Ibuprofen for the treatment of patent ductus arteriosus in preterm or low birth weight (or both) infants

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 adverse effects. To determine the effectiveness and safety of ibuprofen compared with indomethacin, other cyclo-oxygenase inhibitor, placebo or no intervention for closing a patent ductus arteriosus in preterm, low birth weight, or preterm and low birth weight infants. We searched The Cochrane Library, MEDLINE, EMBASE, Clincialtrials.gov, Controlled-trials.com, and www.abstracts2view.com/pas in May 2014. Randomised or quasi-randomised controlled trials of ibuprofen for the treatment of a PDA in newborn infants. Data collection and analysis conformed to the methods of the Cochrane Neonatal Review Group. We included 33 studies enrolling 2190 infants.Two studies compared intravenous (iv) ibuprofen versus placebo (270 infants). In one study (134 infants) ibuprofen reduced the incidence of failure to close a PDA (risk ratio (RR) 0.71, 95% confidence interval (CI) 0.51 to 0.99; risk difference (RD) -0.18, 95% CI -0.35 to -0.01; number needed to treat for an additional beneficial outcome (NNTB) 6, 95% CI 3 to 100). In one study (136 infants), ibuprofen reduced the composite outcome of infant mortality, infants who dropped out, or infants who required rescue treatment (RR 0.58, 95% CI 0.38 to 0.89; RD -0.22, 95% CI -0.38 to -0.06; NNTB 5, 95% CI 3 to 17). One study (64 infants) compared oral ibuprofen with placebo and noted a significant reduction in failure 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).Twenty-one studies (1102 infants) reported failure rates for PDA closure with ibuprofen (oral or iv) compared with indomethacin (oral or iv). There was no significant difference between the groups (typical RR 1.00, 95% CI 0.84 to 1.20; I(2) = 0%; typical RD 0.00, 95% CI -0.05 to 0.05; I(2) = 0%). The risk of developing necrotising enterocolitis (NEC) was reduced for ibuprofen (16 studies, 948 infants; typical RR 0.64, 95% CI 0.45 to 0.93; typical RD -0.05, 95% CI -0.08 to -0.01; NNTB 20, 95% CI 13 to 100; I(2) = 0% for both RR and RD). The duration of ventilatory support was reduced with ibuprofen (oral or iv) compared with iv or oral indomethacin (six studies, 471 infants; mean difference (MD) -2.4 days, 95% CI -3.7 to -1.0; I(2) = 19%).Eight studies (272 infants) reported on