What is the Most Efficacious Pharmacological Therapy for Patent Ductus Arteriosus Closure in Premature Infants?

We read with great interest the systematic review and meta-analysis by Mitra et-al published recently in JAMA. (1) This metanalysis attempts to identify the pharmacological intervention which results in the best closure rates of a patent ductus arteriosus (PDA) in infants less than 37 weeks gestation. The group carried out a detailed review of 67 randomised controlled trials (RCTs), published between 1980 and 2017, including 4802 patients examining fourteen variations of indomethacin, ibuprofen, or acetaminophen (paracetamol) as treatment modalities for a PDA. The following primary outcomes were assessed: PDA closure within one week of administration of the first dose, need for repeat pharmacotherapy or surgical ligation. Adverse outcomes were defined as necrotising enterocolitis, neurological events, bronchopulmonary dysplasia, oliguria and neonatal mortality. This paper has an important message incorporating new information that is not in keeping with current clinical practice: a high oral dose of ibuprofen was associated with a greater rate of closure of a PDA at one week when compared to standard dose intravenous (IV) ibuprofen, IV indomethacin and oral acetaminophen. There were no differences between the no treatment/placebo group or treatment groups in mortality, necrotising enterocolitis or intraventricular haemorrhage.