Study Reevaluates NSAIDS For PDA in Premature Infants Interview with:

Jonathan Slaughter, MD, MPH Assistant Professor of Pediatrics Center for Perinatal Research Nationwide Children's Hospital/The Ohio State University Columbus, OH 43205

Dr. Jonathan Slaughter

Jonathan Slaughter, MD, MPH
Assistant Professor of Pediatrics
Center for Perinatal Research
Nationwide Children’s Hospital/The Ohio State University
Columbus, OH 43205 What are the main findings?

Response: The ductus arteriosus, a fetal blood vessel that limits blood flow through the lungs, normally closes shortly after birth. However, the ductus often remains open in premature infants, leading to patent ductus arteriosus (PDA). Infants with PDA are more likely to die or develop bronchopulmonary dysplasia (BPD), the major chronic lung disease of preterm infants. Nonsteroidal Anti-inflammatory Drug (NSAID) treatment has been shown to close PDAs in preterm infants and NSAID treatment of PDA is common. However, it has never been shown that PDA closure with NSAIDs leads to decreased mortality or improved long-term respiratory outcomes. NSAID closure of PDA has become increasingly controversial in recent years since NSAID treatment has been associated with acute renal injury. Also, these medications are expensive, with the usual three-dose treatment course costing well over $1000 per patient. Due to these controversies, the likelihood of a preterm infant with PDA being treated with NSAIDs varies by clinician and institution and has decreased over time.
Meta-analyses of randomized trials that investigated NSAID (indomethacin and/or ibuprofen) treatment for PDA closure in preterm infants did not show a benefit. However, they were principally designed only to study whether the ductus itself closed following treatment and not to determine if there was an improvement in mortality risk or in respiratory outcomes following NSAID treatment.
Given the difficulty of conducting randomized trials in preterm infants and the urgent need for practicing clinician’s to know whether treatment of PDA in all preterm infants is beneficial, we used a study design that incorporated the naturally occurring practice variation in NSAID treatment for PDA as a mechanism to reduce the risk of biases that are commonly found in non-randomized investigations. This is based on the premise that if NSAID treatment for PDA in preterm infants is truly effective, we should expect to see improved mortality and respiratory outcomes in instances when clinician preference-based NSAID administration rates are higher. What are the main findings?

Response: When we incorporated naturally occurring variation in NSAID treatment due to clinician preference, we found no significant change in mortality or chronic lung disease (bronchopulmonary dysplasia) in preterm infants born at or prior to 28-weeks of gestation following NSAID treatment. What should readers take away from your report?

Response: We found no evidence that NSAID treatment of all preterm infants with PDA is beneficial in reducing mortality or chronic lung disease. Our findings agree with the available randomized trial evidence and support a conservative approach of not automatically treating PDA in all preterm infants. What recommendations do you have for future research as a result of this study?

Response: Implementation research is needed to determine how clinicians can best incorporate our findings into common clinical practice via quality improvement projects to reduce unnecessary NSAID use.

Studies specifically designed to study preterm infants with PDA who are deemed to be at higher mortality and/or respiratory morbidity risk, based on their clinical presentation and/or PDA physiology, are also needed. Although NSAID treatment of all preterm infants with PDA does not seem effective in reducing mortality or chronic lung disease (BPD), NSAID treatment of specific higher-risk populations of infants with PDA may be effective.

It is known that NSAID administration in older patients is associated with a higher risk of kidney injury and other adverse effects. Future studies specifically designed to assess the safety of NSAID (indomethacin and ibuprofen) administration in preterm infants, and the effects of treatment on long-term renal development and function, are needed. Thank you for your contribution to the community.


Slaughter JL, Reagan PB, Newman TB, Klebanoff MA. Comparative Effectiveness of Nonsteroidal Anti-inflammatory Drug Treatment vs No Treatment for Patent Ductus Arteriosus in Preterm Infants. JAMA Pediatr. Published online January 03, 2017e164354. doi:10.1001/jamapediatrics.2016.4354

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Last Updated on January 5, 2017 by Marie Benz MD FAAD