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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)

[Figure 1]
Figure 1. Forest plot of comparison: 3 Intravenous or oral ibuprofen versus iv or oral indomethacin, outcome: 3.1 Failure to close a PDA (after single or three doses).
[Figure 2]
Figure 2. Forest plot of comparison: 3 Intravenous or oral ibuprofen versus iv or oral indomethacin, outcome: 3.17 Necrotizing enterocolitis (any stage).
[Figure 3]
Figure 3. Forest plot of comparison: 4 Oral ibuprofen versus iv or oral indomethacin, outcome: 4.1 Failure to close a PDA (after three doses).
[Figure 4]
Figure 4. Forest plot of comparison: 4 Oral ibuprofen versus iv or oral indomethacin, outcome: 4.18 Necrotizing enterocolitis (any stage).
[Figure 5]
Figure 5. Forest plot of comparison: 5 Oral ibuprofen versus iv ibuprofen, outcome: 5.1 Failure to close a PDA (after single or three doses).
[Figure 6]
Figure 6. Funnel plot of comparison: 3 Intravenous or oral ibuprofen versus iv or oral indomethacin, outcome: 3.1 Failure to close a PDA (after single or three doses).
[Analysis 1.1]
Analysis 1.1. Comparison 1 Intravenous ibuprofen versus placebo or no drug, Outcome 1 Infant deaths, infants who dropped out or required rescue treatment.
[Analysis 1.2]
Analysis 1.2. Comparison 1 Intravenous ibuprofen versus placebo or no drug, Outcome 2 NEC.
[Analysis 1.3]
Analysis 1.3. Comparison 1 Intravenous ibuprofen versus placebo or no drug, Outcome 3 Intraventricular haemorrhage (any grade).
[Analysis 1.4]
Analysis 1.4. Comparison 1 Intravenous ibuprofen versus placebo or no drug, Outcome 4 Intraventricular haemorrhage (grades III-IV).
[Analysis 1.5]
Analysis 1.5. Comparison 1 Intravenous ibuprofen versus placebo or no drug, Outcome 5 Pulmonary haemorrhage.
[Analysis 1.6]
Analysis 1.6. Comparison 1 Intravenous ibuprofen versus placebo or no drug, Outcome 6 Pulmonary hypertension.
[Analysis 1.7]
Analysis 1.7. Comparison 1 Intravenous ibuprofen versus placebo or no drug, Outcome 7 ROP (any stage).
[Analysis 1.8]
Analysis 1.8. Comparison 1 Intravenous ibuprofen versus placebo or no drug, Outcome 8 ROP (stage 3 or 4).
[Analysis 1.9]
Analysis 1.9. Comparison 1 Intravenous ibuprofen versus placebo or no drug, Outcome 9 ROP (plus disease).
[Analysis 1.10]
Analysis 1.10. Comparison 1 Intravenous ibuprofen versus placebo or no drug, Outcome 10 CLD (supplemental oxygen at 28 days of age).
[Analysis 1.11]
Analysis 1.11. Comparison 1 Intravenous ibuprofen versus placebo or no drug, Outcome 11 CLD (supplemental oxygen at 36 weeks PMA).
[Analysis 1.12]
Analysis 1.12. Comparison 1 Intravenous ibuprofen versus placebo or no drug, Outcome 12 Periventricular leukomalacia.
[Analysis 1.13]
Analysis 1.13. Comparison 1 Intravenous ibuprofen versus placebo or no drug, Outcome 13 Mortality.
[Analysis 2.1]
Analysis 2.1. Comparison 2 Oral ibuprofen versus placebo or no drug, Outcome 1 Failure to close a PDA after single or three doses.
[Analysis 3.1]
Analysis 3.1. Comparison 3 Intravenous or oral ibuprofen versus iv or oral indomethacin, Outcome 1 Failure to close a PDA (after single or three doses).
[Analysis 3.2]
Analysis 3.2. Comparison 3 Intravenous or oral ibuprofen versus iv or oral indomethacin, Outcome 2 All cause mortality.
[Analysis 3.3]
Analysis 3.3. Comparison 3 Intravenous or oral ibuprofen versus iv or oral indomethacin, Outcome 3 Neonatal mortality (during first 28/30 days of life).
