Oral Ibuprofen and the patent ductus arteriosus: a new approach to an old problem.

Patent ductus arteriosus (PDA) is present in up to 75% of infants born before 28 weeks gestation, and issues concerning PDA remain a popular topic in neonatology. The large range of articles addressing the assessment and treatment of PDA demonstrates the continuing uncertainty regarding the best way to manage an infant with this complication of prematurity. PDA is associated with many of the adverse outcomes of prematurity; however, there are conflicting results on the benefits of PDA closure from the many randomised and observational studies targeting PDA treatment. Consequently, there are ongoing questions as to when to treat, what to treat, and how to treat. Complicating factors, such as efficacy, dosage issues, risk of side effects, and the large variation in cost of potential treatments are becoming increasingly important, as neonatologists try to optimize available therapies. Neonatology has a track record of introducing medications before the pharmacokinetics in our population are properly understood. Enteral or intravenous indomethacin was the mainstay of PDA treatment for many years, ever since its use was first described in 1976. More recently, ibuprofen, initially as an intravenous infusion, has been utilized and found to be of similar efficacy as intravenous indomethacin. There are, however, indications that the appropriate dose to maintain therapeutic ibuprofen levels is not being achieved with intravenous dosing, resulting in increased treatment failure rates. Oral medication, which is simple to administer and effective, with minimal side effects, would be likely to change the balance in favour of treatment in many preterm infants. In this issue of the Journal, Yang et al. describe their experience with the use of oral ibuprofen versus intravenous indomethacin in a group of extremely low birth weight infants. In this retrospective cohort study, oral ibuprofen syrup (10 mg/kg initial dose, followed by two doses of 5 mg/kg at 24-hour intervals) was found to be as efficacious as intravenous indomethacin. The closure rate on initial treatment was 81.8% for oral ibuprofen versus 88.5% for intravenous indomethacin (p = 0.40). Importantly, there were no differences in side effects or complications between the two approaches. These were small infants, all under 1,000 g, and treated on average at 5 days of age. Other studies have confirmed the high closure rates and favourable safety profile of oral ibuprofen. Most recently, Erdeve et al. performed a randomised controlled trial of oral versus intravenous ibuprofen in 80 preterm infants, and found a higher initial closure rate with oral ibuprofen, though there was a higher re-opening rate in infants who received this treatment. Interestingly, there was also a reduction in the incidence of chronic lung disease in the orally treated group. Other studies have