Author Interviews, JAMA, Kidney Disease, Pediatrics / 05.01.2017
Study Reevaluates NSAIDS For PDA in Premature Infants
MedicalResearch.com 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
MedicalResearch.com: 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.
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