PDA is a common complication for very preterm (premature) or very small babies. PDA is an open vessel that channels blood from the lungs to the body. 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. Indomethacin is successful in causing PDA closure, but can cause serious adverse effects. Another option is the drug ibuprofen, which can be given to try and prevent PDA. This updated review of trials found that ibuprofen can prevent PDA, but does not confer any other short-term or long-term benefits.
Prophylactic use of ibuprofen decreased the incidence of PDA, decreased the need for rescue treatment with cyclo-oxygenase inhibitors and decreased the need for surgical closure. In the control group, the PDA closed spontaneously by day three in 58% of the neonates. Prophylactic treatment exposes many infants to a drug that has concerning renal and gastrointestinal side effects without conferring any important short-term benefits and is not recommended. Until long-term follow-up results are published from the trials included in this updated review, no further trials of prophylactic ibuprofen are recommended.
Patent ductus arteriosus (PDA) complicates the clinical course of preterm infants and increases the risk of adverse outcomes. Indomethacin has been the standard treatment to close a PDA but is associated with renal, gastrointestinal and cerebral side-effects. Ibuprofen has less effect on blood flow velocity to important organs.
To determine the effectiveness and safety of prophylactic ibuprofen compared to placebo/no intervention in the prevention of PDA in preterm infants.
Randomized controlled trials of prophylactic ibuprofen were identified by searching in The Cochrane Library, MEDLINE, CINAHL, EMBASE and trials registries in December 2010.
Randomized or quasi-randomised controlled trials comparing ibuprofen with placebo/no intervention or other cyclo-oxygenase inhibitor drugs to prevent PDA in preterm and/or low birth weight infants.
Outcomes data including presence of PDA on day three, need for surgical ligation or rescue treatment with cyclo-oxygenase inhibitors, mortality, intraventricular haemorrhage (IVH), renal, pulmonary and gastrointestinal complications were extracted. Meta-analyses were performed and treatment estimates are reported as typical weighted mean difference, relative risk (RR), risk difference (RD) and, if statistically significant, number needed to treat to benefit (NNT) or number needed to treat to harm (NNH) along with their 95% confidence intervals (CI).
In this update, seven studies (n = 931) comparing prophylactic ibuprofen with placebo/no intervention are included. Ibuprofen decreased the incidence of PDA on day three [typical RR 0.36 (95% CI 0.29 to 0.46); typical RD -0.27 (95% CI -0.32 to -0.21); NNT 4 (95% CI 3 to 5)], decreased the need for rescue treatment with cyclo-oxygenase inhibitors and decreased the need for surgical ligation. Results from two studies administering oral ibuprofen had similar results, but showed an increased risk of gastrointestinal bleeding (NNH 4, 95% CI 2 to 17). In the control group the spontaneous closure rate was 58% by day three. Ibuprofen negatively affects renal function. No significant differences in mortality, IVH, chronic lung disease were found.