Prevention and 18-Month Outcomes of Serious Pulmonary Hemorrhage in Extremely Low Birth Weight Infants: Results From the Trial of Indomethacin Prophylaxis in Preterms

OBJECTIVES: A patent ductus arteriosus is a risk factor for pulmonary hemorrhage; however, despite halving the incidence of patent ductus arteriosus, indomethacin prophylaxis did not reduce the rate of pulmonary hemorrhage in the Trial of Indomethacin Prophylaxis in Preterms. Inclusion of mild bleeds after trauma to the upper airways may have masked a beneficial drug effect. Using the Trial of Indomethacin Prophylaxis in Preterms database, we studied the effect of prophylactic indomethacin on the prevention of serious hemorrhages in extremely low birth weight infants. We also compared the 18-month outcomes of infants with and without a serious pulmonary bleed. METHODS: Pulmonary hemorrhage was classified as serious when it was treated with increased ventilator support, a higher concentration of oxygen, or transfusion of blood products. The cumulative risk for serious pulmonary hemorrhage was estimated for the first week of life and for the entire NICU stay. Poor outcome at a corrected age of 18 months was death or survival with cerebral palsy, cognitive delay, blindness, and/or deafness. RESULTS: A total of 123 (10.2%) of 1202 infants developed a serious pulmonary hemorrhage. During week 1, prophylactic indomethacin reduced the risk for serious pulmonary hemorrhage by 35%; however, during the entire NICU stay, the risk for such hemorrhages was decreased by only 23%. A reduced risk for patent ductus arteriosus explained 80% of the beneficial effect of prophylactic indomethacin on serious pulmonary bleeds. The risks for death or for survival with neurosensory impairment were doubled after a serious pulmonary hemorrhage. CONCLUSIONS: Extremely low birth weight infants with serious pulmonary hemorrhage have an increased risk for poor long-term outcome. Prophylactic indomethacin reduces the rate of early serious pulmonary hemorrhage, mainly through its action on patent ductus arteriosus. Prophylactic indomethacin is less effective in preventing serious pulmonary hemorrhages that occur after the first week of life.