[Analysis 3.4]
Analysis 3.4. Comparison 3 Intravenous or oral ibuprofen versus iv or oral indomethacin, Outcome 4 Reopening of the ductus arteriosus.
[Analysis 3.5]
Analysis 3.5. Comparison 3 Intravenous or oral ibuprofen versus iv or oral indomethacin, Outcome 5 Need for surgical closure of the PDA.
[Analysis 3.6]
Analysis 3.6. Comparison 3 Intravenous or oral ibuprofen versus iv or oral indomethacin, Outcome 6 Need for re-treatment with indomethacin or ibuprofen to close the PDA.
[Analysis 3.7]
Analysis 3.7. Comparison 3 Intravenous or oral ibuprofen versus iv or oral indomethacin, Outcome 7 Duration of ventilatory support.
[Analysis 3.8]
Analysis 3.8. Comparison 3 Intravenous or oral ibuprofen versus iv or oral indomethacin, Outcome 8 Duration of supplementary oxygen.
[Analysis 3.9]
Analysis 3.9. Comparison 3 Intravenous or oral ibuprofen versus iv or oral indomethacin, Outcome 9 Pulmonary haemorrhage.
[Analysis 3.10]
Analysis 3.10. Comparison 3 Intravenous or oral ibuprofen versus iv or oral indomethacin, Outcome 10 Pulmonary hypertension.
[Analysis 3.11]
Analysis 3.11. Comparison 3 Intravenous or oral ibuprofen versus iv or oral indomethacin, Outcome 11 Chronic lung disease (at 28 days).
[Analysis 3.12]
Analysis 3.12. Comparison 3 Intravenous or oral ibuprofen versus iv or oral indomethacin, Outcome 12 Chronic lung disease (at 36 weeks postmenstrual age).
[Analysis 3.13]
Analysis 3.13. Comparison 3 Intravenous or oral ibuprofen versus iv or oral indomethacin, Outcome 13 Chronic lung disease (age not stated).
[Analysis 3.14]
Analysis 3.14. Comparison 3 Intravenous or oral ibuprofen versus iv or oral indomethacin, Outcome 14 Intraventricular haemorrhage (grades I-IV).
[Analysis 3.15]
Analysis 3.15. Comparison 3 Intravenous or oral ibuprofen versus iv or oral indomethacin, Outcome 15 Intraventricular haemorrhage (grades III-IV).
[Analysis 3.16]
Analysis 3.16. Comparison 3 Intravenous or oral ibuprofen versus iv or oral indomethacin, Outcome 16 Periventricular leukomalacia (cystic).
[Analysis 3.17]
Analysis 3.17. Comparison 3 Intravenous or oral ibuprofen versus iv or oral indomethacin, Outcome 17 Necrotising enterocolitis (any stage).
[Analysis 3.18]
Analysis 3.18. Comparison 3 Intravenous or oral ibuprofen versus iv or oral indomethacin, Outcome 18 Intestinal perforation.
[Analysis 3.19]
Analysis 3.19. Comparison 3 Intravenous or oral ibuprofen versus iv or oral indomethacin, Outcome 19 Gastrointestinal bleed.
[Analysis 3.20]
Analysis 3.20. Comparison 3 Intravenous or oral ibuprofen versus iv or oral indomethacin, Outcome 20 Time to full enteral feeds.
[Analysis 3.21]
Analysis 3.21. Comparison 3 Intravenous or oral ibuprofen versus iv or oral indomethacin, Outcome 21 Time to regain birth weight (days).
[Analysis 3.22]
Analysis 3.22. Comparison 3 Intravenous or oral ibuprofen versus iv or oral indomethacin, Outcome 22 Retinopathy of prematurity.
[Analysis 3.23]
Analysis 3.23. Comparison 3 Intravenous or oral ibuprofen versus iv or oral indomethacin, Outcome 23 Sepsis.
[Analysis 3.24]
Analysis 3.24. Comparison 3 Intravenous or oral ibuprofen versus iv or oral indomethacin, Outcome 24 Decreased urine output (<1 cc/kg/hr).
