Columbus, OH - January 2017
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been established as effective in closing patent ductus arteriosus (PDA), and PDA is associated with increased mortality and poorer respiratory outcomes in babies born preterm. So specialists have often used NSAIDs to treat infants with PDA – in the absence of robust research demonstrating the treatment actually has a positive effect on outcomes.
A recent study in JAMA Pediatrics, led by physician-researchers at Nationwide Children’s Hospital, in fact found no changes in the odds of mortality or moderate/severe bronchopulmonary dysplasia (BPD) in infants born very preterm who received NSAIDs for PDA.
“For decades we have assumed that we should treat to close the ductus in these babies,” says Jonathan L. Slaughter, MD, MPH, a neonatologist at Nationwide Children’s and lead author of the study. “No one has really powered trials to look at long term outcomes, though, and long-term outcomes are why we give these infants NSAIDs in the first place.”
A few limited studies have led Nationwide Children’s and some other institutions to curtail NSAID treatment for PDA in preterm infants, says Dr. Slaughter, who is also a principal investigator in the Center for Perinatal Research at The Research Institute at Nationwide Children’s. This research supports those who are administering the drugs less often.
“This study is not saying that no baby with PDA should be treated with NSAIDs,” Dr. Slaughter says. “But in the future, research is needed to determine how severe a patent ductus must be before it should be treated. Perhaps the number of babies requiring treatment are fewer than current national practice.”
The authors examined data drawn from the Pediatric Health Information System and used 12,018 infants born ≤28 weeks gestational age as the study cohort. Overall, 32 percent were treated with indomethacin or ibuprofen for PDA. The annual treatment rate decreased from 40.6 percent in 2005 to 24.1 percent in 2013.
An instrumental variable analysis was performed to reduce unmeasured confounders in the dataset, essentially mimicking a randomized trial, according to Dr. Slaughter. The authors had previously conducted a survey of hospitals in the Pediatric Health Information System and found that provider preference rather than condition severity was likely to guide the decision to use NSAIDs. That practice variation was included as an element of the analysis.
Odds of mortality and moderate/severe BPD were not improved with increased use of NSAIDs in the cohort. Combined with other concerns, the study may lead some providers to rethink their NSAID guidelines for PDA.
“There are potential side effects, and there have not been many safety studies on NSAID use in newborns,” says Dr. Slaughter. “These drugs can also be expensive in neonatal formulations, at well over $1000 per three-dose treatment course, so institutions may be spending a lot of money on treatment that is ultimately not very helpful.”
This study has been supported in part by Award Number Grant UL1TR001070 from the National Center For Advancing Translational Sciences.
Slaughter JL, Reagan PB, Newman TB, Klebanoff MA. Comparative effectiveness of nonsteroidal anti-inflammatory drug treatment versus no treatment for patent ductus arteriosus in preterm infants. JAMA Pediatrics. 2017 Jan 3. [Epub ahead of print]
Slaughter JL, Reagan PB, Bapat RV, Newman TB, Klebanoff MA. Nonsteroidal anti-inflammatory administration and patent ductus arteriosus ligation, a survey of practice preferences at US children's hospitals. European Journal of Pediatrics. 2016 Jun;175(6):775-83.