Acetaminophen versus indomethacin for patent ductus arteriosus management in premature infants: systematic review and meta-analysis of randomized controlled trials

Objectives Acetaminophen has gained interest in the neonatal community for its use in the management of hemodynamically significant patent ductus arteriosus (HsPDA) in preterm infants. We conducted a systematic review of randomized controlled trials (RCTs) comparing the efficacy and safety of acetaminophen with indomethacin for the management of HsPDA in preterm infants. Methods We searched PROSPERO, OVID Medline, OVID EMBASE, Wiley Cochrane Library (CDSR and Central), EBSCO CINAHL, and SCOPUS from inception to June 15, 2021. Bibliographies of identified studies were searched for additional references. Data were analyzed with Review Manager (RevMan) Version 5.3. Results Four RCTs were identified, enrolling a total of 380 subjects. There was no difference between the interventions for the outcome of PDA closure after one course (RR 1.04 [95% CIs: 0.84, 1.29], P-value 0.70) or after two courses of treatment (RR 1.01 [95% CIs: 0.92, 1.12], P-value 0.77); and for the outcome of PDA ligation (RR 1.56 [95% CIs: 0.48, 5.12], P-value 0.46). However, patients who received acetaminophen had lower rates of necrotizing enterocolitis (RR 0.37 [95% CIs: 0.14, 0.95], P-value 0.04). There were no significant differences noted in the other clinical outcomes, that is, intraventricular hemorrhage, bronchopulmonary dysplasia, retinopathy of prematurity requiring treatment, and death. Two studies noted significant post-treatment elevation of serum creatinine and blood urea with indomethacin, as compared to none with acetaminophen use. Conclusions Acetaminophen has comparable efficacy to indomethacin for the outcome of HsPDA closure, with a better safety profile, that is, lesser rates of necrotizing enterocolitis and post-treatment azotemia noted with its use.