Ron Clyman and a multicenter group have just published this DAFFII trial. Which is a rather tortuous light-hearted acronym for Ductus Arteriosus Feed or Fast with Indomethcain or Ibuprofen. (Clyman R, Wickremasinghe A, Jhaveri N, Hassinger DC, Attridge JT, Sanocka U, Polin R, Gillam-Krakauer M, Reese J, Mammel M et al: Enteral feeding during indomethacin and ibuprofen treatment of a patent ductus arteriosus. The Journal of pediatrics 2013, 163(2):406-411.)
Despite the acronym this was a rather important trial. No-one knows what to do with enteral feeding when you treat a PDA with either ibuprofen or indomethacin. As a result there is a lot of variability in practice. These authors randomized 177 babies (400 to 1250g birth weight) who had started their enteral feeds (less than 60 mL/kg/d) to either go onto trophic feeds (15 mL/kg/d) and then advance according to a standard regime, or to be placed nil by mouth during the drug administration, before going back on the standard regime. They terminated the study early because of enrollment difficulties, partly due to people treating babies for the PDA later in their life than they used to, and due to the drugs not being available at different times.
The babies who continued trophic feeds during the PDA treatment reached their goal feeds (which the study decided was 120 mL/kg/d) about 3 days faster. There were no adverse effects of the continued feeding regime. Of interest in the results, there was a lot of NEC 13% in the fasted group, 10% in the trophic group, despite a high rate of breast milk feeding, 84%, and a lot of infections, 45% in each group. They also gave the first feeds fairly late, averaging 3.5 to 5 days of age when the first feed was given.
I think the next thing we need to study is to just keep feeding, and keep advancing the feeds during PDA treatment. My own practice has been to stop advancing the feeds, if we are still in the feed advancement stage, but not to reduce them, and then to restart the feed advancement after the indo or ibuprofen is stopped. Like many of us we are treating few PDAs in early life now, so many of the babies are well advanced on their feeds, or at full feeds when we give the ibuprofen.
It would be great to have good data on what we should really do.
The numerous small case series of using acetaminophen (paracetamol for non-North Americans) for PDA closure are also intriguing, I don’t know if it really works, but it might be safer for the GI tract if it does. Allegaert K, Anderson B, Simons S, van Overmeire B: Paracetamol to induce ductus arteriosus closure: Is it valid? Archives of Disease in Childhood 2013, 98(6):462-466.