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Abstract. Background and objective. Surfactant replacement is a powerful therapy for newborns with respiratory distress syndrome, but limited observations suggest that alterations of cerebral blood flow can accompany the use of several available surfactants. An early European multicenter controlled study with beractant demonstrated an increased rate of intracranial hemorrhage in treated patients. Nine additional controlled studies were subsequently performed and included follow-up evaluations through 2 years adjusted age. This clinical experience provided a database of approximately 1700 infants to examine retrospectively for any relationship between surfactant therapy and intracranial hemorrhage. Methods. Cumulative incidence rates, hazard ratios, and 95% confidence intervals for intracranial hemorrhage were computed for each study and for appropriately pooled studies of similar design. Where an association between surfactant and the risk of intracranial hemorrhage was found, additional analyses were performed to attempt to identify intermediate physiologic events that might link administration of surfactant to the occurrence of intracranial hemorrhage. These analyses were guided by literature reports of hemodynamic changes observed in association with surfactant therapy. Results. During the controlled studies with beractant, treated newborns of 600 to 750 g birth weight were at higher risk for grades I and II intracranial hemorrhage than control newborns. There was no increased risk for grades III and IV hemorrhage among these newborns, nor was there increased risk of hemorrhage among any other patient groups. This finding did not result in increased morbidity for the affected patients; at 2 years adjusted age, they were not different from the control infants of 600 to 750 g birth... [ABSTRACT FROM AUTHOR]

Abstract. From September 1989 through July 1991, before commercial availability, Survanta (beractant intratracheal suspension), a modified bovine-derived surfactant used for prevention and treatment of neonatal respiratory distress syndrome, was made available to 231 neonatal intensive care units in the United States and Canada under a Treatment Investigational New Drug protocol. Results of this open clinical experience are reported. Investigators could give one dose of Survanta soon after birth to neonates weighing 600 to 1250 g (prevention strategy). Neonates weighing 600 to 1750 g who were not treated at birth could begin Survanta therapy if respiratory distress syndrome developed within 8 hours of birth (rescue strategy). All neonates could receive up to three more doses over the first 48 hours of life at minimum intervals of 6 hours if they met retreatment criteria. Qualifications for enrollment closely matched those used in previous randomized controlled clinical trials. This report includes results from 8168 neonates who completed the study. Treatment Investigational New Drug rates for intracranial hemorrhage, patent ductus arteriosus, pulmonary hemorrhage, pulmonary air leaks, bronchopulmonary dysplasia, death or bronchopulmonary dysplasia, pulmonary interstitial emphysema, pretreatment sepsis, and posttreatment sepsis were less than for treated neonates in the controlled trials and survival was equivalent across studies. Problems with treatment administration were reported with 30.4% of doses, while adverse events were reported in 0.5% of neonates. The results of the Treatment Investigational New Drug protocol revealed no new safety concerns associated with the... [ABSTRACT FROM AUTHOR]

Abstract. To determine if outcomes of low birth weight neonates with respiratory distress syndrome can be improved by the administration of multiple doses of bovine surfactant, we conducted two identical multicenter, controlled trials, and the results were combined for analysis. Seven hundred and ninety-eight neonates weighing 600 to 1750 g at birth who had developed respiratory distress syndrome within 6 hours of birth were assigned randomly to receive either 100 mg of phospholipid/kg of Survanta, a modified bovine surfactant (n = 402), or a sham dosing procedure (n = 396). Neonates whose respiratory distress persisted could be given up to three more doses, with all doses to be given in the first 48 hours after birth. Dosing was performed by investigators not involved in the clinical care of the neonates; nursery staff were kept blinded as to the treatment assignment. Fewer Survanta-treated neonates died of any cause (18.4% vs 27.3%, P = .002), died of respiratory distress syndrome (9.0% vs 20.3%, P <.001), and either died or developed bronchopulmonary dysplasia due to respiratory distress syndrome (51.2% vs 64.6%, P <.001). Neonates who received Survanta also had greater improvement in their oxygenation and ventilatory status from baseline to 72 hours than did control neonates. Survanta-treated neonates were at lowered risk for developing pulmonary interstitial emphysema (18.6% vs 39.3%, P <.001) and other pulmonary air leaks (11.5% vs 25.9%, P <.001). We conclude that multiple doses of... [ABSTRACT FROM AUTHOR]

Abstract. To determine whether multiple doses of bovine surfactant would improve neonatal mortality in very premature neonates, we conducted two multicenter controlled trials under identical protocols; the results were combined for analysis. Four hundred and thirty neonates born between 23 and 29 weeks gestation and weighing 600 to 1250 g at birth were assigned randomly at birth to receive either 100 mg of phospholipids/kg of Survanta, a modified bovine surfactant (n = 210), or a sham air placebo (n = 220) within 15 minutes of birth. Neonates who developed respiratory distress syndrome and required mechanical ventilation with at least 30% oxygen could be given up to three more doses in the first 48 hours after birth. Dosing was performed by investigators not involved in the clinical care of the neonates; nursery staff were kept blinded as to the treatment assignment. Cause of death was determined by a panel of three independent, board-certified neonatologists after blindly reviewing case report forms and autopsy reports. Fewer Survanta-treated neonates died of any cause (11.4% vs 18.8%, P = .031), died of respiratory distress syndrome (1.9% vs 15.6%, P < .001), and either died or developed bronchopulmonary dysplasia due to respiratory distress syndrome (39.5% vs 49.1%, P = .044). The incidence of respiratory distress syndrome was also lower in Survanta-treated neonates (28.0% vs 56.9%, P < .001), and the Survanta-treated neonates' oxygenation and ventilatory status were improved significantly at 72 hours. Survanta-treated neonates were also at lowered risk... [ABSTRACT FROM AUTHOR]