[Analysis 3.25]
Analysis 3.25. Comparison 3 Intravenous or oral ibuprofen versus iv or oral indomethacin, Outcome 25 Serum/plasma creatinine levels (micromol/L) 72 hours after treatment.
[Analysis 3.26]
Analysis 3.26. Comparison 3 Intravenous or oral ibuprofen versus iv or oral indomethacin, Outcome 26 Increase in serum/plasma creatinine levels (mg/dL) following treatment.
[Analysis 3.27]
Analysis 3.27. Comparison 3 Intravenous or oral ibuprofen versus iv or oral indomethacin, Outcome 27 Duration of hospitalisation.
[Analysis 4.1]
Analysis 4.1. Comparison 4 Oral ibuprofen versus iv or oral indomethacin, Outcome 1 Failure to close a PDA (after three doses).
[Analysis 4.2]
Analysis 4.2. Comparison 4 Oral ibuprofen versus iv or oral indomethacin, Outcome 2 All cause mortality.
[Analysis 4.3]
Analysis 4.3. Comparison 4 Oral ibuprofen versus iv or oral indomethacin, Outcome 3 Neonatal mortality (during first 28/30 days of life).
[Analysis 4.4]
Analysis 4.4. Comparison 4 Oral ibuprofen versus iv or oral indomethacin, Outcome 4 Reopening of the ductus arteriosus.
[Analysis 4.5]
Analysis 4.5. Comparison 4 Oral ibuprofen versus iv or oral indomethacin, Outcome 5 Need for surgical closure of the PDA.
[Analysis 4.6]
Analysis 4.6. Comparison 4 Oral ibuprofen versus iv or oral indomethacin, Outcome 6 Pulmonary haemorrhage.
[Analysis 4.8]
Analysis 4.8. Comparison 4 Oral ibuprofen versus iv or oral indomethacin, Outcome 8 Chronic lung disease (at 28 days).
[Analysis 4.10]
Analysis 4.10. Comparison 4 Oral ibuprofen versus iv or oral indomethacin, Outcome 10 Chronic lung disease (age not stated).
[Analysis 4.11]
Analysis 4.11. Comparison 4 Oral ibuprofen versus iv or oral indomethacin, Outcome 11 Intraventricular haemorrhage (grades I-IV).
[Analysis 4.12]
Analysis 4.12. Comparison 4 Oral ibuprofen versus iv or oral indomethacin, Outcome 12 Intraventricular haemorrhage (grades III-IV).
[Analysis 4.13]
Analysis 4.13. Comparison 4 Oral ibuprofen versus iv or oral indomethacin, Outcome 13 Periventricular leukomalacia (cystic).
[Analysis 4.14]
Analysis 4.14. Comparison 4 Oral ibuprofen versus iv or oral indomethacin, Outcome 14 Necrotising enterocolitis (any stage).
[Analysis 4.15]
Analysis 4.15. Comparison 4 Oral ibuprofen versus iv or oral indomethacin, Outcome 15 Intestinal perforation.
[Analysis 4.16]
Analysis 4.16. Comparison 4 Oral ibuprofen versus iv or oral indomethacin, Outcome 16 Gastrointestinal bleed.
[Analysis 4.17]
Analysis 4.17. Comparison 4 Oral ibuprofen versus iv or oral indomethacin, Outcome 17 Retinopathy of prematurity.
[Analysis 4.18]
Analysis 4.18. Comparison 4 Oral ibuprofen versus iv or oral indomethacin, Outcome 18 Sepsis.
[Analysis 4.19]
Analysis 4.19. Comparison 4 Oral ibuprofen versus iv or oral indomethacin, Outcome 19 Oliguria (< 1 cc/kg/hr).
[Analysis 4.20]
Analysis 4.20. Comparison 4 Oral ibuprofen versus iv or oral indomethacin, Outcome 20 Serum/plasma creatinine levels (micromol/L) 72 hours after treatment.
[Analysis 5.1]
Analysis 5.1. Comparison 5 Oral ibuprofen versus iv ibuprofen, Outcome 1 Failure to close a PDA (after single or three doses).
