Administration of indomethacin for the prevention of periventricular-intraventricular hemorrhage in high-risk neonates.

One hundred twenty-two preterm infants were enrolled in a placebo-controlled, double-blind trial using intravenous indomethacin for the prevention of periventricular-intraventricular hemorrhage (PVH-IVH). Before random assignment, data on the infants were stratified according to low-weight (500 to 999 g) or high-weight (1000 to 1500 g) subgroups. Cranial sonography was used to document the absence of PVH-IVH before enrollment and the occurrence of PVH-IVH during the 7-day protocol. Indomethacin, 0.1 mg/kg, or placebo was administered before 12 hours of age and at 24, 48, and 72 hours of age. Five patients receiving indomethacin and six receiving placebo were withdrawn before completion of the study. In the remaining 111 patients, the indomethacin and placebo groups were comparable with respect to gestational ages, maternal complications, Apgar scores, ventilatory requirements, complications of prematurity, and mortality rate. PVH-IVH developed in six of 56 infants who received indomethacin and 11 of 55 infants who received placebo (P = 0.174). Analysis of the individual strata showed that the indomethacin-treated infants in the low-weight subgroup sustained a higher mortality rate (11/17 vs 3/16; P = 0.008) without a reduction in the incidence of PVH-IVH. Infants in the indomethacin-treated high-weight subgroup demonstrated a significantly lower incidence of PVH-IVH (2/39 vs 8/39; P = 0.04), but the frequency of high-grade hemorrhages was comparable for both indomethacin- and placebo-treated groups. In summary, the prophylactic administration of intravenous indomethacin for the prevention of PVH-IVH cannot be recommended for infants less than 1000 g. In preterm infants between 1000 and 1500 g birth weight, indomethacin significantly reduced the incidence of PVH-IVH.

RCT Entities:   Population Interventions Outcomes