NSAIDs do not improve mortality in preterm infants with patent ductus arteriosus
Nonsteroidal anti-inflammatory drug (NSAID) treatment for patent ductus arteriosus (PDA) in preterm infants did not reduce the odds of mortality or bronchopulmonary dysplasia (BPD), a recent US study found.
Instrumental variable analysis did not reveal any association between NSAID treatment and the odds of mortality or BPD (odds ratio [OR], 0.94, 95 percent CI, 0.70–1.25; p=0.69), mortality (OR, 0.73, 95 percent CI, 0.43–1.13; p=0.18), or BPD (OR, 1.01, 95 percent CI, 0.73–1.45; p=0.94). [JAMA Pediatr 2017;doi:10.1001/jamapediatrics.2016.4354]
Researchers gathered data on 12,018 infants born at 28 gestational weeks or younger from the PHIS* database (Children’s Hospital Association, Shawnee Mission, Kansas, US).
Of these, 32 percent received NSAID treatment for PDA (7 percent on ibuprofen, 27 percent on indomethacin). The infants either received an initial dose of ibuprofen or indomethacin within the initial 28 postnatal days (4 or more days). Infants who received a prophylactic indomethacin dose to prevent intraventricular haemorrhage (daily dose from birth date for 3 consecutive days) were also qualified. Infants who received NSAID doses beyond 28 postnatal days were excluded.
PDA is present in infants at birth between 25 and 28 weeks gestation and is predominant in extremely preterm infants, with 35 percent closing within 1 week. However, nonclosure is associated with increased mortality and worsened respiratory outcomes including BPD. [Semin Perinatol 2012;36:123-129; Pediatrics 2009;123:e138-e144]
Although previous studies have demonstrated the efficacy of NSAIDs in PDA treatment, their ability to improve mortality or prevent BPD remain unclear. [Cochrane Database Syst Rev (2): CD003745, 2003; Cochrane Database Syst Rev (2):CD003481, 2015; Arch Dis Child Fetal Neonatal Ed 2007;92:F498-F502]
“Our findings … support a conservative approach to PDA management … Although NSAID treatment of all infants with PDA does not appear beneficial, our findings do not imply that some infants with certain risk factors may not benefit from PDA closure,” said the researchers.