[Analysis 5.2]
Analysis 5.2. Comparison 5 Oral ibuprofen versus iv ibuprofen, Outcome 2 Mortality (during first 28/30 days of life).
[Analysis 5.3]
Analysis 5.3. Comparison 5 Oral ibuprofen versus iv ibuprofen, Outcome 3 Mortality (during hospital stay).
[Analysis 5.4]
Analysis 5.4. Comparison 5 Oral ibuprofen versus iv ibuprofen, Outcome 4 Mean plasma cystatin-C (mg/L) after treatment.
[Analysis 5.5]
Analysis 5.5. Comparison 5 Oral ibuprofen versus iv ibuprofen, Outcome 5 Need for surgical closure of the ductus.
[Analysis 5.6]
Analysis 5.6. Comparison 5 Oral ibuprofen versus iv ibuprofen, Outcome 6 Duration of ventilatory support.
[Analysis 5.7]
Analysis 5.7. Comparison 5 Oral ibuprofen versus iv ibuprofen, Outcome 7 Duration of hospitalisation (days).
[Analysis 5.8]
Analysis 5.8. Comparison 5 Oral ibuprofen versus iv ibuprofen, Outcome 8 Pneumothorax.
[Analysis 5.9]
Analysis 5.9. Comparison 5 Oral ibuprofen versus iv ibuprofen, Outcome 9 Pulmonary haemorrhage.
[Analysis 5.10]
Analysis 5.10. Comparison 5 Oral ibuprofen versus iv ibuprofen, Outcome 10 Pulmonary hypertension.
[Analysis 5.12]
Analysis 5.12. Comparison 5 Oral ibuprofen versus iv ibuprofen, Outcome 12 Chronic lung disease (at 36 weeks postmenstrual age or at discharge).
[Analysis 5.14]
Analysis 5.14. Comparison 5 Oral ibuprofen versus iv ibuprofen, Outcome 14 Intraventricular haemorrhage (grades I-IV).
[Analysis 5.16]
Analysis 5.16. Comparison 5 Oral ibuprofen versus iv ibuprofen, Outcome 16 Periventricular leukomalacia.
[Analysis 5.17]
Analysis 5.17. Comparison 5 Oral ibuprofen versus iv ibuprofen, Outcome 17 Necrotising enterocolitis (any stage).
[Analysis 5.18]
Analysis 5.18. Comparison 5 Oral ibuprofen versus iv ibuprofen, Outcome 18 Intestinal perforation.
[Analysis 5.19]
Analysis 5.19. Comparison 5 Oral ibuprofen versus iv ibuprofen, Outcome 19 Gastrointestinal bleed.
[Analysis 5.20]
Analysis 5.20. Comparison 5 Oral ibuprofen versus iv ibuprofen, Outcome 20 Sepsis.
[Analysis 5.21]
Analysis 5.21. Comparison 5 Oral ibuprofen versus iv ibuprofen, Outcome 21 Retinopathy of prematurity that required laser treatment.
[Analysis 5.22]
Analysis 5.22. Comparison 5 Oral ibuprofen versus iv ibuprofen, Outcome 22 Serum/plasma creatinine levels (micromol/L) after treatment.
[Analysis 5.23]
Analysis 5.23. Comparison 5 Oral ibuprofen versus iv ibuprofen, Outcome 23 Oliguria (< 1cc/kg/hr).
[Analysis 6.1]
Analysis 6.1. Comparison 6 High dose versus standard dose of ibuprofen, Outcome 1 Failure to close a PDA after three doses of ibuprofen.
[Analysis 6.2]
Analysis 6.2. Comparison 6 High dose versus standard dose of ibuprofen, Outcome 2 Reopening after 2nd course of ibuprofen.
[Analysis 6.3]
Analysis 6.3. Comparison 6 High dose versus standard dose of ibuprofen, Outcome 3 Need for surgical closure.
[Analysis 6.4]
Analysis 6.4. Comparison 6 High dose versus standard dose of ibuprofen, Outcome 4 Death during hospital stay.
[Analysis 6.5]
Analysis 6.5. Comparison 6 High dose versus standard dose of ibuprofen, Outcome 5 Urine output on day 3 (mL/kg/hr).
