. Cochrane Database Syst. Rev. 2(2), CD003481 (2020).
• A high methods quality and low risk of bias meta-analysis. The meta-analysis is of randomized controlled trials that compare between ibuprofen and indomethacin, based on separate or mixed dosage form regimens. This included 42 studies.
14.
Ohlsson A, Walia R, Shah S. Ibuprofen for the treatment of patent ductus arteriosus in preterm and/or low birth weight infants. Cochrane Database Syst. Rev. (4), CD003481 (2005).
15.
Ohlsson A, Walia R, Shah S. Ibuprofen for the treatment of patent ductus arteriosus in preterm and/or low birth weight infants. Cochrane Database Syst. Rev. (1), CD003481 (2008).
16.
Ohlsson A, Walia R, Shah SS. Ibuprofen for the treatment of patent ductus arteriosus in preterm and/or low birth weight infants. Cochrane Database Syst. Rev. (4), CD003481 (2010).
17.
Ohlsson A, Shah SS. Ibuprofen for the prevention of patent ductus arteriosus in preterm and/or low birth weight infants. Cochrane Database Syst. Rev. (7), CD004213 (2011).
18.
Ohlsson A, Walia R, Shah SS. Ibuprofen for the treatment of patent ductus arteriosus in preterm and/or low birth weight infants. Cochrane Database Syst. Rev. (4), CD003481 (2013).
19.
Ohlsson A, Shah PS. Paracetamol (acetaminophen) for patent ductus arteriosus in preterm and/or low-birth-weight infants. Cochrane Database Syst. Rev. (9), CD010061 (2012).
20.
Ohlsson A, Shah PS. Paracetamol (acetaminophen) for patent ductus arteriosus in preterm or low-birth-weight infants. Cochrane Database Syst. Rev. (3), CD010061 (2015).
21.
Ohlsson A, Shah P. Paracetamol (acetaminophen) for patent ductus arteriosus in preterm or low birth weight infants. Cochrane Database Syst. Rev. 1(1), CD010061 (2020).
• A high methods quality and low risk of bias meta-analysis. The meta-analysis is of randomized controlled trials that compare among paracetamol and ibuprofen/indomethacin, based on separate dosage form regimens. This included seven clinical trials.
22.
Mitra S, Florez ID, Tamayo ME et al. Association of placebo, indomethacin, ibuprofen, and acetaminophen with closure of hemodynamically significant patent ductus arteriosus in preterm infants. JAMA 319, 1221 (2018).
• A moderate methods quality and low risk of bias meta-analysis. The meta-analysis is of randomized controlled trials that compare among ibuprofen, paracetamol, and indomethacin, based on separate dosage form regimens and a variety of dose levels. This included 70 clinical trials.
23.
Marconi E, Bettiol A, Ambrosio G et al. Efficacy and safety of pharmacological treatments for patent ductus arteriosus closure: a systematic review and network meta-analysis of clinical trials and observational studies. Pharmacol. Res. 148, 104418 (2019).
• A low methods quality and unclear risk of bias network meta-analysis. The network meta-analysis is of randomized controlled trials and observational studies that compare among ibuprofen, paracetamol, and indomethacin, based on mixed dosage form regimen administrations. This included 61 clinical trials and observational studies.
24.
Jones LJ, Craven PD, Attia J, Thakkinstian A, Wright I. Network meta-analysis of indomethacin versus ibuprofen versus placebo for PDA in preterm infants. Arch. Dis. Child. Fetal Neonatal Ed. 96, F45–F52 (2011).
• A low methods quality and high risk of bias network meta-analysis. The network meta-analysis is of randomized controlled trials that compare among ibuprofen and indomethacin, based on separate dosage form regimens. This included 20 clinical trials.
25.
Huang X, Wang F, Wang K. Paracetamol versus ibuprofen for the treatment of patent ductus arteriosus in preterm neonates: a meta-analysis of randomized controlled trials. J. Matern. Neonatal Med. 31, 2216–2222 (2018).
• A low methods quality and high risk of bias meta-analysis. The meta-analysis is of randomized controlled trials that compare oral versus intravenous ibuprofen administrations. This included four clinical trials.
26.
Loomba R, Nijhawan K. Ibuprofen versus indomethacin for medical closure of the patent arteriald duct: a pooled analysis by route of administration. Cureus 7(6), e274 (2015).
