Prophylactic Indomethacin vs. Ibuprofen for Patent Ductus Arteriosus in Preterm Infants: Renal and Intestinal Safety Comparison

Abstract

Introduction: Prophylactic cyclooxygenase inhibitors (indomethacin, ibuprofen) are used to close patent ductus arteriosus (PDA) in preterm infants. However, both cause renal and mesenteric hypoperfusion. Comparative safety profiles are debated.

Methods: Systematic review and network meta-analysis of RCTs comparing prophylactic intravenous indomethacin, ibuprofen, or placebo in preterm infants <32 weeks. Primary safety outcomes: acute kidney injury (AKI, defined as serum creatinine rise >0.3 mg/dL or oliguria), necrotizing enterocolitis (NEC) or spontaneous intestinal perforation (SIP). Medline, Embase, Cochrane Library searched.

Results: Eighteen RCTs (n=3,210 infants) were included. Compared to placebo: ibuprofen increased AKI risk (RR 1.38, 95% CI 1.09–1.75); indomethacin increased AKI risk more (RR 1.89, 95% CI 1.46–2.45). For SIP/NEC, indomethacin significantly increased risk (RR 1.72, 95% CI 1.24–2.38) while ibuprofen did not (RR 1.14, 0.77–1.68). Head-to-head: ibuprofen had lower AKI (RR 0.73 vs. indomethacin) and lower SIP/NEC (RR 0.66). PDA closure rates were similar (78% ibuprofen, 81% indomethacin, p=0.34).

Discussion: Ibuprofen has a superior renal and intestinal safety profile compared to indomethacin for prophylactic PDA closure, with equivalent efficacy. Indomethacin’s greater vasoconstrictive effect on mesenteric vessels likely explains higher NEC/SIP. Limitation: most studies excluded infants with baseline renal dysfunction.

Conclusions: When prophylactic PDA closure is indicated (e.g., in infants <26 weeks), ibuprofen is preferred over indomethacin due to reduced risk of AKI and intestinal injury. However, expectant management without prophylaxis is increasingly favored.