Arne Ohlsson1, Rajneesh Walia, Sachin S Shah. 1. Departments of Paediatrics, Obstetrics and Gynaecology and Health Policy, Management and Evaluation, University of Toronto, 600 University Avenue, Toronto, Ontario, Canada, M5G 1X5.
Abstract
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 effectiveness and safety of ibuprofen compared to placebo or no intervention for closing a PDA in preterm and/or low birth weight infants. To determine the effectiveness and safety of ibuprofen compared to other cyclo-oxygenase inhibitors for closing a PDA in preterm and/or low birth weight infants. SEARCH STRATEGY: MEDLINE, EMBASE, The Cochrane Library, the reference lists of identified studies, meta-analyses and personal files were searched in December 2009. SELECTION CRITERIA: Randomized or quasi-randomized 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 studies are included in this review (6 studies added in this update). One study (n = 136) compared ibuprofen to placebo. Ibuprofen reduced the composite outcome of infant deaths, infants who dropped out or required rescue treatment [RR 0.58 (95% CI 0.38, 0.89); RD -0.22 (95% CI -0.38, -06); NNTB 5 (95% CI 3,17)]. Failure rates for PDA closure with ibuprofen compared to indomethacin was reported in 19 studies (n = 956 infants). There was no statistically significant difference between the groups [typical RR 0.94 (95% CI 0.76, 1.17)]; typical RD -0.02 (95% CI -0.07, 0.04); I(2) = 0%]. The risk of developing necrotizing enterocolitis (NEC) was reduced for ibuprofen [15 studies (n = 865); typical RR 0.68 (95% CI 0.47, 0.99); typical RD -0.04 (95% CI -0.08, -0.00; (p = 0.04); NNTB 25 (95% CI 13, infinity); I(2) = 0%]. There is less evidence of transient renal insufficiency in infants who receive ibuprofen compared to indomethacin. No other important differences were noted for common neonatal morbidities. Oro-gastric administration of ibuprofen appears as effective as i.v. administration. AUTHORS' CONCLUSIONS: Ibuprofen is effective in closing a PDA. 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 noted in this update, ibuprofen currently appears to be the drug of choice. Studies are needed to evaluate the effect of ibuprofen compared to indomethacin treatment on longer term outcomes in infants with PDA.
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 effectiveness and safety of ibuprofen compared to placebo or no intervention for closing a PDA in preterm and/or low birth weight infants. To determine the effectiveness and safety of ibuprofen compared to other cyclo-oxygenase inhibitors for closing a PDA in preterm and/or low birth weight infants. SEARCH STRATEGY: MEDLINE, EMBASE, The Cochrane Library, the reference lists of identified studies, meta-analyses and personal files were searched in December 2009. SELECTION CRITERIA: Randomized or quasi-randomized 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 studies are included in this review (6 studies added in this update). One study (n = 136) compared ibuprofen to placebo. Ibuprofen reduced the composite outcome of infant deaths, infants who dropped out or required rescue treatment [RR 0.58 (95% CI 0.38, 0.89); RD -0.22 (95% CI -0.38, -06); NNTB 5 (95% CI 3,17)]. Failure rates for PDA closure with ibuprofen compared to indomethacin was reported in 19 studies (n = 956 infants). There was no statistically significant difference between the groups [typical RR 0.94 (95% CI 0.76, 1.17)]; typical RD -0.02 (95% CI -0.07, 0.04); I(2) = 0%]. The risk of developing necrotizing enterocolitis (NEC) was reduced for ibuprofen [15 studies (n = 865); typical RR 0.68 (95% CI 0.47, 0.99); typical RD -0.04 (95% CI -0.08, -0.00; (p = 0.04); NNTB 25 (95% CI 13, infinity); I(2) = 0%]. There is less evidence of transient renal insufficiency in infants who receive ibuprofen compared to indomethacin. No other important differences were noted for common neonatal morbidities. Oro-gastric administration of ibuprofen appears as effective as i.v. administration. AUTHORS' CONCLUSIONS:Ibuprofen is effective in closing a PDA. 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 noted in this update, ibuprofen currently appears to be the drug of choice. Studies are needed to evaluate the effect of ibuprofen compared to indomethacin treatment on longer term outcomes in infants with PDA.