• A critically low methods quality and high risk of bias meta-analysis. The meta-analysis is of randomized controlled trials and observational studies that compare between ibuprofen and indomethacin, based on mixed dosage form regimen administrations. This included 22 clinical trials and observational studies.
27.
Cherif A, Khrouf N, Jabnoun S. Randomized pilot study comparing oral ibuprofen with intravenous ibuprofen in very low birth weight infants with patent ductus arteriosus. Pediatrics 122, e1256–e1261 (2008).
28.
Dornelles LV, Corso AL, Silveira Rde C. Comparison of two dose regimens of ibuprofen for the closure of patent ductus arteriosus in preterm newborns. J. Pediatr. 92, 314–318 (2016).
29.
Hamrick SE, Hansmann G. Patent ductus arteriosus of the preterm infant. Pediatrics 125, 1020–1030 (2010).
30.
Akar M, Yildirim TG, Sandal G. Does ibuprofen treatment in patent ductus arteriosus alter oxygen free radicals in premature infants? Cardiol. Young 27, 507–511 (2017).
31.
Van Overmeire B, Smets K, Lecoutere D et al. A comparison of ibuprofen and indomethacin for closure of patent ductus arteriosus. N. Engl. J. Med. 343(10), 674–681 (2000).
32.
Shah SS, Ohlsson A. Ibuprofen for the prevention of patent ductus arteriosus in preterm and/or low birth weight infants. Cochrane Database Syst. Rev. (1), CD004213 (2006).
33.
Chotigeat U, Jirapapa K, Layangkool T. A comparison of oral ibuprofen and intravenous indomethacin for closure of patent ductus arteriosus in preterm infants. J. Med. Assoc. Thai. 86, 563–569 (2003).
34.
Supapannachart S, Limrungsikul A, Khowsathit P. Oral ibuprofen and indomethacin for treatment of patent ductus arteriosus in premature infants: a randomized trial at Ramathibodi Hospital. J. Med. Assoc. Thai. 85, 1252–1258 (2002).
35.
Erdeve O, Gokmen T, Altug N, Dilmen U. Oral versus intravenous ibuprofen: which is better in closure of patent ductus arteriosus? Pediatrics 123, 763 (2009).
36.
Akisu M, Ozyurek AR, Dorak C, Parlar A, Kultursay N. Enteral ibuprofen versus indomethacin in the treatment of PDA in preterm newborn infants. Turk Pediatr. J. 44, 56–60 (2001).
37.
Arslan M, Olukman O, Calkavur S, Atlihan F, Mese T, Ozturk IC. The efficacy of oral ibuprofen in the treatment of clinically significant patent ductus arteriosus in preterm infants. Turk. Arch. Pediatr. 45, 329–333 (2010).
38.
Aly H, Lotly W, Badrawi N, Ghawas M, Abdel-Meguid IE, Hammad TA. Oral ibuprofen and ductus arteriosus in premature infants: a randomized pilot study. Am. J. Perinatol. 24, 267–270 (2007).
39.
Cherif A, Jabnoun S, Khrouf N. Oral ibuprofen in early curative closure of patent ductus arteriosus in very premature infants. Am. J. Perinatol. 24, 339–345 (2007).
40.
Hairprasad P, Sundarrajan V, Srimathy G, Suthager B, Ramadevi BS. Oral ibuprofen for closure of hemodynamically significant PDA in premature neonates. Indian Pediatr. 39, 99–100 (2002).
41.
Heyman E, Morag I, Batash D, Keidar R, Baram S, Berkovitch M. Closure of patent ductus arteriosus with oral ibuprofen suspension in premature newborns: a pilot study. Pediatrics 112, 354 (2003).
42.
Koehne PS, Bein G, Alexi-Meskhishwili V, Weng Y, Bührer C, Obladen M. Patent ductus arteriosus in very low birth weight infants: complications of pharmacological and surgical treatment. J. Perinat. Med. 29, 327–334 (2001).
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Pages: 549 - 568
PubMed: 33880942
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© 2021 Future Medicine Ltd.
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Received: 29 October 2020
Accepted: 23 February 2021
Published online: 21 April 2021
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Qatar University: QUST-1-CPH-2020-1
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Use of ibuprofen for the closure of patent ductus arteriosus in preterm infants: a systematic review of meta-analyses. (2021) Journal of Comparative Effectiveness Research. DOI: 10.2217/cer-2020-0235
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