Long-term effects of indomethacin prophylaxis in extremely-low-birth-weight infants

Background: The prophylactic administration of indomethacin reduces the fre quency of patent ductus arteriosus and severe intraventricular hemorrhage i n very-low-birth-weight infants (those with birth weights below 1500 g). Wh ether prophylaxis with indomethacin confers any long-term benefits that out weigh the risks of drug-induced reductions in renal, intestinal, and cerebr al blood flow is not known. Methods: Soon after they were born, we randomly assigned 1202 infants with birth weights of 500 to 999 g (extremely low birth weight) to receive eithe r indomethacin (0.1 mg per kilogram of body weight) or placebo intravenousl y once daily for three days. The primary outcome was a composite of death, cerebral palsy, cognitive delay, deafness, and blindness at a corrected age of 18 months. Secondary long-term outcomes were hydrocephalus necessitatin g the placement of a shunt, seizure disorder, and microcephaly within the s ame time frame. Secondary short-term outcomes were patent ductus arteriosus , pulmonary hemorrhage, chronic lung disease, ultrasonographic evidence of intracranial abnormalities, necrotizing enterocolitis, and retinopathy. Results: Of the 574 infants with data on the primary outcome who were assig ned to prophylaxis with indomethacin, 271 (47 percent) died or survived wit h impairments, as compared with 261 of the 569 infants (46 percent) assigne d to placebo (odds ratio, 1.1; 95 percent confidence interval, 0.8 to 1.4; P=0.61). Indomethacin reduced the incidence of patent ductus arteriosus (24 percent, vs. 50 percent in the placebo group; odds ratio, 0.3; P<0.001) an d of severe periventricular and intraventricular hemorrhage (9 percent, vs. 13 percent in the placebo group; odds ratio, 0.6; P=0.02). No other outcom es were altered by the prophylactic administration of indomethacin. Conclusions: In extremely-low-birth-weight infants, prophylaxis with indome thacin does not improve the rate of survival without neurosensory impairmen t at 18 months, despite the fact that it reduces the frequency of patent du ctus arteriosus and severe periventricular and intraventricular hemorrhage. (N Engl J Med 2001;344:1966-72.) Copyright (C) 2001 Massachusetts Medical Society.