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Intervention Review

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Ibuprofen for the treatment of patent ductus arteriosus in preterm and/or low birth weight infants

  1. Arne Ohlsson1,*,
  2. Rajneesh Walia2,
  3. Sachin S Shah3

Editorial Group: Cochrane Neonatal Group

Published Online: 30 APR 2013

Assessed as up-to-date: 16 JUL 2012

DOI: 10.1002/14651858.CD003481.pub5


How to Cite

Ohlsson A, Walia R, Shah SS. Ibuprofen for the treatment of patent ductus arteriosus in preterm and/or low birth weight infants. Cochrane Database of Systematic Reviews 2013, Issue 4. Art. No.: CD003481. DOI: 10.1002/14651858.CD003481.pub5.

Author Information

  1. 1

    University of Toronto, Departments of Paediatrics, Obstetrics and Gynaecology and Institute of Health Policy, Management and Evaluation, Toronto, Ontario, Canada

  2. 2

    University of Birmingham and Walsall Manor Hospital, Paediatrics/Neonatology, Walsall, West Midlands, UK

  3. 3

    Aditya Birla Memorial Hospital, Neonatal and Pediatric Intensive Care Services, Pune, India

*Arne Ohlsson, Departments of Paediatrics, Obstetrics and Gynaecology and Institute of Health Policy, Management and Evaluation, University of Toronto, 600 University Avenue, Toronto, Ontario, M5G 1X5, Canada. aohlsson@mtsinai.on.ca.

Publication History

  1. Publication Status: New search for studies and content updated (conclusions changed)
  2. Published Online: 30 APR 2013

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This is not the most recent version of the article. View current version (18 FEB 2015)

 

Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary

Background

Indomethacin is used as standard therapy to close a patent ductus arteriosus (PDA) but is associated with reduced blood flow to several organs. Ibuprofen, another cyclo-oxygenase inhibitor, may be as effective as indomethacin with fewer side effects.

Objectives

To determine the efficacy and safety of ibuprofen for closing a PDA in preterm and/or low birth weight infants. Seperate comparisons are presented for 1. ibuprofen (iv) compared with placebo; 2. ibuprofen (oral) compared with placebo; 3. ibuprofen (oral or iv) compared with other cyclo-oxygenase inhibitors (given iv or orally); 4. ibuprofen (oral) versus indomethacin (given iv or orally); 5. ibuprofen (oral) versus iv ibuprofen; 6. high dose versus standard dose of iv ibuprofen; 7. early versus expectant administration of iv ibuprofen.

Search methods

We searched The Cochrane Library, MEDLINE, EMBASE, Clincialtrials.gov, Controlled-trials.com, www.abstracts2view.com/pas, and personal files in July 2012.

Selection criteria

Randomised or quasi-randomised controlled trials of ibuprofen for the treatment of a PDA in newborn infants.

Data collection and analysis

Data collection and analysis conformed to the methods of the Cochrane Neonatal Review Group.

Main results

Twenty-seven studies are included in this review. One study (n = 136) compared iv ibuprofen versus placebo. Ibuprofen reduced the composite outcome of infant deaths, infants who dropped out or required rescue treatment; risk ratio (RR) 0.58 (95% confidence interval (CI) 0.38 to 0.89); risk difference (RD) -0.22 (95% CI -0.38 to -06); number needed to benefit (NNTB) 5 (95% CI 3 to 17). One study (n = 64) compared oral ibuprofen with placebo. There was a significant reduction in the failure rate to close a PDA; RR 0.26 (95% CI 0.11 to 0.62); RD -0.44 (95% CI -0.65 to -0.23); NNTB 2 (95% CI 2 to 4). Failure rates for PDA closure with ibuprofen (oral or iv) compared with indomethacin (oral or iv) was reported in 20 studies (n = 1019 infants). There was no significant difference between the groups; typical RR 0.98 (95% CI 0.80 to 1.20) I2 = 0%; typical RD -0.01 (95% CI -0.06 to 0.05); I2 = 0%. The risk of developing necrotising enterocolitis (NEC) was reduced for ibuprofen (15 studies (n = 865); typical RR 0.68 (95% CI 0.47 to 0.99); typical RD -0.04 (95% CI -0.08 to -0.00; (P = 0.04); NNTB 25 (95% CI 13, infinity); I2 = 0%). The duration of ventilatory support was reduced with ibuprofen (oral or iv) compared with iv or oral indomethacin (six studies, n = 471) mean difference (MD) -2.35 days (95% CI -3.71 to -0.99); I2 = 19%. Failure rates for PDA closure with oral ibuprofen compared with indomethacin (oral or iv) were reported in seven studies (n = 189 infants). There was no significant difference between the groups; typical RR 0.82 (95% CI 0.52 to 1.29); typical RD -0.06 (95% CI -0.18 to 0.06). The risk of NEC was reduced with oral ibuprofen compared with indomethacin (oral or iv) six studies (n = 166); typical RR 0.44 (95% CI 0.23 to 0.82); RD -0.15 (95% CI -0.25 to -0.04); NNTB 7 (95% CI 4 to 25). There was no heterogeneity for this outcome. There was a decreased risk of failure to close a PDA with oral ibuprofen compared with iv ibuprofen, three studies (n = 236) typical RR 0.37 (95% CI 0.23 to 0.61); typical RD -0.24 (95% CI -0.35 to -0.13); NNTB 4 (95% CI 3 to 8). There was less evidence of transient renal insufficiency in infants who received ibuprofen compared with indomethacin. High dose versus standard dose of iv ibuprofen and early versus expectant administration of iv ibuprofen have only been studied in two trials.

Authors' conclusions

Ibuprofen is as effective as indomethacin in closing a PDA and reduces the risk of NEC and transient renal insufficiency. Given the reduction in NEC ibuprofen currently appears to be the drug of choice. Oro-gastric administration of ibuprofen appears at least as effective as iv administration. Too few patients have been enrolled in studies assessing the effectiveness of a high dose of ibuprofen versus the standard dose and early versus expectant administration of ibuprofen to make recommendations. Studies are needed to evaluate the effect of ibuprofen compared with indomethacin treatment on longer-term outcomes in infants with PDA.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary

Ibuprofen for the treatment of patent ductus arteriosus in preterm and/or low birth weight infants

A common complication for very preterm (premature) or very small babies is PDA (patent ductus arteriosus). PDA is an open channel between the lungs and heart. It should close after birth, but sometimes remains open because of the baby's premature stage of development. PDA can lead to life-threatening complications. The usual treatment for PDA has been indomethacin, a drug that will successfully close the PDA in the majority of cases, but can cause serious adverse effects. Another option is the drug ibuprofen. This review of 27 trials found that ibuprofen is as effective as indomethacin to close a PDA and causes fewer transient adverse effects on the kidneys and reduces the risk of necrotising enterocolitis, a serious condition that affects the gut. Whether ibuprofen confers any important long-term advantages on development or not is not known. Long-term follow-up studies to 18 months of age and to the age of school entry are needed to decide whether ibuprofen or indomethacin is the drug of choice for closing a PDA.