Objective: Compare the use of nonsteroidal anti-inflammatory drugs (NSAIDs) with placebo/expectant management in preterm infants at 28 weeks or less gestational age with a large Patent Ductus (PDA).

Methods: A meta-analysis of RCTs following PRISMA guidelines comparing the use of NSAIDs with placebo/expectant management in extremely preterm infants with a large PDA.

Results: There were no significant differences between the NSAIDs and placebo/expectant groups for all-cause mortality (RR 1.27; 95% CI 0.97-1.65; p = 0.081). However, the ibuprofen subgroup showed a significant difference in all-cause mortality (RR 1.36; 95% CI 1.03-1.80; p = 0.03) favoring the placebo/expectant group.

Conclusions: In extremely preterm infants with a large PDA on ultrasound, early treatment with NSAIDs provides no additional clinical benefit compared to placebo/expectant treatment. Ibuprofen was associated with an increased risk ratio for all-cause mortality in the subgroup analysis.