[Analysis 6.6]
Analysis 6.6. Comparison 6 High dose versus standard dose of ibuprofen, Outcome 6 Oliguria (< 1 mL/kg/hr during 24 hrs).
[Analysis 6.7]
Analysis 6.7. Comparison 6 High dose versus standard dose of ibuprofen, Outcome 7 Intraventricular haemorrhage (all grades).
[Analysis 6.8]
Analysis 6.8. Comparison 6 High dose versus standard dose of ibuprofen, Outcome 8 Intraventricular haemorrhage (grades III-IV).
[Analysis 6.9]
Analysis 6.9. Comparison 6 High dose versus standard dose of ibuprofen, Outcome 9 Periventricular leukomalacia.
[Analysis 6.10]
Analysis 6.10. Comparison 6 High dose versus standard dose of ibuprofen, Outcome 10 Retinopathy of prematurity.
[Analysis 6.11]
Analysis 6.11. Comparison 6 High dose versus standard dose of ibuprofen, Outcome 11 Retinopathy of prematurity (Stage ≥3).
[Analysis 6.12]
Analysis 6.12. Comparison 6 High dose versus standard dose of ibuprofen, Outcome 12 Necrotising enterocolitis.
[Analysis 6.13]
Analysis 6.13. Comparison 6 High dose versus standard dose of ibuprofen, Outcome 13 Chronic lung disease at 36 weeks PMA.
[Analysis 6.14]
Analysis 6.14. Comparison 6 High dose versus standard dose of ibuprofen, Outcome 14 Sepsis.
[Analysis 6.15]
Analysis 6.15. Comparison 6 High dose versus standard dose of ibuprofen, Outcome 15 Hospital stay (days).
[Analysis 7.1]
Analysis 7.1. Comparison 7 Early versus expectant administration of iv ibuprofen, Outcome 1 Days on supplemental oxygen during the first 28 days.
[Analysis 7.2]
Analysis 7.2. Comparison 7 Early versus expectant administration of iv ibuprofen, Outcome 2 Days on supplemental oxygen.
[Analysis 7.3]
Analysis 7.3. Comparison 7 Early versus expectant administration of iv ibuprofen, Outcome 3 Days on mechanical ventilation first 28 days.
[Analysis 7.4]
Analysis 7.4. Comparison 7 Early versus expectant administration of iv ibuprofen, Outcome 4 Days on mechanical ventilation.
[Analysis 7.5]
Analysis 7.5. Comparison 7 Early versus expectant administration of iv ibuprofen, Outcome 5 Chronic lung disease at 36 weeks PMA.
[Analysis 7.6]
Analysis 7.6. Comparison 7 Early versus expectant administration of iv ibuprofen, Outcome 6 Death or chronic lung disease at 36 weeks PMA.
[Analysis 7.7]
Analysis 7.7. Comparison 7 Early versus expectant administration of iv ibuprofen, Outcome 7 Death during hospital stay.
[Analysis 7.8]
Analysis 7.8. Comparison 7 Early versus expectant administration of iv ibuprofen, Outcome 8 Pneumothorax.
[Analysis 7.9]
Analysis 7.9. Comparison 7 Early versus expectant administration of iv ibuprofen, Outcome 9 Intraventricular haemorrhage (grades III & IV).
[Analysis 7.10]
Analysis 7.10. Comparison 7 Early versus expectant administration of iv ibuprofen, Outcome 10 PVL.
[Analysis 7.11]
Analysis 7.11. Comparison 7 Early versus expectant administration of iv ibuprofen, Outcome 11 NEC (requiring surgery).
[Analysis 7.12]
Analysis 7.12. Comparison 7 Early versus expectant administration of iv ibuprofen, Outcome 12 Intestinal perforation.
[Analysis 7.13]
Analysis 7.13. Comparison 7 Early versus expectant administration of iv ibuprofen, Outcome 13 Sepsis.
[Analysis 7.14]
Analysis 7.14. Comparison 7 Early versus expectant administration of iv ibuprofen, Outcome 14 ROP stage ≥ 3.