DOUBLE-BLIND, RANDOMIZED TRIAL OF ONE VERSUS 3 PROPHYLACTIC DOSES OF SYNTHETIC SURFACTANT IN 826 NEONATES WEIGHING 700 TO 1100 GRAMS - EFFECTS ON MORTALITY-RATE

At 33 hospitals in the United States, a double-blind, randomized clini cal trial was performed to compare one versus three prophylactic doses of synthetic surfactant in 700 to 1100 gm inborn infants. All 826 inf ants received an initial prophylactic dose of surfactant within 30 min utes of birth. Subsequently 410 infants received two doses of placebo (air) 12 and 24 hours later, and 416 infants received two additional d oses of surfactant, By the age of 28 days, 70 infants who received one dose of surfactant and 40 infants who received three doses were dead, a 43% relative reduction in the mortality rate (30 fewer deaths; p = 0.002). By the age of 1 year after term, 87 infants who received one d ose and 62 infants who received three doses were dead: a 29% relative reduction in the mortality rate (25 fewer deaths; p = 0.027). Infants who received three doses of surfactant required significantly less oxy gen and less mean airway pressure for the first week of life. Necrotiz ing enterocolitis (9 vs 25 infants; p = 0.005), and use of high-freque ncy ventilation (13 vs 26 infants; p = 0.037); pancuronium (43 vs 62 i nfants; p = 0.045); and leukocyte transfusions (0 vs 4 infants; p = 0. 042) were less frequent in the three-dose group, but air leak, broncho pulmonary dysplasia, intraventricular hemorrhage, patent ductus arteri osus, pulmonary hemorrhage, and infections were not different. These r esults indicate that physiologic findings, mortality rates, and probab ly morbidity rates are improved by two additional prophylactic doses o f synthetic surfactant.