Early versus Late Indomethacin Treatment for Patent Ductus Arteriosus in Premature Infants with Respiratory Distress Syndrome. Van Obermeire B, Van de Broek H, Van Laer P, et al. J Pediatr Feb 2001; 138:205-11).

127 neonates (EGA 26-31 weeks) receiving ventilatory assistance and with PDA by echocardiography were randomly assigned in a prospective multicenter trial to either early (day 3, n = 64) or late (day 7, n = 63) IV indomethacin treatment (3 X 00.2 mg/kg q12h). The PDA closure rate was higher in the early treatment group at both 6 (73% vs 44%, p = 0.0008) and 9 days of age (91% vs 78%, p = 0.047). There were no significant difference between groups in the rates of PDA ligation. Urine output was significantly lower (p < 0.0001), serum creatinine level was higher (p = 0.016), and more indomethacin courses were administered in the early treatment group (70 vs 26). Respiratory support, number of deaths, and IVH were similar in both groups. On the whole, major adverse events (death, NEC, small bowel perforations, extension of hemorrhage or cystic PVL) occurred more frequently in the early treatment group (p = 0.017).