Prophylactic Ibuprofen for the Prevention of Intraventricular Hemorrhage Among Preterm Infants: A Multicenter, Randomized Study

Abstract

Objective. Ibuprofen enhances cerebral blood flow autoregulation and was shown to protect neurologic functions after oxidative stresses in an animal model. For these reasons, we hypothesized that the prophylactic use of ibuprofen would reduce the occurrence of intraventricular hemorrhage (IVH) and its worsening toward grades 2 to 4 among preterm infants. To confirm this hypothesis, we planned the present prospective study. Methods. This was a double-blind, randomized, controlled trial in which preterm infants with gestational ages of <28 weeks received ibuprofen or placebo within the first 6 hours of life. The infants were assigned randomly, at 7 neonatal care units, to receive ibuprofen (10 mg/kg, followed by 5 mg/kg after 24 and 48 hours) or placebo. Serial echoencephalography was performed 24 and 48 hours after the initial cerebral ultrasound study, on postnatal days 7, 15, and 30, and at 40 weeks' postconceptional age. Grade 1 IVH or no IVH was considered a successful outcome, whereas grade 2 to 4 IVH represented failure. The rates of ductal closure, side effects, and complications were recorded. Results. We studied 155 infants. Grade 2 to 4 IVH developed for 16% of the ibuprofen-treated infants and 13% of the infants in the placebo group. The occurrence of patent ductus arteriosus was less frequent only on day 3 of life in the ibuprofen group. There were no significant differences with respect to other complications or adverse effects. Conclusions. Our study demonstrated that prophylactic ibuprofen is ineffective in preventing grade 2 to 4 IVH and that its use for this indication cannot be recommended.